Telomeres and longevity – questions from readers

The following questions were sent in concerning telomeres, telomerase, TA-65 and the Life Length assay as offered in the U. S. by adltests.com.

Question 1:  Is the database mainly constructed in the US?

Answer:  The database is worldwide but the bulk of the database comes from the U.S. The only lab currently offering the Life Length assay in the U.S. is adltests.com.

Question 2:   Why is it that the average percent of short telomeres is roughly the same, and not rising, for the deciles 31-40, 41-50 and 51-60 of the results report?

Answer: The percentage of short telomeres required to drive disease/dysfunction is the same no matter what the age range of the participant. There is a threshold within each cell thus generating “old cells” that need to be removed in any biologic age population. Similarly “young cells” can exist in any age population as well. The threshold that confers senescence or apoptosis (self destruction/removal) of the cell is not dependent on chronologic age solely. It is dependent on number of replications, accrued damage (oxidation) and measures one might take to minimize or reverse that damage. The so-called Hayflick limit is an idealized maximum number of cellular divisions that can occur in more or less perfect conditions and implies that, no matter what, the cells will continue to “age” due to telomere loss.  The actual human Hayflick limit is now 122 years as witnessed by Jean Calumet, the oldest documented human being who died fairly recently. It is important to understand that the Life Length assay is the only one reporting percent of short telomeres at this point, and one can have “normal” mean telomere length with a low or high percentage of short telomeres. The latter changes the meaning of telomere testing completely, as most people with “normal” mean telomere length have no idea if their cells are old or young biologically because this critical piece of information is missing.

Question 3:   Have you found any evidence that the average percent of short telomeres may vary across different ethnic groups or by gender or any other grouping factor?

Answer:  Since the Life Length Assay is still new I don’t think I can honestly answer that question until the database grows to a much larger size. Basing the answer on previous technologies may lead to false conclusions since they do not yield this kind of data. But the short answer and the one that is currently (and I stress the word “currently”) accepted is that there may be such ethnic and more likely gender differences. For instance there is a small subset of Ashkenazi Jews that have allelic “over expression” of telomerase which confers longer telomeres and longer life/healthspans.

But for most of us epigenetics which while heritable is also mutable is the most likely factor in telomere length and lifespan. Things like nutrition/supplementation stress handling, sleep, exercise habits etc are still far more likely to contribute to telomere health and length for the general population.

Question 4: Has there been any empirical test of the telomere hypothesis, i.e. that individuals with low percentages live longer?

Answer: There have been many such studies and it is generally agreed upon in the “telomere community” that, based on the studies, this is an immutable fact. Similarly evidence exists to show improved health parameters as well in humans mouse and human cell lines although this is a different line of questioning.

You will find large scale studies to validate that longer telomeres equate to longer life starting here.

You will need to scroll to several pages to get the ones that specifically answer that question. In addition due to the failure of Calorie restriction over expression of telomerase to lengthen telomeres now exists as the ONLY method of extending life span in higher mammals. Maria Blasco was able to demonstrate a single isolated treatment with telomerase added 25% to the life span of middle aged mice and 13% to old mice. Her study on short telomere rate increase can be found here.

Please note: until the pharmaceutical industry jumps on this bandwagon, no one will have the money to do the study we all want: a longitudinal study of humans with random selection (not twins, etc.) in diverse populations over many decades to see the effects on human longevity when we turn on telomerase with supplements or other avenues. In other words “Can we make people live longer and healthier by lengthening their telomeres or more specifically decreasing the number (%) of short telomeres?” Even then it is likely they will not do that study; rather the answer will come from several generations of clinical observation and research into the results of drug therapy for telomerase when that actually happens. Surprisingly, human longevity and healthspan are not even on the radar of most governments!

TA-65 is currently the only telomerase activator that has been 1) evaluated for safe human consumptions 2) Proven to work in human beings. No other compound has that data.

One thing we know at this point is that, statistically speaking, diseases are fewer and lives are longer in those blessed with healthy long telomeres.

Please keep in mind one can still be hit by a bus!!!

Dr Dave

Telomeres, Chronic Pain and Accelerated Aging

A new study has linked the pain syndrome known as Fibromyalgia to shortened telomeres (biologic time clocks). I have already begun to get emails asking me if TA-65 will help this, due to the most recent information.

Before I answer that question, a little background is in order. As you hopefully know already, the telomere is a small segment of non-coding DNA at the end of the chromosome.  Originally thought to be junk, it was found to be intimately involved in “cell cycle” regulation.  Things like the ability of the cell to replicate and make more of itself, as well as many functions associated with cellular (and organismal) aging, were eventually tied to telomere length.

Things like overall longevity, healthspan, and the associations of all kinds of diseases of aging, including heart disease, Alzheimer’s, cancer, depression and stress, were seen with shortened telomeres*. In some cases, they are clearly biomarkers of aging and disease. In some cases, they drive aging and disease.

In all cases that we know of so far, longer, healthier telomeres are associated with improved prognosis in the middle and older age groups that get these diseases. And of course, they are part of living longer.  In populations that have “allelic variations”, which are basically mutations, in most cases that express increased amounts of telomerase (the enzyme that lengthens telomeres), there is a significant likelihood you will find the extremely long-lived and more healthy individuals.

Fibromyalgia (FM) is a vexing, chronic pain syndrome that seems to have many causes and just as many treatments. In addition to antidepressants and numerous dietary and exercise prescriptions, there is a growing feeling among many people who have treated it, that it is a mitochondrial disorder.

The mitochondria, the cellular powerhouses, appear to become dysfunctional in this syndrome and facilitate pain transmission via the effects of the toxic metabolites they produce and can no longer handle. Basically, a free radical trigger like oxygen or nitrogen accumulates and is not appropriately balanced or handled, and a series of events result that cause pain transmission to occur at a lower threshold.  The attendant illness, Chronic Fatigue Syndrome (CFS), is even easier to explain by this mechanism, since decreased mitochondrial function is associated with lowered energy output and fatigue.  This is what you see as your parents age and slow down as well!

If you live in Europe or Japan and have CFS or FM and seek treatment, you will most likely receive Coenzyme Q10 in its reduced form, in doses of around 400mg a day as starters.  This is also the dose I give my elderly patients complaining of fatigue (200mg 2X a day or 400mg at once). Here in the US, most doctors avoid using supplements for treatment, still clinging to anti-depressants and lifestyle modifications, which if they work at all, are the result of the person slowly healing themselves by avoiding excess energy expenditure and healing their mitochondria!

So, the question comes around to treatment.  I always started with Coenzyme Q10 and then moved into B Vitamins.  When TA-65 came along much later (2009), its energizing properties were of great use to some of my patients with CFS.  I never did an official study though, and it was not part of our soon-to-be-released TA-65 survey questions.

Still, the telomere seems to have some major sway over mitochondrial behavior.  Dr Ron DePinho, now at MD Anderson Cancer Center, has shown the likely involvement of telomere length directly affecting mitochondrial energy generation, biogenesis, and mutation rate.  So, it’s highly likely that anything that improves the health and length of the telomeres like TA-65 should be of great help in CFS.

The other thing to keep in mind is the modification of the way the body deals with stress.  Our Nobel Laureate, Liz Blackburn and her colleague Elisa Epel, have done several studies that show telomere length correlates with perceived stress levels.  Others have shown the association with depression.

The key word here is “perception”. We all know people who have had what most of us would term a hard life, physically and mentally, but live long and happy lives. We all know people who fall apart at the slightest provocation and respond poorly to minimal stresses. Often referred to as a person’s “nature” (happy, sad, stoic, etc), these correlations with biologic changes have made doctors uncomfortable since they are not easily quantifiable. Liz Blackburn used urinary excretions of stress metabolites to give this kind of perception a quantifiable and valid number. They also found cortisol drops over time, instead of rising, giving credence to the concept of “adrenal burnout”. Lowered cortisol or inappropriate cycles of cortisol secretion can allow the chronic, low grade, self-targeting inflammation we know is associated with many diseases of “aging” to rise and run rampant.

If you’ve gotten this far in this blog with me, then you will probably not be surprised by the following comment: Candice Pert, Bruce Lipton and Abraham Hicks are right! How you handle things and what you think about has a lot to do with what goes on inside your body!!!

I am now in my 4^th year of taking TA-65. There have been a few times when I stopped it for a week or two. No More! I cannot afford anything less than maximum drive and energy in my life!

Doc

*One final comment on the article:

Since the article mentions “biologic age”, I would hope the method used to determine telomere length included both median and percentage short telomeres, since the latter is really the only assay that can comment on biologic age. Short telomeres drive aging and cellular dysfunction and currently the “cut off” is in the 3KB range. Short telomeres are unseen in typical QPCR and FLO FISH assays, which also have poor accuracy and reproducibility. They can easily be at a critical value, buried within the data of median telomere length and often do not correlate well with median or mean telomere length at all. The veracity of small studies especially, could be markedly improved by using HT-QFISH technology developed by Maria Blasco that has been commercially available for over three years now. In its absence, the findings of any telomere study that is looking at individuals in small numbers, is questionable. The median telomere length is also obtained by this technique and it correlates well with other technologies.

If you are serious about telomere length measurements for your own personal use, then go to ADLTests.com and get the life length assay done. If you are already on TA-65, any future telomere tests you do should be done with this test.

Reference quote from the article which appeared in Anesthesiology News on-line: “Patients were categorized as experiencing high levels of pain (BPI ≥5; n=30) or lower levels of pain (BPI<5; n=31). Women who scored at least a 5 on the BPI—the cutoff for “high” levels of pain—were more likely to have shorter telomeres regardless of their chronological age (F=5.39;P=0.024). “This difference,” Dr. Hassett said, “represents approximately five years of aging.” That estimate is based on a previous study that linked the deterioration of telomeres to time (Proc Natl Acad Sci USA 1998;95:5607-5610).”

Fish oil – Failure by design

A few months ago I wrote a blog/newsletter entitled “Don’t Swallow It!”

It was lamenting the lack of a BS detector on the internet and how easily factoids can spread misinformation. Today’s little gem fits right in with that theme.

The latest round of “Fish oil No Good for Heart Disease” studies was published this week by the prestigious New England Journal of Medicine (NEJM).  The NEJM has long been considered the pinnacle of medical journals the world over. It is of course solely supported by Big Pharma advertising.

Like the other big Journals, JAMA and the Archives of Internal Medicine, it maintains an “anti-supplement” stance, rarely publishing anything positive about anything that is not a Big Pharma drug.

Since most allopathic doctors do not apply critical standards to what is published in these journals, the word of these journals is gospel.

Not surprisingly the latest “Fish oil no Good For…” study will get a lot of air time and be virally spread on the internet with even less critical thinking and even more acceptance from the general populace.

One site that repeats internet nonsense is already saying, “The pendulum is swinging away from fish oil!”

While I don’t normally bother with this because it has been coming and going for the past 10 years, I will admit there really seems to be an “anti-fish oil” campaign out there.

The “Just eat fish” crowd has conveniently forgotten the issues of lead, mercury, arsenic, cadmium and plastic-derived xenoestrogens and toxins that are found in most oily fish in quantity. A few have even suggested that the “other oils” in fish, the stuff that is not EPA and DHA, have value. They sure do!

They are valuable for calories! They make no contribution to the biochemical pathways and are otherwise non-essential, however.

Getting back to the study aspect of things, I’ve said it a thousand times but I am forced to say it yet again.

Any study that does not…

1)      Use a dose of fish oil that actually matters

2)      Does not measure blood or tissue levels (the finger stick Ideal Omega test is soooooooooooooo simple but they don’t bother!)

3)      Attempt to achieve the ratios of Omega 6 to Omega 3 that parallel the populations that have almost NO HEART DISEASE compared to ours. (It’s in the neighborhood of a 10 fold reduction).

…IS DESIGNED TO FAIL

So let’s look at the particulars of the study:

A)     Dose?  1 gram.   The study population was Italian, clearly a Waster diet based group.  No, they were not on the “Mediterranean Diet”, a Health/Marketing concept created by Dean Ornish. They were clearly eating pasta!

B)     “Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction.”  In other words, they were ticking time bombs waiting to have their heart attacks. Their doctors already knew they had heart disease in many cases.

C)     What was the type of fish oil administered? It does not say; so it could easily have been a non-concentrated “natural cold pressed triglyceride” fish oil, which provides only 30% EPA and DHA. I need to try to find this out because it makes a huge difference.

Why? Because they may have actually been only getting 300 mg of the active oils for cardiac disease prevention. You have heard me say the average Westerner needs at least 6 grams a day to fix their Omega 3 deficit and balance out their excess Omega 6’s.

D)     No levels were measured in these people – if they were, they would not have even scratched the surface with the dosages they chose to give people.

E)      The GISSI Prevenzione study also done in Italy over a decade ago using 2 to 3 grams a day of the highly concentrated ethyl ester form, like mine, (still an under dosage but better than this one) showed a far different 35% reduction in Cardiovascular Death.

Two other things of note: The placebo was Olive oil, which is appropriate since Olive oil is Omega 6 dominant (21 to 1 Omega 6 to Omega 3).  Next, they had to fiddle with their chosen end point: “At one year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes.”  This kind of last minute post study fiddling makes the entire study questionable in my opinion!

At least this was a study, however, and not a “meta analysis” – a computer generated file based on cherry picked data that can prove anything the authors want without spending more than a few dollars in computer time and many hours of doctoral candidate slave labor!

So what should this study have been titled?

Here’s mine:

UNDER DOSING WITH FISH OIL IN A HIGH RISK POPULATION DOES NO GOOD TO PREVENT THE PROGRESSION OF HEART DISEASE

Frankly, this kind of study, done in an era where the data already exists for both primary and secondary prevention with Omega 3’s, constitutes malpractice in my opinion.

Also, I am not insensitive to the fact that my study title would probably not get many people to be interested, so here is another one which might intrigue the reader more – something you have to do for a sound bite society.

I would call it the Educated Authors Trying to Suppress Healthy Interventions Trial. You may be aware it is customary in medicine to use the first letter of every capitalized letter in a trial to create an acronym for the trial’s name. I will leave you to that.

I will also comment that acronym is pretty much my opinion of this study, which was designed to fail, adds nothing to our knowledge base and will undoubtedly contribute to the misinformation database out there in cyberland.

Finally, I will say that if you actually do figure out the acronym based on what I told you above, you might anticipate a new Meta analysis that will tell you this practice is actually healthy for you! I doubt it will make it into the NEJM, however, unless there is a Big Pharma drug somehow involved.

Don’t swallow it!!!!

Doc

 

Reference articles:  n–3 Fatty Acids in Patients with Multiple Cardiovascular Risk Factors

The Risk and Prevention Study Collaborative Group

N Engl J Med 2013; 368:1800-1808 May 9, 2013 DOI: 10.1056/NEJMoa1205409

J Toxicol Environ Health A. 2007 Nov;70(22):1897-911.

Heavy metals in Pacific cod (Gadus macrocephalus) from the Aleutians: location, age, size, and risk.

Burger J, Gochfeld M, Shukla T, Jeitner C, Burke S, Donio M, Shukla S, Snigaroff R, Snigaroff D, Stamm T, Volz C.

Source

Division of Life Sciences, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08854-8082, USA

“If a subsistence fisher from one of the Aleut villages ate one meal of cod per week for As, or one meal per day for Hg, they would exceed the U.S. EPA reference dose for As and Hg” As is Arsenic, HG is mercury!

Stem cells, telomerase and Immortality

Stem cells are often referred to as the “parts bag” of your body. When part of your body is damaged, there are two main avenues of repair – somatic cells and stem cells.  Somatic cells are cells that are already at their final stage of evolution.  Examples are mature heart, skin, liver and gut cells. These cells are what they are and cannot be anything else.

Stem cells, on the other hand, retain some or most of their ability to “be anything”, depending on how far along they are in their developmental cycle. The most undifferentiated stem cells are the embryonic types that form soon after you are conceived. These give rise to every other cell in your body. They are known as “totipotent” because they can become anything, cell-wise. No one knows how many, if any of these embryonic cells are around in adults, but my guess is there are at least a few.  As we mature, stem cells assume general identities like neural, mesenchymal and so on. This means they can become lots of things, within a family of tissue, like circulating cells in the blood, connective tissue, like fat cartilage and bone or neural tissue, like nerves, brain and some endocrine organs.  These are called pluripotent, because, while they cannot become any cell, they can be lots of different cells within their overall cell type.  It is from these pluripotent stem cells that most of our somatic cells come from.

One myth that persists is that stem cells are immortal and have lots of telomerase expression. It’s true that they have more than the average cell, which is basically zero, so more is not a lot more than that! As stem cells go down the line from totipotent to pluripotent, to actually committing to being some specific cell type, they lose telomerase activation, making them live shorter lifespans.  When they get to being somatic cells (the last step), telomerase is shut off.

Recently, it was found that defective expression of telomerase leads to premature stem cell aging.  That should be no surprise, based on what I just told you.  Another fact – long telomeres are required for healthy stem cell differentiation, as well. So, telomerase plays a role in keeping your parts bag full and making sure the parts get delivered wherever they are needed.

I am now in my 4^th year of taking TA-65 and I am 100% sure it is affecting my stem cells in a positive way. While no one has yet done stem cell assays on this product, the improvements in health documented by my clients that use it and my own benefits, could not be possible any other way.

I should also mention the skin is the largest repository of stem cells in the whole body. This is why it may be so responsive to our stem cell activating serum RG-Cell.

That gives you two unique ways to improve the stem cell telomerase connection. Growing younger is getting easier and easier!

Doc

Why is Co Q so important for your telomeres?

We got this question through our book site.  The answer, of course, is in the book reference section, but I have long ago given up on people doing anything more than wanting us to do all the work for them!

“In your book, under ‘why is Co Q10 so important,’ you state, ‘some studies that used various forms of Co Q10 suggest that it can actually stop shortening altogether.’ Where can I get this info?” – R

Hi, R. In every cell in the human body, there are many small powerhouses called mitochondria. The purpose of the mitochondria is primarily to burn fat and oxygen (think of a carburetor that burns air and fuel, with fat being the fuel). The source of fat is a combination of dietary fats, carbs and proteins that are all funneled through specific intermediates, into these powerhouses.  Energy is released in stepwise fashion, down a cascade of energy donors and acceptors so that ATP, the ultimate energy currency of the cell is generated.  In the mitochondria, there are 5 major energy exchange complexes named I-V. The very first and the one most susceptible to damage, is the one that relies on reduced Co Q to accept and release energy.

Co Q not only accepts the energy, but it buffers the mitochondrion (singular) from the potential oxidation that this energy can cause. For reasons that are not 100% clear, we begin to develop measurable drops in mitochondria Co Q levels around age 40 and this progresses as we age. Ultimately, our mitochondria become dysfunctional and at least two things happen. They begin to trigger other mechanisms that age the cell and march it towards its demise, and they begin to leak free radicals, through their own protective membranes, out into the rest of the cell, which circles back and a) damages the cell and b) triggers more “I’m getting old” signals in the cell.

The combination of all of this is intimately involved in how fast the telomere shortens and of course, the telomere then can activate other signals that say, “This cell is getting old and needs to die, or be removed from the active cell pool”. Finally, telomere length also accelerates the aging process of the mitochondria by accelerating the generation and leakage of free radicals from it, which causes internal damage to the cell and to the mitochondria.

This is a textbook worth of material in one paragraph, but it gives you an idea of the vicious cycle of telomere/mitochondrial aging as we understand it, at this moment.

Bottom line: the use of reduced CO Q10 ( look for ubiquinol, not ubiquinone) can slow down and in some cases, reverse this decline and help save the telomeres from this type of “internal” free radical damage. Along with Fish Oil and the Telomere Edge Packs, it’s a great way to support the actions of TA-65.

Thank you for this interesting question!

At least this one was interesting and this person seemed genuinely interested. Lots of people write in with “accusatory” questions that are really them venting their own personal agendas. I welcome genuinely interested, open minded people like “R”!

All the best,

Dr Dave

My Favorite Telomere Scientist

Photo credit: SHA.com

I know a lot of amazing people in the telomere field. I have been honored to meet, speak and learn from all of them. But my favorite, as you may already know, is a young lady named Maria Blasco.  I like Maria best for a bunch of reasons, not the least of which is she “gets it” when it comes to the purpose of her telomere research. She may eventually become very wealthy because a drug company may come along and buy her inventions and discoveries.  She may become famous because of her work and may even get the Noble Prize one day.  She is certainly revered in her home country of Spain, because of her work and her role as the Director of the Spanish National Cancer Institute. And I am personally eternally grateful for the many hours of her time she spent with me, both in person and on the phone, because of my intellectual curiosity and of course the current book on the topic I am writing.

But, the reason she does what she does is because she is not afraid to extend the healthspan, lifespan, and quality of life of human beings – like you and me.  She gets it! So many times people lose track of that simple fact. Scientists, doctors, healers of any kind need to be reminded: the end point of your work is the betterment of humanity!

I know Maria knows this.

On March 22nd an SHA seminar about anti-aging entitled “The keys to a long healthy life” included renowned scientists like Dr. Maria Blasco Marhuenda, Dr. Gloria Sabater and Dr. Vicente Mera, discussed about the latest advances in telomere and telomerase research and its application in areas such as rejuvenation, anti-aging for a life extension and cancer prevention.

Obviously telomeres were the topic of discussion, but if you don’t know what a telomere is:  Telomeres are the ends of chromosomes, DNA coding regions whose length determines the biological age of our cells and how long our cells can live. Furthermore, our biological age can ONLY be measured by an analysis HT Q-FISH test www.adltests.com, in the U.S. This is the only test that gives both average and percent of short telomeres, which allows for a determination of your biologic age.  Chronologic age is how many birthdays you’ve counted.  Biologic Age is how old your metabolism and cells actually are, or how old your body really is.

You can decrease the loss of the telomere segment by lifestyle modifications and some supplements like Fish Oil and Co Q10 (ubiquinol not ubiquinone!). But, you can only lengthen the critically short telomeres that determine your true biologic age by using TA-65. At that conference, Dr. Blasco certified that there are some food supplements such as TA-65 that activate telomerase and contribute to natural rejuvenation and life extension without causing cancer.

What is said here is as important as what is not said. Where are the other so-called Telomerase Activators in the speech?

HMMMM!

Here’s to long telomeres!

Dr Dave

My feelings about salivary telomere testing

I published this in response to a blog touting the benefits of salivary testing from a company called TeloMe. I will use the same phrase I did when comparing the efficacy of other telomerase activators to TA-65. It went like this, “How much will people spend on something worthless to “save money”?  Answer: About a hundred bucks.

Here is what I wrote in response to that blog.

Sir, there are a few things that need to be addressed in your blog.

First, the analogy between 23andMe and TeloMe is stretched, because 23andMe measures genes, not telomeres. The accuracy and reproducibility of the salivary genetic testing is improved when the gene is fairly large. In most cases, the genes commented on by 23andMe are in excess of 200,000 base pairs.

The average newborn has a telomere length of 10,000 base pairs, the average middle aged adult, 6,800 base pairs – far shorter and far more likely to be misinterpreted by a salivary test, where DNA degradation is inevitable. Most people are not forensic scientists and will not use the careful collection and processing needed to preserve salivary samples.  In addition, salivary cells completely leave out the important WBC component tested in blood telomere testing. You mention immunosenescence. Nothing about salivary testing tells you anything about this.

Next, biologic age can only be interpreted by the percentage of short telomeres present, not by mean or average telomere length. Those values in the individual case are worthless and say nothing of the biologic age. I have seen numerous cases where people had ‘normal’ average telomere length and very different (higher or lower) percentage of short telomeres, which would have been missed by a mean telomere length test. In the same vein, a mean telomere test has huge gaps in accuracy and reproducibility that are not found in HT Q-FISH short telomere testing. In all cases, two or more tests done at 1 year intervals will be much more useful. I would be very curious to see how close your 1 year values will be with this test. If they vary greatly, which is highly likely, the results will be meaningless.

Next, careful what you say about calorie restriction. Like sirtuins and resveratrol, this has been a banner for large amounts of money research dollars and even a society dedicated to its enactment. But the data are extremely thin, as one moves up the biologic ladder from invertebrates to mammalian forms. There are only a very few strains of mice that respond to calorie restriction with extended lifespans.  Recently, Maria Blasco tested the effects of CR on wild type and telomerized mice. CR did not extend lifespan in either. Increasing telomerase expression did. The recent debacle in monkeys, surrounding the horrible diet fed to the controls and the optimal diet fed to the CR monkeys, abrogated any response from CR in what had been the flagship species, to prove the efficacy of CR in higher mammals. Increased expression of telomerase is, at this point, the only broadly applicable way to increase lifespan in many higher species. For it to work the way it does, it must improve mitochondrial function de facto, as well as a whole host of other things, including protein cross linking, sirtuin expression, AGE’s, mutation rates, etc. etc.

The mitochondrial theory of aging is most likely false for many reasons. The simplest of which is that mitochondrial diseases do not present with accelerated aging. Telomeropathies do. Next, the work of Passos and DePinho, in the past 2 years, points out the likely way that short telomere length controls the behavior of mitochondria, which frankly have too few genes that regulate even their own function, to be a true central controller of aging.

While telomere testing varies greatly in price and accuracy, people spend more on their cell phones and TV’s than on an accurate telomere test, that gives them true biologic age and other information. Not a good use of funds. You mention various price points for testing. At this point, there is no good, cheap way to get meaningful information from a cheap test. People are better off ponying up if they want a real answer, or saving their money and waiting until prices on better tests come down. In similar fashion, if you actually want to ‘take a telomerase activator to do something for your telomeres’ you are better off investing in the only product that has a human track record of safety and efficacy, TA-65.

At a most recent conference, Dr Maria Blasco, one of today’s premier telomere scientists, certified that there are some food supplements, such as TA-65, that activate telomerase and contribute to natural rejuvenation and life extension, without causing cancer.

And there you have it, from a person who I would bet on for a future Nobel Prize!

Best,

Dr Dave – author, The Immortality Edge- Wiley 2010.

The cancer doctors were wrong about telomerase activators and antioxidants!

I can’t tell you how many times I heard this from cancer doctors (oncologists): “Don’t give my patients antioxidants; you’ll blunt the effect of the chemo and help the cancer!”

I always found it ironic that, before the cancer occurred and after they had done whatever they did, which in many cases did not save the patient, the person again became “my patient”.

I also found it ironic that, even though these doctors are very bright and well meaning, they somehow forgot that cancer breaks all the rules of normal cellular behavior and that cancer cells do not behave at all like other normal cells.

The same argument has been applied to telomerase activation.  Because 80+% of human cancers hijack telomerase, there is still a prevailing belief that telomerase causes cancer. This is in spite of all the evidence to the contrary. It is also in spite of two of the recipients for the Nobel Prize in medicine saying otherwise, with regards to the now famous case of a cancer in a person taking a telomerase activator.

So, I thought I would tell you about a study that was released about 6 months ago, that showed exactly the opposite, in hopes of changing people’s views about the specific actions of supplements which, like telomerase activators, remain subject to debate, in spite of the research.

I will give you the reference below, but let me sum it up for you here.

1)     Increasing fruit and vegetable intake is an easy strategy to reduce some types of cancer, if not all.

2)     Dietary flavonoids have been found to have anti-cancer effects and chemo protective effects against cancer.

3)     Many polyphenols and flavonoids may work IN CONCERT with chemotherapy agents, to improve outcomes.

4)     The example of a specific dietary supplement with these features is quercetin.

Here is a list of some foods that are high in quercetin:

Brewed, black or green tea

Red Delicious Apples

Sweet Potato

Kale

Watercress

Red Onion

Broccoli

Most berries!

Specifically, ORGANIC grown tomatoes have much higher content than conventionally grown.

Adding these foods to your diet may indeed help you stay much healthier for a ton of reasons. As I look at this list, I see the mainstay of what I eat on a daily basis.

I would be remiss if I didn’t add in fish oil, not for the quercetin, but for the documented effect on cancer!

To your health!

Dr Dave

Reference article: Ann N Y Acad Sci. 2012 Jul;1259:95-103. doi: 10.1111/j.1749-6632.2012.06599.x.

Dietary polyphenols in cancer prevention: the example of the flavonoid quercetin in leukemia.

Spagnuolo C, Russo M, Bilotto S, Tedesco I, Laratta B, Russo GL.

Source

Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy.

Abstract

Increased consumption of fruit and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. We recently demonstrated that the flavonoid quercetin, naturally present in the diet and belonging to the class of phytochemicals, is able to sensitize several leukemia cell lines and B cells isolated from patients affected by chronic lymphocytic leukemia (B-CLL), in addition to apoptotic inducers (anti-CD95 and rTRAIL). Further, it potentiates the effect of fludarabine, a first-line chemotherapeutic drug used against CLL. The proapoptotic activity of quercetin in cell lines and B-CLL is related to the expression and activity of Mcl-1-antiapoptotic proteins belonging to the Bcl-2 family. Quercetin downregulates Mcl-1 mRNA and protein levels acting on mRNA stability and protein degradation. Considering the low toxicity of the flavonoids toward normal peripheral blood cells, our experimental results are in favor of a potential use of quercetin in adjuvant chemotherapy in CLL or other types of cancer.

Fish oil and High Blood Pressure

You know, it’s funny.  You can always tell when something has truly become popular because it begins to inspire negative comments. People are so “in need “of something different that what used to be exciting, positive information is no longer read or paid attention to.  Instead, only the negative press gets attention.

That is how I know that I have basically succeeded in my mission to spread the word about fish oil – something that started over a decade ago.  I just read something else that confirms it.  Fish oil is apparently the most popular supplement in the history of mankind. It’s also the most popular supplement among doctors.

That really makes me laugh when I think of all the abuse I had to take from my colleagues a decade ago. The medical director at the hospital thought I had lost my mind and many of my “friends” would no longer speak to me because I had “gone over to the dark side”.

Now they are all taking fish oil!

So, I was not surprised last week when some scientists at my former alma mater released a paper suggesting that  “the short chain ethyl ester DHA found in some fish oils” might not work the way “natural DHA” does to control blood pressure.  They suggested it might even antagonize the effects of natural DHA and not help blood pressure at all.  Notice they did not say, “It makes your blood pressure worse!”

This of course got translated on the internet to: “Fish oil makes blood pressure worse!”, “Fish oil no good for blood pressure!” and something I see more and more of, “Don’t take fish oil; EAT fish instead!”

As usual, no one actually reads the studies, just the headlines and then they get sensationalized, so here is what you might want to know, if you care about the truth.

1) The study was carried out in genetically modified mice.

2) Mice are an excellent model for studying human diseases, including high blood pressure, especially the effects of drugs on high blood pressure but…

3) Mice metabolize and use EFA’s (essential fatty acids) like DHA and EPA (fish oil’s EFA’s) differently than people do. For instance, since they are pure herbivores, plant-based 18 carbon EFA, as found in vegetables and flax oils, is converted well to EPA and DHA in mice. Not so in people.

Mice also make different end products and store and release those end products in different ratios than people, leading to different effects.  These end products called “autocoids” are derived from EPA and DHA and have as much to do with blood pressure effects as EPA and DHA themselves. This makes the statement embedded in this study – people should be careful about using Omega 3 enriched supplements – extremely far beyond what the data of this study actually showed and basically does a disservice, because the actual data on fish oil and blood pressure is quite positive in most studies.

4) The study only looked at DHA effects, not EPA effects.

So, basically this study took a specific breed of genetically engineered mice, used one component of DHA ethyl ester and caused a stir among the internet, by suggesting that this type of fish oil was not valuable for treating blood pressure, even though it has been proven so many times over in other human population-based studies.

The main reasons for using ethyl ester fish oil and the main reasons I make it are as follows:

1)  The molecular distillation process allows for concentration of the essential fatty acids (EPA and DHA) beyond what is naturally found in fish.

2) The same process, if applied diligently, can clean up the fish oil to parts per trillion in toxins, which basically means no toxins are detectable. This means you can take it for life in the large doses most people need to improve their Omega 3 ratios, without fear of poisoning.

3)  The removal of some of the more saturated portions of fish fats means you are less likely to get oxidized product. We know that oxidized fats of any kind are not good for you!

4) All of the biggest studies in human populations, like the Italian GISSI studies, with a cumulative enrollment of over 50,000 patients, used this form of fish oil.

5) Ethyl Ester fish oil is more slowly absorbed and gives “even coverage” of anti-inflammatory autocoids (the stuff that is made by cells from fish oil) reducing heart attacks over a 24 hour period, not just close to the time it was taken. This became apparent when one of the peak times for heart attacks; 4 to 5 AM was flattened out in the analysis of the GISSI studies I mentioned above.

6) This very same behavior of autocoids from fish oil is one of the main reasons the oft used “krill is better because it’s a phospholipid” argument is nonsense.

I could go on and on and get very deeply into the actual science of how cells and the body use these absolutely essential biochemicals in fish oil, but I think you get the gist.

Somehow, they never ask me to explain this stuff!

Don’t forget to take your fish oil every day!

Doc

New Study on Telomeres Answers some Huge Questions

A couple of questions have been nagging at those of us who study telomeres and telomerase closely.

The first is – what is the correlation, if any, between tissue types? Typically we measure telomere length in the granulocyte line of White Blood Cells. These cells are typically responsible for fighting off viral infections and the immune surveillance against cancer.  How do the lengths that we measure correlate with other tissues? Limited studies have pointed to a good correlation with telomere behavior but not necessarily length. In other words, when someone has short telomeres in one type of tissue they will have short telomeres in another type relative to that type.  The numbers will not be the same but the tendencies will be.

Next, why is there variation in the speed at which telomeres are lost? It seems most of us lose a lot of telomere length relatively early in life and then sometime around late-middle age we slow down that loss. In old age there is a steady slow loss of telomere length unless you provoke it.

Finally, what is the major stress for telomere loss and how does it explain what happens to us when we get sick and/or age rapidly?

A most recent study has pointed to the following very important answers:

1)      The White Blood Cell Line we measure is probably the most important for two reasons. First, it does indeed correlate well with other tissues’ telomere behavior even though the absolute lengths are different.  The white blood cell line is capable – and actually required – to have tremendous ability to replicate because of the short lives of these cells and their high demand. This results in a line of cells that actually have the shortest telomeres among the cell types tested. The other lines had increasingly longer telomere lengths in this order: skin, fat, muscle. Once again it is important to understand that once you have established a relative “normal length” for the telomeres in each specific tissue type, you do see a correlation between “long” or “short” telomeres in each tissue type, basically making the White Blood Cell (WBC) measurement a reasonable surrogate for what is happening elsewhere.

2)      The variation in the speed of loss during life seems to depend on the need for each tissue to replicate.  The WBC are constantly replicating their entire volume throughout life. Early in life the amount of cells actually has to grow to meet the growth of the person from infant to adult. All the while there are immune challenges that have to be met for that child to reach a healthy adult state. That means lots of replication. Muscle cells, on the other hand, need far fewer replications to go from childhood to adult. They do not die off at nearly the rate WBC’s do and once they are there they simply grow larger rather than replicate to make more cells.  Skin cells turnover a lot so they behave more like WBC’s and fat cells behave more like muscle. The variation in the need for replication in each tissue accounts for the rapid telomere loss early in life and a slowing down later in life, since once the person is mature, only maintenance is required.

3)      The major stress for telomere loss is replication but here is the absolute super important fact. It affects the stem cells most. Recall stem cells are the parts bags we use to rebuild our bodies. Stem cells have only a small amount of telomerase (the enzyme that lengthens telomeres) to keep them young for a time, but they do age like other cells as we get older. This means they cannot keep pace with the need for replication and we start to age and get sick because of the combined loss of non-stem cell mass (typical cells) and the loss of our repair parts (stem cells).  When damage exceeds repair we get into trouble and age and get sick.

A couple of very interesting things also were backed up by this new study. First, inflammation is absolutely critical in accelerating the loss of both our typical cells and our stem cells, especially in the WBC line. Since they are part of the immune system, low grade inflammatory stuff like obesity, sedentary behavior, poor diet, smoking, lack of sleep and stress all accelerate their demise and burn out the stem cell lines. This is particularly true if you have high Omega 6 levels and low Omega 3 (fish oil) levels. So take enough fish oil to make a difference!

Next, certain specific behaviors can accelerate telomere loss in tissues that normally don’t see a lot of it.  We know that the cartilage cells in basketball players tend to have short telomeres.  The repeated jumping undoubtedly stresses the replication capacity of the stem cells of those tissues and burns them out faster. Similarly the muscles of long distance runners have shorter telomeres for the same reason – burned out stem cells.

There are two other things you can intuit from these findings. 1) Things that stimulate telomerase not only benefit regular cells but, in particular, stem cells.  This would mean that the natural telomerase activator TA-65 is a true stem cell stimulator. I’ve often said it has to be, but now we know why.

On the flip side, it is already known that EGF-1 one of the main ingredients in RG-Cell Super Stem Cell Activator have been shown to be telomerase activators. We are not making this claim for RG-Cell yet since it has not been specifically tested, but it is highly likely.

In summary, the above strongly support Fish oil, TA-65 and RG-Cell as the ultimate anti-aging combination!

Big Stuff!!! And speaking of Big Stuff, keep your eyes on my newsletters for a huge announcement any day now!

Things are getting really exciting!

Doc

Reference study: Telomeres shorten at equivalent rates in somatic tissues of adults

• Lily Daniali, Athanase Benetos, Ezra Susser, Jeremy D Kark, Carlos Labat, Masayuki Kimura, Kunji Desai, Mark Granick, Abraham Aviv, Affiliations Contributions, Corresponding author

Nature Communications

4, 19 March 2013

How to use a Telomerase Supplement

As one of the “original cast and crew” using TA-65, I get a lot of questions about how to specifically use the product.

Here is a breakdown with special attention paid to age at the time of starting TA-65:

• 250 units (1 capsule daily) is efficacious for healthy adults in their 40′s or 50′s. Also, 250 units can serve as a maintenance dose for older people who have been taking higher doses of TA-65 for several years and want to continue on a reduced cost program. Clients who took this dose were shown to have increased short telomere length and significantly improved immune system function. There are also anecdotal reports of increased endurance and other benefits.

• 500 units (2 capsules daily) has been proven to lengthen short telomeres, restore the immune system, and improve other important bio markers. Anecdotal reports included increased energy, endurance, vision improvements, sexual enhancement, and more. This medium strength dose is recommended for people who are generally in good health and want to be proactive in longevity and healthy aging. Many people in their 50′s or 60′s fall into this category. There have been anecdotal reports of hair regrowth and decreased/or reversal of grey hair. I can attest to the hair growth since just about every male and some of the women in my family are pretty much bald by the time they hit 50!

• 1000 units (4 capsules daily) This is considered the FULL DOSE and is recommended for clients who are:

1. Over 55 years of age, or
2. Are of any age and have measured their telomeres and found them to be short, or
3. Have reason to believe that strengthening their immune system would have particular benefit.
4. Are of any age with a major illness or risk factor such as diabetes, heart disease, strong family history of those or other diseases of aging such as Alzheimer’s. It is expected that this dose will give an increased benefit over the lower doses (although not a proportional benefit). Study subjects experienced lengthened telomeres, restoration of weak immune systems, bone density improvements and other important bio marker improvements which usually decline with age. Anecdotal reports include energy increase, endurance, cognitive improvements, improved vision, sexual enhancement, and an overall feeling of well being. I have personally been on this dose for 4 years now, as has my 87 year old mother.

It is expected that this dose will give an increased benefit over the lower doses (although not a proportional benefit). Study subjects experienced lengthened telomeres, restoration of weak immune systems, bone density improvements and other important bio marker improvements which usually decline with age. Anecdotal reports include energy increase, endurance, cognitive improvements, improved vision, sexual enhancement, and an overall feeling of well being.

Since telomere loss starts more or less as soon as you are conceived, some people have asked about starting their kids on it. I do not recommend that as there is no data. Similarly, if you are pregnant or nursing, I would not take TA-65 since there is no data on it during these times.

Of interest: Pregnant mothers who undergo stress during pregnancy DO PASS ON DECREASED TELEOMERE LENGTH to their offspring. Those kids may also experience accelerated telomere loss during their adult lives, suggesting that the intra uterine environment has a significant influence on how kids age!

At this point the youngest person I have on TA-65 is 26 but they have a documented Life Length Test that shows both a higher than average percentage of short telomeres equating to a biologic age some 13 years older, as well as a mean telomere length that is shorter than predicted. All told, this person may have a defective telomerase gene. This is not common and I only have one other person in their 20’s on TA-65.

A quick note about when to take TA-65. The standard recommendation is on an empty stomach in the morning. Sometimes you have to make adjustments though and take it in the evening. My overall recommendation is that TA-65 be taken when your stomach has been empty for a minimum of 30 minutes, regardless of the time of day.

Be aware of the “energizing” effect of TA-65, which can cause some problems for people sleeping if they take it too late at night.

I hope this helps all of you who are using the product to get the most out of it!

Best,

Doc

Natural Telomerase Activators

This past week, Geron just announced a successful test of a telomerase activator in mice. The goal of this activator is to reverse lung damage caused by a telomere dependent disease known as IPF, idiopathic pulmonary fibrosis.  The word idiopathic does not mean the doctors are idiots and can’t figure it out; it means “cause unknown”. Telomerase activation in these mice did indeed reduce the damage to lung tissue and was safe for use.

Undoubtedly, this will eventually be trialed in humans, since IPF mortality is 50% in 5 years, making it a very certain death sentence for most of the people that have it. The new compound is also undoubtedly going to be marketed as a drug rather than a supplement, since this will be where the big “payday” is.

Now, a couple of things to understand based on my knowledge of the field.

1) This new drug is actually made from something either identical, or extremely similar to TA-65 as a starting point. And this new drug turns on telomerase to a degree that seems to be right in line with that of TA-65, based on potency data I have seen in various studies, although time may prove it to be more potent.

2) The new compound, while not “natural” in the truest sense of the word, does have a natural TA-65-like compound as the starting point so it comes from a natural origin.

3) This is the first of what will hopefully be many new compounds based on TA-65, modified for disease use.

A few more other things to understand:

1)      Reversal of cell damage is the first step to attaining even “normal” longevity.

2)      The degree to which we turn on telomerase is the degree that we transition from health maintenance to longer, healthier lives.

3)      TA-65 has been studied for over 8 years now in human populations, including HIV infected people. It reverses many of the biochemical markers of aging, including inflammation and immune incompetence and it has done so in every model it has been tested in.

4)      My clinical experience with TA-65 as one of the early adaptors has been universally positive. I am on it personally for 4 years now, as are my immediate family. None of us will stop it, unless and until something better with HUMAN data comes along. As of this point, there are no other compounds on the market with the science, the studies and the proven efficacy of TA-65.

5)      There are some natural compounds out there that have shown in LAB DATA, only to turn on telomerase. This list would include all of the MLM level products of which there are 3 that I know of.

Here are the others:

Carnosine in high doses

Milk thistle

Glutathione

Human Growth Hormone

Male and female sex hormones (testosterone and estrogen)

Co Q10 (note PQQ has NOT been tested)

Tocotrienols

Vitamin D

Astragaloside IV

As I have said before, if you can afford the best for your health, then do everything you can to help keep your telomeres younger.

As of this moment and for the past 4 years running, TA-65 has to be at the top of the list.

Doc

P.S. If TA-65 is out of your price range check out the ingredients in my Telomere Edge Pack.

Many people use it until they can afford TA-65 and many people who are on TA-65 continue to use it as a supplement for healthier telomeres.

Short telomeres are associated with decreased cancer survival

At the end of 2010, one of my least favorite journals, JAMA, published a very important and surprisingly forward-thinking (for them) article on telomere length and cancer.  The study was a large Meta-analysis of telomere length and the likelihood of getting cancer.

People were divided into “quartiles” according to telomere length. Basically, this means there were four groups, each with successively longer telomeres. Again, not surprisingly, they found the shortest group had a 500% increase in cancer incidence, versus the longest group.  The other two “middle” groups were in between, with each successively lengthening in those groups, having a lower chance of cancer. Finally, the types and aggressiveness of the cancers were noted to be much worse in the shortest group.

In summary, the shorter your telomeres, the higher the likelihood you’ll get cancer and the worse it’s likely to be.

A recent Danish study showed an association between post-cancer survival and telomere length, once again in quartile fashion. Those with the shortest telomeres were the most likely to die and those with the longest, most likely to survive.

You may wonder why I am harping on telomeres so much.  The simple answer is that not everyone is convinced they are important.  Generally speaking, the status quo is hard to change.

I got a typical email from a friend of mine that pretty much says it all.

“Hi Doc,
Hope all is well. I haven’t talked with you in while – are you still traveling around, speaking on telomeres? It’s funny… you were the first one I ever heard bring that up, now I’m reading about it everywhere. I just saw another article on it the other day…cool stuff!  Lou”

Yes, my friend, I am still out there beating the drum, fighting the naysayers and trying to help people live longer and healthier.

So, when people ask me what to do about their telomeres, I give them a 4-step process, which is listed in order of cost, since many people still value cellphone minutes above their health. You can pick and choose to do none, some, or all of it based on your priorities.

• Read The Immortality Edge.
• Take 6 Fish oil caps a day and test your levels. Adjust as needed to get to a healthy Omega 3 level.
• Take the AM and PM Telomere Edge Packs.
• And the crown jewel of them all is TA-65. While it is the most expensive on the list, it’s also the most proven and most potent – hands down.

Over the coming years you will see the following: More and more evidence that telomere length is directly related to lifespan and healthspan. Occasional nay-saying articles that question or “refute” those findings. This type of article will be far fewer in number than the positive ones, but will get more press, because no one wants to hear another repetitious finding – they want controversy, because controversy sells. More and more “telomerase activators” with no proof of activity, or scant proof that is not repeated. More studies about the efficacy of TA-65.

How do I know all this? No, I am not clairvoyant, I have simply seen and heard it all before with Fish oil, the greatest supplement discovery of the last century.  TA-65 is the greatest supplement discovery of this century so far, so it stands to reason history will repeat itself.

Here’s to longer and longer telomeres!

Doc

New Stem Cell Activating Anti-aging Serums Offer Hope for Damaged Skin

The following is a press release that got generated from a radio interview I did on RG-Cell.  That product is in stock now and ready to ship.  Like I said when we initially released it, there is nothing like it out there!

Damaged and aging skin can now be repaired and rejuvenated, due to new advances in stem cell and telomerase technology. A new topical agent restores skin to a youthful appearance, without a visit to a plastic surgeon or dermatologist.

Many new advances in stem cell and telomerase technology open the possibility to de-age a person’s skin and body, without pain and down time.

Up until now, patients had to see a plastic surgeon or dermatologist to rejuvenate their skin. Recent developments and research in topical agents have made it less likely for one to need Botox, laser or fillers to restore their skin to a more youthful appearance, or get rid of blemishes.

Dr. Dave Woynarowski MD, an anti-aging specialist, states that new combinations of topical serums applied to the skin have yielded some remarkable results, without having painful injections or surgery.

Dr. Dave gave remarks, “I was extremely skeptical about the possibility of repairing damaged skin with a topical ‘on the skin’ agent. After all, the cosmetics industry has been hawking this stuff for decades, to the tune of several billion dollars. None of it seemed to work very well. But, recently there is research to back up specific agents that, when used in combination, can do some pretty amazing age reversal, even on damaged skin. I have a lot of friends who are plastic surgeons or anti-aging dermatologists, so I decided to let them have the latest serum we devised called RG-Cell and see what they said. Bottom line: The patients love it for home use as well as post-treatment recovery, and it really does work far better than any of us anticipated!”

While pleasantly surprised, he also said there are drawbacks.

This procedure takes longer to see results. It is not as aggressive, painful or expensive as injections, fillers, lasers or surgery, and it cannot be expected to deliver the same results in the same time frame.

“The more wrinkled, sun damaged or blemished your skin is, the longer it takes using topical serums to reduce the damage you’ve accumulated. But, there is no down time either because you don’t burn, puff or cut the skin. It’s also very easy to use, so you don’t have to depend on a skin care professional to administer it. Anyone can use it!”

Of course, Dr. Dave encourages visiting a skin care professional first.

“Your plastic surgeon, dermatologist or a good cosmetologist may actually already have RG-Cell, although it is very new and hard to get. Odds are the cutting edge ones will know about it and already carry it.”

How does it work?

Dr. Dave says the ingredients were coupled together to create powerful potential stem cell messengers that activate and support stem cell growth and differentiation. Stem cells are the “repair parts” for all tissues in the body and the skin has a larger volume of stem cells than any other organ system in the body. This makes the skin perfect for this kind of therapy.

“The big ones for stem cells include blue green algae extracts, caviar extract, phyto placenta (not to be confused with bio placenta) and EGF-1 (derived from recombinant DNA sources).”

RG-Cell also contains hydration agents, anti-bacterials and metabolic support agents as well.

One of the biggest advances is the use of a patented nano-particulate lipid bi-layer delivery system that allows the products to be delivered deep into the skin where the stem cells live.

“Lots of things have neat ingredients that don’t get where they need to be to do the job! It literally only takes 4 or 5 small drops once or twice daily to cover the face and neck and it is gone in 30 to 60 seconds, working its way down to the deepest layers in the skin. Thus you can put make up over it in almost no time at all without interfering with the activity of the serum,” says Woynarowski.

Will it work for everyone?

“Nothing works for everyone, including surgery! But we have seen far more dramatic results in a few months than we expected and are happy we have something the professional and the average person out there can use with ease and no pain.”

I know I talk a lot about biochemistry and cellular biology, but what fun is all that if you don’t look good!

Doc

Yet another study connects human lifespan with telomere length

Scientists are by nature skeptics.  Usually it takes more than one positive result and one positive study to convince them.  There is no set number of studies you need to do to sway scientific opinion and quiet naysayers. More often than not, it depends as much on opinion and bias of the so-called scientific community.  This has been proven over and over again with things as diverse as the “earth is flat” to telomeres are merely “markers of aging”.

Well recently another big study showed a direct correlation between telomere length and survival.  It was adjusted for age, disease and other lifestyle factors, yet the correlation still held.

I have often referred to my two favorite tests, Omega 6/3 ratios and specifically short telomere testing as offered by ADL.com as the “BS detectors”. What I mean is there is no hiding from these two tests.  If you think you have a healthy diet, then you should have a good level of omega 3 fats in your blood and tissues and your telomere lengths, again, specifically your percentage of short telomeres, should be better than your actual age.

This is how we predict “biologic age”- how old your body really is, independent of the number of birthdays you’ve had.

I encourage you to look at these tests because, if you are not actually living as healthy as you think, you still have time to do it. It’s easy to fix a low omega 3 level, just take more fish oil.

It’s also easy to help your telomere length but so far there is really only one choice for that as well.  TA-65 remains the only telomerase activator with human data, human cell data, and mouse data. More is on the way, specifically human studies.

While it may take another 100 or even 1,000 studies linking telomere length and telomerase activation to longer and healthier lives, there is enough data right now if you are willing to look carefully. And it may take years for another 100 or 1,000 studies to actually be completed.

While you are waiting, Father Time is eating at your vitality.

I chose not to wait to do something proactive.

Doc

Reference:  http://www.eurekalert.org/pub_releases/2013-03/imc-isf030813.php

Aging fat as a cause for diabetes – the role of short telomeres

Over the past couple of days, I have dug pretty deep into the metabolic associations between obesity, diabetes, and short telomeres. The end result is of course, accelerated aging.

But, more and more I have to tell you, I think aging is the real cause, or at least a major contributing factor to many of the diseases we associate with aging.  In other words, I think we have it ‘bass acwards’.  Fix aging and you’ll probably get rid of heart disease, Alzheimer’s, diabetes, arthritis and cancer, to name a few.

Now understand, we can accelerate the process greatly by eating poorly, sleeping poorly, exercising poorly, or not at all and stressing out more frequently.

From my clinical experience, there is a certain inevitability to many of these diseases and even people who seem to age well eventually get nailed by one or more of them when they run out of telomeres!

So, today I want to share with you a bit about diabetes and how aging fat may cause, or at the very least, contribute to it.

If you look at my most recent blogs, I talk about a hormone-like chemical made by fat cells called adiponectin.  The actions of adiponectin limit appetite, improve sugar control and insulin secretion and are generally anti-inflammatory and anti-obesity.

When fat cells get old, they have the same choices that other cells have. Either kick back in the rocking chair and wait for the grim reaper (senescence), or blow up from the inside out (apoptosis).

It’s pretty easy to imagine an exploding cell being the cause of inflammation, but it’s less clear about the rocking chair senescent ones.  Well, if you’ve read my stuff before, then you are aware of something called senstatic activation or more recently SAPs – the senescent activated phenotype.

Bottom line is, those cells sitting in the rocking chair are fairly oozing pus in terms of inflammatory chemicals.  In the process, they not only become non functional, but they support aging as an inflammatory process all by itself.  The only place I know where you may have heard this before is right here in my blog or my newsletters.  Mark my words, you’ll hear much more about it.

As a consequence of aging, fat cells make less adiponectin and take up less sugar – all of which can lead to or worsen age-related diabetes.

The consequence of all of this is shortened telomeres and a vicious cycle of more inflammation, less adiponectin and more destabilization of blood sugar.

Now here is the kicker.  Depending on the following — genetics, epigenetics and lifestyle — the same processes happen in every other cell and every other disease we associate with aging, including Alzheimer’s, cancer and heart disease, all of which are inflammatory.

Short and sweet: Do everything you can to keep your telomeres longer. I won’t belabor those steps here; you’ve heard them all before if you’ve read our book The Immortality Edge or read any of my blogs in the past three years.

Hint: fish oil and TA-65!

Doc

When therapy is mistaken for normal

In the last blog I delved into some associations between the biologic time clocks we call Telomeres, sugar control and obesity.  The net summary of that blog is that the body has only so many responses to insults like high blood sugar and obesity, and those responses can wind up looking pretty much the same metabolically, even though a fat non-diabetic physically looks much different than a lean, poorly controlled diabetic.  The end result is premature aging and shorter telomeres.

Perhaps the saddest end points of all are manifested in the huge proportion of obese children and adolescents. There is no way you can look at this and not see the role of sugar addiction, carb addiction and sedentary behavior.  Scientists, particularly epidemiologists, will debate all of this ’til the cows come home, and all the while kids are getting fatter. And for the most part dumber too!

I will explain the tie in between those two things in a minute but let me get back to obesity, poor sugar control and its attendant problem, insulin resistance.

Simply put, insulin resistance happens when the body is making more insulin but the cells are not responding to the insulin signal.  This is seen early in the development of Type 2 diabetes. Recall this used to be called “adult onset diabetes” but we had to change the name because now a ton of our kids have it as a result of toxic sugary foods we feed them.

Loads of calories, loads of refined carbs, loads of sugar, loads of insulin, scant nutrition!

The end result of this is 50% of our obese children are already insulin resistant before they hit their 18^th birthday.

This has gotten so bad that some genius (and this time I really mean they are geniuses!) decided to do a study looking at 100 fat kids on fish oil and 100 fat kids on the drug metformin and see what happened to their insulin resistance. In case you don’t know about metformin, it’s been around since the 30’s but has just recently come into favor again in the past decade. Since it’s a drug, it does have side effects including low blood sugar and renal failure, especially when combined with radiologic dye.  Fish oil has none of those side effects and attempts to pin excess bleeding, etc. on it having failed to produce any statistically significant results even when used around open heart surgery, brain injury and in conjunction with prescription blood thinners like clopidigrel. All the fish oil does is make them more effective!

Now you may have also noticed that our kids seem to be put on prescription drugs more and more — Ritalin, Prozac, statins, now anti-diabetic drugs to name a few.  All of this is to modify their behavior, eating or otherwise. It’s a sad testimonial to two things: we do not control our children (as a matter of fact, there is an ever-growing contingent that thinks we shouldn’t “interfere with their experiences”) and we are fine with throwing drugs at them instead of dealing with the real issues that cause these behaviors.

OK, enough social ranting; now let’s look at the study results. As a matter of fact, I am simply going to quote them and then explain them.

“Concerning the IR profile at the end of intervention, ω-3 significantly decreased the concentrations of glucose and insulin while reducing HOMA-IR values; meanwhile, Met negligibly affected insulin levels. Regarding lipids, Met increased high density lipoprotein cholesterol (HDL-C) and decreased low density lipoprotein cholesterol (LDL-C), but triglycerides were not affected; in contrast, triglycerides were decreased significantly by ω-3. The effects on BMI were marginal under Met but were significant with ω-3.”

Ok, what does this mean?  Well the “IR profile” is short for insulin resistance profile and this measured the kids’ insulin resistance.  You see, this got better along with the actual glucose levels and insulin levels. Both metformin and fish oil had favorable effects on various lipid components and the fish oil also decreased the BMI (weight).

Metformin did not improve insulin levels but did improve blood sugar — HMMMM! This is a biggie because, although lower blood sugar is important, the end goal was to improve the insulin resistance. Metformin did not do that in this study. It also did not improve the kids’ weight, whereas fish oil did.

Ok, let’s look at doses.  No attempt was made to define the Omega 6/3 ratios in these kids and they were given a low dose of fish oil (1.8 grams a day).  The dose of metformin was in line with the age of this population.

I would have loved to see the results of this study if the Omega 6/3 ratios had been checked and corrected with the proper amounts of fish oil!  I think they would have been even more impressive.

Let me tell you another thing.  Metformin has become the darling of the anti-aging community because of a study on diabetics in the U.K. where it showed a 30% reduction of cancer in diabetics – not non-diabetics.  As a result, there is a movement among anti-aging types to use it ‘prophylactically’ even though there is not a large body of data in normal non-diabetics.

Fish oil anyone?  I would love to see the same study done head-to-head with Omega 3 and metformin, using appropriate levels of Omega 3 to restore a good ratio.

So what does this all mean to you personally?  Well here’s the thing. We doctors love to give you drugs.  We hate to give you supplements because supplements are “fringe pseudo-scientific quack medicine”- until Big Pharma releases them in prescription form (there are now three prescription Omega 3’s).

Your kids’ doctors are the same.  “There is a drug for that, ya know!”

You might want to suggest a trial of fish oil for your kids and yourself.  Of course I want you to work with your doctor and keep them informed because at least a few of them will do more research and become your ally.

Omega 3 increases also improve cancer rates, arrhythmia rates, heart disease, and believe it or not, things like anti-social and adversarial behavior!

Why?

Because they are supposed to be there in much higher amounts than we get in our diets. That is not therapy! That is returning to normal no matter what the doctors and drug companies try to tell you about prescriptions.

Normal is normal and until we return to normal we will simply be practicing insanity and propagating a string of dietary diseases and premature aging and loss of health.

There are several studies that suggest Omega 3’s improve (they do not lengthen but they preserve) telomere length.  No one is concerned about telomere length in children with obesity and insulin resistance. Perhaps they should be!

TA-65, the only proven (in humans) telomerase activator, is generally not used in children to avoid any potential medical-legal issues.  Same thing with the Telomere Edge Packs, which would otherwise be a great support agent.

But while we wait for our kids to get sicker, fatter and dumber (yes, the Omega 3 situation relates very well to childhood behavior and possibly to IQ!) we as adults can at least undo some of the damage of our diet and environment without drugs!

Disclosure: I make an ultra-clean, ultra-pure, top shelf fish oil that is the kind of thing that you want in your body.

I have for the past 10 years and I have taken what you might consider huge amounts for that time period and will continue to do so for the rest of my statistically longer life than my genetics would account for! Of course I also take TA-65 and have for 4 years now.

Doc

Reference article: Pediatr Diabetes. 2013 Feb 25. doi: 10.1111/pedi.12024. [Epub ahead of print]

Omega-3 polyunsaturated fatty acids reduce insulin resistance and triglycerides in obese children and adolescents.

Juárez-López C, Klünder-Klünder M, Madrigal-Azcárate A, Flores-Huerta S.

Telomere Length and Metabolic Obesity in Skinny People

I read an interesting article recently. Without going into all the gory scientific details, the gist of the article was as follows: even lean diabetics may have the same metabolic profile and telomere length shortening as non-diabetic obese people, if those lean diabetics have poor sugar control.

What is the big deal? Well, it means that, metabolically speaking, your telomeres really don’t know and certainly don’t care if you are fat with normal sugar levels, or skinny with bad sugar levels.

The central problem is a signaling molecule that comes from fat (yes, fat is very active!) called adiponectin.

In order to make sense of the opening statements, let’s take a brief simple look at this fat made hormone known as adiponectin.

Adiponectin is secreted in very high concentrations relative to other hormones, probably because it is so important to metabolic regulation.  It helps regulate appetite, sugar levels and fat levels in the bloodstream.  When it is present in high levels, blood sugar is reduced, appetite is reduced and fat synthesis is reduced.

All good things.

The problem arises when you get fat.  Then, adiponectin levels go down. This is part of what I refer to as the vicious cycle of obesity. Simply put, you getting fat supports you getting fatter and makes weight loss harder. If you’ve ever been fat or know someone who has been for a while, you know the struggles involved.

Here’s a tip: Being fat is inflammatory, and anti-inflammatory supplements can actually increase adiponectin (good!). This includes our old friend fish oil!

If you are not on fish oil, you should be.

Losing weight and reducing your blood sugar, even if you are not diabetic can also help.

Blood sugar control is another big one!  Poor blood sugar control with large excursions into high blood sugar levels can reduce adiponectin levels (bad).

High triglycerides (blood fats) can also lower adiponectin levels.  Remember, fish oil is good for that too! As a matter of fact, the only current FDA approved use for all the fish oil prescription “drugs” out there is to lower triglycerides.

OK, let’s look at this soon to be household word “adiponectin” and telomere shortening.  There is a linear relationship between adiponectin levels and telomere length.  Higher adiponectin levels equal longer telomeres, all other things being equal. Lower levels, as in obesity and poorly controlled diabetes, metabolic syndrome and most likely, low tissue Omega 3 levels, leads to more rapid shortening of telomeres, all other things being equal.

Now rest assured, Big Pharma is hard at work trying to create an “adiponectin-like” drug, which is bound to have horrendous side effects, the way they all do when you mess with Mother Nature.

Fortunately you can control your adiponectin and your telomere length with the following:

1)      Healthy telomeres*

2)      Healthy body weight

3)      Healthy blood sugar control.

In other words, all the things you already knew!

If you need added incentive let me add this:

Being overweight increases the risk of several cancers including breast, pancreas, and colon.

Being overweight shortens your telomeres and your health and lifespan.

Once you lose telomere length from obesity, studies suggest you do not “get it back”, even by weight loss, unless you actively pursue telomerase activation – see TA-65 below.

You do not need to wait until Big Pharma releases their next round of abominations with all the attendant side effects and problems that are bound to happen, when you isolate one receptor and slam it with a drug that is beyond anything the human body was designed to handle.

If you need help, here are a few suggestions:

1)      For weight loss, Ultra Strength Fat Furnace (I cannot tell you it will control blood sugars in disease states, but I will tell you I put some “healthy sugar support” compounds in there!).

2)      For telomere support/telomerase activation, TA-65, The Telomere Edge Packs or better yet, both!

3)      The world’s best cleanest fish oil.

If you can handle things with diet, exercise and lifestyle modifications and you can KEEP doing that day in and day out every day, you won’t need that help and more power to you.

For the rest of us humans, it doesn’t matter how you get there, just get there!

Dr Dave

Chasing the wrong rabbit – why cholesterol levels are just a distraction

There is a 30 billion dollar industry supporting the use of statins for both primary prevention and secondary prevention (after the fact) of heart attacks.  Similarly, hundreds of millions in studies have been spent to “justify the use of statins”.  The JUPITER study is the most recent.  I have already commented on my expectation that Big Pharma will try to position statins as “anti-aging” drugs as soon as enough people are saying the words “anti-aging” to make it OK for conservative medical doctors to look at those words without screaming “fraud and quack”.  To jog your memory, recall my comments on the “Is it Low T” scenario. I still laugh at all the abuse I took in the first 8 years of this century until Big Pharma came out with an acceptable drug for “Low T”.

OK, back to cholesterol and the big 30 billion dollar myth.

Statin drugs lower LDL and this is where, purported anti-aging effects notwithstanding, the major focus of the scientific literature has been.

What an absolute waste!

If you look at the Eskimo population that eats a traditional diet, and the traditional Japanese diet as well, you find loads of people who have high cholesterol.  You will also find more than you’d expect with high blood pressure and, especially in the Eskimos, significant obesity.  But you find almost no heart disease.

No, I am not tricking you by misrepresenting high HDL (good cholesterol) as part of this number. Many of these people do have higher than average good cholesterol but they also have LDL bad cholesterols that would prompt any self-respecting family doc, internist or cardiologist to whip out the ubiquitous prescription pad and start writing for statins and more statins.

OK, so it must be genetics or epigenetics, right? Somewhere, buried in the Eskimo and Japanese genome, there is a magic allele (a variant of the typical gene) that allows these people to stave off heart attacks in spite of too much bad cholesterol, right!?

Wrong!

The whole thing is very simply the effect of their diet because when you take these populations and stick them on our food pyramid or “traditional Western Diet” they develop heart disease and all the other things we get, at exactly the same rates, if not more.

Bottom line: the risk of heart disease in any population is directly related to the Omega6/3 levels.  The higher the tissue levels of Omega 3 (and yes, the blood levels as well), the lower the risk of heart disease.

I tell people to shoot for 1 to 1 Omega 6 to 3, but most of these populations are closer to .85. In other words, they are Omega 3 dominant.  And no, they don’t bleed to death (unless you shoot them), they don’t smell like fish, and the LDL particles that are supposedly causing harm in this situation either go away after a few months on a highly dominant Omega 3 diet or, as in the case of the above populations, they don’t matter.

LDL may wander into an inflammatory lesion and get oxidized but the toxic effects are caused by high Omega 6 levels unbalanced (e.g. in the presence of low Omega 3 levels) in the first place.

The real culprit is free fatty acid release from the liver, which must take place in order for cholesterol to be released as well. Free fatty acid release is caused when the liver gets too many calories in a single bolus to handle them, so it sends them out into the blood where they, along with the Omega 6’s, do the damage.

The cure for free fatty acid release is:  Don’t eat so damn much at one sitting!

So heart disease could be reduced by several hundred thousand people a year by combining the following:

1)         Reduced Omega 6 intake

2)         Increased Omega 3 intake

3)         Smaller meals and, if needed, small snacks in between

You can do most of this with diet alone but the majority of people, myself included, like to eat with other people socially and are more “omnivorous” than we might need to be. Secondly, I don’t really like fish all that much and I do not want all the mercury and other toxins that are in many different fish species, even though the FDA says a little mercury won’t hurt.

There are absolutely no long term studies on “a little mercury consumption”.  My way of thinking is a little over a long period of time can be very deadly, especially since mercurial dementia is not a typical part of the differential diagnosis of Alzheimer’s.  Also I do not want to count on today’s breed of ADD doctors to remember to check for mercury toxicity in a demented 80-year-old?! NO thanks! I will just avoid mercury.

I can’t count on them to chase the right rabbit!

This is why I have my fish oil purified to parts per trillion.

Doc

Telomeres and your heart

Warning: this blog is not just regurgitation or rewording of a press release from somewhere else. It contains original content and original commentary.

Since February is National Heart Health Month, I thought I would update you on some recent advances in how telomere length interacts with the health of your heart.

Telomeres and the heart is a touchy subject for some.  There are still many doctors out there who just skim headlines and don’t read articles. When I am speaking to doctors, I still get asked this question, usually in a hostile tone: “Doctor (there is a certain way they say it that usually indicates they are cardiologists and I am just a lowly internist!), we know that the heart is postmitotic. How can telomere shortening account for dysfunction in a tissue that is not dividing and therefore not losing telomere length?”

Now, since you are probably not a cardiologist, let me tell you what that little paragraph means.

Certain tissues in the body do not divide and have extremely limited capacity to divide once they are fully grown. I say fully grown instead of “reach adulthood” because when you say adulthood it implies you are an adult and some tissues stop “growing” long before that.  And some continue to “grow” with their cells dividing into your twenties.  No matter how you define the above, the word postmitotic clearly means ‘stop dividing’.  This means that the tissue (heart and brain are the two best examples) cannot repair damage by cellular replication the way say skin and blood cells can.  Skin turns over every 72 hours and blood cells, depending on whether they are white or red, can turn over in hours or a few months.

The ability to divide gives the tissue a large repair capacity since it can make new cells to replace old damaged ones.  The postmitotic state of the heart and brain means they cannot repair the damage of say a heart attack or a stroke, and you are likely stuck with something permanent and bad if those tissues are damaged.

This is a huge oversimplification but the ability to divide and repair relies primarily on telomerase expression and a stem cell reservoir.  It turns out that heart and brain, like most other organs in the body, have them both but in smaller numbers, amounts and with an increased suppression of telomerase.  This means that unlocking those things — telomerase and stem cells — could potentially regenerate even these “non-repairable tissues”.

Here is where my cardiology colleagues usually blow it.  They actually forget what they are treating.

I ask, “What are you treating in a heart attack?”  The answer is usually something like, “The heart muscle, you idiot!”

Wrong! Other than the few cardiologists who actually use CO Q10 in their patients, there is not one drug for long term treatment of heart muscle.  Luckily, the heart muscle is not the problem. The blood supply to it is, so you are actually treating the blood supply to the heart muscle, the coronary arteries. And no one debates that blood vessel health function and aging is very much telomere dependent. So age the blood supply to the heart and the heart ages, gets damaged and dies.

Case closed?  Well sort of!

That is only half of the story. You see, God, the universe or Mother Nature if you prefer, gave the human cardiomyocyte (heart muscle cell that does the pumping) longer than average telomeres, at least in those cases where we’ve been able to look at them.  This means that the heart might be more resistant to telomere loss than other tissues. Why would that be the case?

Well, oxygen, the essential element in air that keeps us alive, is a dangerous friend. Why?  Because it can oxidize biologically active molecules by forming free radicals.  The heart is the very first tissue to see that most highly oxygenated blood – so having longer telomeres would be a good thing, giving the heart a little extra mileage in terms of longevity.

Unfortunately we humans have figured out many ways to shorten those telomeres faster than normal.

Here are the usual suspects: a diet rich in inflammatory Omega 6 fats and low in Omega 3 fats, lack of sleep, stress, lack of or too much exercise, a nutritionally poor diet lacking vitamins minerals and antioxidants.  All of this helps speed up the loss of our telomere biologic time clocks in all cells, not just the heart.

But there is still one more piece of the puzzle and this is the really cool part.  Over the past decade or so a huge project looking at the human genome, called ENCODE, has been going on. This is part of the reason why epigenetics has become a hot topic.  But just as epigenetics was hitting its stride as the du jour household word, information came out about a bunch of other “factors” that influence how our genes are read.   As a reminder, we age not because of changes in our genes, but how our genes are read, so pay attention here.

One of several “new” (new here meaning not commonly known by the public!) messengers have been discovered. One of them is call miRNA short for micro RNA. If you remember high school biology, RNA is the stuff that you make from “reading DNA, the genetic blue print”. That RNA usually goes along and gloms on to some protein factory somewhere and some enzyme or other messenger protein is made.

Not so with miRNAs. Their function is strictly to turn something on and off. As far as we know, they don’t ‘make’ anything.

OK, now back to the heart. An miRNA was recently discovered called miR-34a.  MiR-34a is associated with two big things: an aging heart, which makes more of it and MI’s, more commonly known as heart attacks. Once again, this is a gene off/on signal that rises with aging and changes which genes are read and how.

If you block the production of this particular miRNA or its target called PNUTS, you reduce heart cell death rate following heart attack and you reduce scarring. You also reduce the age-related decline in heart function.* How?  By reducing the end point of all this, which is telomere shortening in the heart.  So all this great new stuff points once again to our old friend the telomere as the central actor in determining who lives and who dies in the heart and otherwise!

Another why: because the telomere governs the damage response of the cell and whether it lives, senesces (slow death) or explodes from the inside out (apoptosis). And heart telomeres get shorter just like any other telomere! And because they normally express absolutely no telomerase, they are even more susceptible to telomere loss even if they start out with longer telomeres than other tissues.**

That is enough science for today but let me sum it up even more simply for you.

Heart disease is the number one cause of death in this country.

Telomeres rule!

Take care of your telomeres.

Don’t forget your fish oil and TA-65.

Happy Healthy Heart Month!

Doc

* This is still at the laboratory level and has not been tested in living people!

**Well established norms for telomere length in various tissue types have not yet been explored fully.

Reference Nature 2013  Feb 20

MicroRNA-34a regulates cardiac aging and function.  Boon, et al.

Colds and Chromosomes – how telomere length affects cold symptoms

Have you ever heard someone tell you, “I am sick all winter”, or “I am always sick”?

Barring allergies, this could actually be a symptom of short telomeres and a weak immune system.  Can one exist without the other? Well, the immune system is a complex interaction between all kinds of cells that “present” pathogens and others that fight them off – but with aging, it’s pretty clear the T cell compartment takes a pounding.  That means that premature aging will do the same thing.

And what measureable event happens in senile T cells?  Their telomeres shorten!

Conversely, if you treat with a Telomerase Activator like TA-65, the immune system “de ages” and the T cell compartment gets stronger with longer telomeres.

Now this has a lot of implications, especially if you believe as I do that the immune system maybe the central coordinator of the aging process (in response to increasing percentages of short telomeres).

On a more basic level, a recent study in the Journal of the American Medical Association found that people with shorter telomeres got colds more frequently and had worse symptoms than those with longer telomeres.

This of course mirrors our experience with TA-65.  Fewer colds are often one of the most common things people notice and report.

One of the most interesting things about this study is it was done on relatively young people (ages 18 to 55). This means that shorter telomeres have clinical implications long before we reach old age, something that scientists are just beginning to understand now. Globally there was a 25% decrease in the infection rate based on telomere length.

Now if you remember pneumonia is the “Old man’s friend” and that infection and cancer are the big killers of the older old (85 to 100) you can also see the implications for life extension!

In addition to considering TA-65, I should remind you I also make something called Immune Booster. The active ingredient (elderberry extract) has been shown to interfere with viral binding to cells, thus helping to prevent spread of viral infection in the first place.

No matter how you look at it, the immune system has major implications for your health, work, and convenience.  And maybe if you are older or have a weak immune system it goes far beyond that.

It may affect your longevity.

Catching fewer colds is no joke!

Stay young strong and healthy!

Doc

Reference: Association Between Telomere Length and Experimentally Induced Upper Respiratory Viral Infection in Healthy Adults

Sheldon Cohen, PhD, Denise Janicki-Deverts, PhD, Ronald B. Turner, MD, Margaretha L. Casselbrant, PhD, MD, Ha-Sheng Li-Korotky, PhD, MD, Elissa S. Epel, PhD, William J. Doyle, PhD

JAMA. 2013;309(7):699-705. doi:10.1001/jama.2013.613

Biosci Biotechnol Biochem. 2012;76(9):1633-8. Epub 2012 Sep 7.

Anti-influenza virus effects of elderberry juice and its fractions.

Kinoshita E, Hayashi K, Katayama H, Hayashi T, Obata A.

Telomeres and Drugs and Big Pharma

Heart disease has one of the longest standing associations with short telomeres.

Recently a similar association was established for strokes (thrombotic ((clot) and hemorrhagic (bleeding)).

The limitations of these studies in terms of direct correlation are that they are not using modern technology to determine the shortest telomere lengths or percentage.  They are still using out-moded technology known as PCR. Interestingly, one of the main champions of this technology is a lab here in the U.S.  It’s up for sale now if you have a few spare millions!

Then again, if you have few spare millions, you’d be way better off investing in Life Length, which uses patented proprietary technology to measure not only average telomere length but the percentage of critically short telomeres – the ones that actually cause aging and disease!

As illness after illness in the category we call disease of aging (heart disease, cancer, Alzheimer’s, arthritis, etc) is linked closer and closer to telomere shortening it should also come as no surprise that Big Pharma is circling the wagon, waiting for someone small to take the risk, develop the product and then swoop in and capitalize on someone’s sweat, equity and intellectual property.

But don’t trademarks and patents protect you?  Only if you have the money to defend them.  Ask me how I know!

If you’ve even been involved in a lawsuit, you know that being right or guilty often comes down to how much you can pay the legal team. With a budget in the double-digit billions, would you want to take on Big Pharma?

So what are they up to in the telomere field?

Well, the first thing will be using technology like short telomere testing to define what drugs are “good for you”.  The better part of this role is that one can also look at certain groups of people, classify their telomeres and determine whether or not certain drugs are likely to be beneficial for them.

The preliminary work has already been done for statin drugs and it turns out that among people with heart disease it looks like those with the shortest telomeres benefit most from statin drugs – although statins do not lengthen telomeres.

Also, predictably, the effects of statins, which on the telomeres are the same as antioxidants and fish oil, are now beginning to be talked about as “anti-aging” drugs in traditional allopathic (doctors with MD and DO behind their names).

I can’t help but laugh at this because it reminds me of what I call the “Testosterone scenario”.

Fifteen years ago, if you helped treat your patients with congestive heart failure, diabetes or osteoporosis, or simply age-related declines in testosterone, you would have been called a quack or out of your mind.

Again, ask me how I know!

Now you see TV commercials asking, “Is it low T?!”  And while you are listening to those commercials, listen to the relatively short and relatively benign list of side effects compared to the other drugs Big Pharma is hawking on TV! So quackery becomes safe and effective therapy.

Likewise, don’t be surprised if you soon see the words “anti-aging” become part of the regular doctor vocabulary and statins touted as anti-aging drugs. Once Big Pharma says it’s OK, it’s OK.

Never before and if you are 15 years ahead of Big Pharma and now you are “correct” no one comes up to you and says,  “Hey, I take those quack remarks back!”

Now for the real question – what will they leave out?

1)      A thundering herd of people will not benefit from statins. Why do you think there have been hundreds of millions of dollars spent on proving that statins work in trials like JUPITER ((Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial). We are still trying to justify their use and cost even though heart disease is an inflammatory illness. Even JUPITER states the many effects of statins are NOT related to cholesterol lowering.  Talk about the world’s most expensive antioxidant!

2)      Not all statins are the same and only one has been tested in this way.

3)      By keeping one’s telomeres long and adding in the right dose of Fish Oil, you might delay heart disease and other illnesses that are associated with aging.

4)      What about drugs that shorten telomeres? Do you think you will find out about that? Only if that drug is already on the chopping block and there is a replacement ready and waiting that can make up the profit margin.

And while everyone is hunting for the big drug pay day, there is a little-known nutraceutical that has human safety and efficacy trials and has been shown to turn on telomerase and lengthen critically short telomeres.

It is called TA-65.

I somehow doubt Big Pharma will tell you about that either until they own it.

Doc

Telomerase magic

If you study the biologic time clocks in the cell, known as telomeres, and you study the enzyme that lengthens them, telomerase, you are truly learning about magic.

Here are a couple of amazing things I have learned:

1)      Telomeres are intimately involved with just about every longevity and health pathway known to science.

2)      Preserving telomere length and healthy function seems to reverse a lot of, in some cases, all of the cellular defects that happen as a result of all those other pathways. Here is an example: We know that oxidation (free radicals) damage cellular mechanisms and damage telomeres. Longer telomeres actually may be more susceptible to free radical damage because they have more DNA available for oxidation. Yet, when their length is preserved, the sum total effect of free radical oxidative damage in the cell is reduced, or even reversed, indicating their central and governing role in the pathways that are activated by free radical damage. I can’t say free radical damage doesn’t matter, it does. But, it matters a lot less when you have longer healthier telomeres!

3)       Adding telomere length and function, particularly by limiting the number of critically short telomeres, or adding to their length, reverses the aging process in mammals and slows or stops the aging process (DePinho and Blasco separate studies). Improvements are seen in the same cellular populations as those seen when TA-65 is used to treat people and lab animals. Those areas include boosting the immune system, the brain, the skin, the handling of sugar, the handling of fats, and the amount of inflammation in the body. Some other things that are difficult to measure in animals show up in people, including increased sex drive and increased focus and energy.

4)      The gene for the enzyme telomerase is found in every nucleated human cell type, which is basically most cells in the body, with the exception of red blood, which lack a nucleus and most organelles to accommodate maximum space for hemoglobin. Everything else with a nucleus has telomerase. But, in most cells with again a very few exceptions, telomerase is repressed or turned off. Since we know telomerase is needed for cellular immortality and so far no other way has been found to immortalize cells, the gene for immortality is inside every cell. But it’s turned off.

5)      Some cells, like those of the immune system and stem cells have more telomerase expression, but as they become more “mature” types, the amount of telomerase, which is already small, declines even more.

6)      Germ cells, specifically sperm progenitors, may be the only cells in the body with enough telomerase to outpace the aging process.

7)      When telomerase is turned on in most cell types, it “fixes” the critically short telomeres first. This is also seen when telomerase is induced by TA-65, suggesting the way TA-65 works is totally “natural” and in harmony with the body’s established processes.

8)      So far the only way to stop cells from aging is to turn up the telomerase.

9)      TA-65 is the “only proven in live people” way to do that, so far.

In my last blog, I alluded to this kind of magic being baby steps. But in my view, anything that can help people live longer healthier lives is still magic!

Doc

Is Aging Unstoppable – Baby steps come first!

Arguments continue among the best and brightest scientists concerning the question: Is aging unstoppable.

If you think about it, that question has already been answered in a functional way. There are several mammalian cell lines that have been made “immortal” simply by turning on telomerase and expressing it at a higher level than normal.  Most surprising is the absence of increased cancer in many of these experiments.

If you look closely at the scientific literature, the question of whether telomerase causes cancer has already been answered many times over with a fairly resounding “No, telomerase does not cause cancer!” It has been almost 8 years since a scientific paper has raised that question. Understand this is different than commentary, different than blogging, different than social media and all the other places where people get their “information” these days.

Just like there are still people who are dedicated to the notion that telomerase might cause cancer, there are also people dedicated to the “Anti-Anti-Aging” agenda. This group ranges from the “We should all die to make room for the youth” to the “Well we might live forever but telomerase is NOT the answer” crowd.

To the first group, I say, “Put your name on a list and we’ll make sure you don’t get anything that would prolong your health span and life span – then you can die happy in the fact that you’ve made room for someone else”.

To the second group, I say, “Well then, show me what the answer is and please show me anything else that has immortalized cell lines or added life and health span to mammals.”

The recent issues surrounding the failure of calorie restriction to deliver the former should be noted. Increasing health span (how long you are healthy) with increasing life span is the bailiwick of telomerase expression alone.

And if you think about it, if you could be healthier while living longer, why not?

Now it’s time for a couple of concepts that have been really hard for me to get across.

1)      Aging has been partially reversed in living mammals (mice) by increasing telomerase expression. In at least two separate studies (Ron DePinho and Maria Blasco) the reversals were dramatic. Additionally, Dr Blasco later showed that mice are indeed a valid model for human aging, shutting down the argument that “mice don’t age by telomere loss”.  Yes, they do and I have detailed that study for you in other blogs and plan to discuss it directly with Dr Blasco in the next couple of weeks again.

2)      Telomere loss is the result of two main things: cellular replication and direct damage that can happen pretty much any time.

Cellular replication is unstoppable and a necessary part of being alive. The only way to slow down the loss of telomere segments during replication, which is always there and always chewing away at them, is with a Telomerase Activator such as TA-65.

The rest of the damage is environmental/lifestyle and can be slowed down by proper lifestyle choices including stress relief, exercise, nutrition and so on. But this is only going to slow the process, not reverse it.

Recently I saw yet another blog that said, “Fish oil leads to longer telomeres!”  By now you should know I am a huge champion of fish oil.  I would love nothing better than to see it “lengthen telomeres”. But it does not. It slows down the loss. This is huge and meaningful and wonderful, but it’s not TA-65!

The problem arises because, compared to the people who did not take fish oil, the ones that did have “longer telomeres”.  But no one looked at their telomere length to begin with, only after the fact in the two groups. If they had, they would see that concept #1- telomere loss due to cellular replication caused BOTH groups to have shorter telomeres than when they started, so NO ONE actually had longer telomeres than when they started.  The fish oil group had longer telomeres than the other group at the end of the study when they were measured but still lost telomere length overall due to cellular replication.

There is no easier way to explain it!

OK so what is the bottom line?

1)      Aging can and has been stopped by telomerase activation to lengthen critically short and eventually most telomere lengths.  In this way you can stop the #1 loss – replication.

2)      TA-65 is the only compound with solid human (or actually ANY human) data showing its effects on telomere length and causing health benefits in human beings that correlate with “anti-aging” effects. TA-65 increases telomerase expression.

3)      Live organisms have had their life spans extended past what is known to be the maximum in the wild and in the lab by increased telomerase expression with no increases in cancer.

4)      Health span and health parameters parallel each other from human cell lines to mammals to human beings – with similar systems being improved, including: immune, skin, brain, behavior, inflammation, sugar handling, fat handling.

5)      Fish oil, especially fish oil, has been shown to slow telomere loss in meaningful (clinical) fashion as well as some other antioxidants, but none have shown increased telomere length in humans. Slowing down loss is NOT THE SAME as adding length. But when you look at oxidative environments, antioxidants and Omega 3’s can reverse some of this damage and telomerase seems to take care of the rest.

What steps should you take to lengthen your telomeres or at least slow the loss?

Read our book The Immortality Edge if you are not already clear on what lifestyle modifications matter.

Next, get and take enough fish oil to reverse the omega3 deficit in your body. If you are not sure where you stand, then get our Ideal Omega test and find out.  Yes, you can also reduce your Omega 6 intake to a great extent and this will be included in both of my forthcoming books.

If you can afford TA-65, by all means do so. If not you might be interested in the new and improved Telomere Edge Packs.

If not, then focus on things like Vitamin D and CoQ 10 to boost your antioxidant defenses.

I firmly believe that aging can be stopped in humans. I also believe that it will take baby steps first to get there and yes, we are in the “baby step” age right here, right now. But if you don’t take those baby steps now you may not be able to walk or run when the time comes.

Doc

Curr Aging Sci. 2013 Jan 22. [Epub ahead of print]

Telomere Shortening Is a Sole Mechanism of Aging In Mammals.

Mikhelson VM, Gamaley IA.

Old Dad versus Young Dad – who should father children?!

Ah yes, the more we know, the more we don’t know!

In this country and other Western nations there seems to be an increasing trend for men to father children later in life. Now if you think about it, this is a little bit like the obesity epidemic!  For both things it’s the very first time in human history where large populations of people have strayed from what had been the norm for literally hundreds of thousands of years!

And as you might guess, it has caused some problems and also has some benefits.

Let’s focus on the problems first. When men father children at an older age, there is a higher incidence of neuro-psychiatric disorders like schizophrenia and autism. While far from being a one-to-one correlation and also far from being totally proven – this stuff has gotten a lot of press because of the devastating effects on the offspring.

Again, while far from proven, the logic behind how this happens is as follows.

Sperm, unlike eggs, continue to express telomerase throughout a man’s reproductive life and the telomeres get longer as the man gets older.  This is completely the opposite of almost all the other cells in a man’s body. But this “increased number” of replications allows the DNA copying machinery more chances to mess up. One thing we know for sure is cellular replication – especially the DNA duplication part – is not perfect.  This then should be a source of errors in the germ cell (in this case the sperm cell!) line.

The most recent paper on the topic suggests that this is not so, but does not discount the possibility of other age-related factors in the father, leading to increases in the above disorders as well as some far rarer ones like Marfan’s Syndrome.

OK, now for the part they don’t tell you.  Increasing Paternal age at the time of conception is also independently associated with longer telomeres in the offspring.  This then is associated with more resistance to clogged arteries (atherosclerosis) and yes, a longer lifespan, which can be passed on for several generations since these kids have longer telomeres to begin with.  It might take 4 or 5 generations of their grandkids and so on having their own children at young ages to lose this advantage.

Now it is impossible to weigh the odds and emotional/financial drain of having a sick child versus a long lived healthier child based on paternal age and telomere length alone. But don’t be surprised if in the next few years tests exist to detect and predict those odds for the next generation.

In the meantime, men and women, keep your telomeres as long as possible because you never know when you might need to feel and act young!

Dr Dave

Int J Epidemiol. 2013 Feb 4. [Epub ahead of print]

Leukocyte Telomere Length and the Father’s Age Enigma: Implications for Population Health and for Life Course.

Aviv A, Susser E.

Hum Genet. 2013 Jan 13. [Epub ahead of print]

Increased paternal age and the influence on burden of genomic copy number variation in the general population.

Buizer-Voskamp JE, Blauw HM, Boks MP, van Eijk KR, Veldink JH, Hennekam EA, Vorstman JA, Mulder F, Tiemeier H, Uitterlinden AG, Kiemeney LA, van den Berg LH, Kahn RS, Sabatti C, Ophoff RA.

Stress Kills Right?

Ever since the emergence of the so-called Type A personality some 50 years ago, scientists have struggled to understand the relationship between stress, disease, and aging. We all kinda knew there had to be a relationship, but the data did not always bear it out.

All kinds of statistical machinations were needed to make things fit but eventually the problem was discovered to be lack of information. What we did not know and had a hard time measuring, falls under the realm of “psycho social interactions”.

Simply put, the resources a person has to deal with stress make all the difference in the world, more or less independent of the actual stressor.

Examples of positive stress modifiers include:

• Meditation and other specific stress relievers (bio feedback, etc)
• Economic status
• Education status
• Social Support
• A Past History of chronic stressors

Still, it was very difficult to actually measure much. Questionnaires were subject to the memory and bias of the person filling out the questionnaire. You could measure end points like heart attack, cancer, dementia and so forth, but you really had a hard time fitting all of this into “dying before your time”.

Then along came the telomere, the biologic time clock that governs the actual lifespan of the cell and thus the organism to a large degree. Telomere measurements have advanced greatly in precision and accuracy with the best test being the Life Length HT-Q Fish assay developed by Maria Blasco.

Using precision testing allows us to make direct correlations between stress and biologic age.

Remember your biologic age is how many tick tocks are left on your clock and is often quite different than chronologic age – how many birthdays you’ve had.

Recently a large ethnically diverse study looked at telomere length in people recovering from heart attacks.  The study was adjusted for smoking, weight, age and other factors known to shorten telomeres.

Thus the numbers they generated were directly related to the level of social support a person had while recovering from a heart attack.  Social support in this context includes familial care givers, hired care givers, extended circles of friends, and community involvement (social organizations) either by the person or with the person (community outreach programs).

Now I am going to ask you to guess what they found.

In case you need a little help, here are some previous things that were associated with shorter telomere lengths.

• Being the care giver of a chronically sick child or adult
• Growing up in an orphanage
• High levels of perceived stress

Ok, I hope you figured out that the lower the level of social support, the shorter the telomeres and the higher the likelihood of illness and death.

These factors are something you can modify and you are never too young to start. Keep your friends close, join at least one organization that allows you to socialize, consider volunteering in an outreach program so you can see firsthand what it’s like.

Oh yeah, it doesn’t hurt to be above average in the smarts and income department either.

In a very real way how you live your life and how you fulfill your potential impacts on how well you age!

Now, with the advent of HT-Q FISH telomere testing, you can “see how you are doing” in a very real sense and you have time to make the changes you need to live longer and healthier.

Doc

P.S. For more on Telomere Testing, visit www.adltests.com.

Fish oil and Telomeres – it’s all about length

I want to believe; I really do!  I want to believe that fish oil, specifically MY fish oil, is a telomerase activator!  But there is this little thing called lying that I am not willing to do.

So here is the truth:

I sent my fish oil to Sierra Sciences for telomerase evaluation and it did not turn on telomerase at the typical doses I recommend – 3 to 6 grams a day.

But all was not lost, because of all the supplements I tested (mostly BS stuff claiming to be telomerase activators and of course resveratrol) my fish oil was the only one that came back as “increasing cellular viability”.

What does that mean?  It means that more cells were alive and healthier at the end of the day – sort of a cellular definition of “Healthspan”.

So this reminds me: if people are going to make claims, I really think they should be responsible for testing the statements for truth.  I do it and, in my opinion, it should be the individual responsibility of whoever is selling, to do the same.

But wait, there is more!  There ARE studies that suggest fish oil is indeed a telomerase activator, as well as an inhibitor.

Now if this confuses you, hang in there for just a moment.

There are two important studies that point to fish oil’s actions on the telomere. One involved people with heart disease; the other simply involved sedentary middle-aged people.

Something happened that is far more important than turning on telomerase and maybe even more important than lengthening telomeres.

People in the heart disease group just plain old did better with more fish oil on board – and yes, fish oil was a big part of how they got their levels up, in spite of the ridiculous and unending suggestions that fish somehow contains a magical element. It does, but it is called Omega 3 and it is cleaner and more concentrated in pills.

Also, understand that while avoiding omega 6 fatty acids is really a very good strategy, most people do not do it and wind up relying on supplements. Sorry, gang, it’s just easier and trust me, the gurus in the field are taking supplements, not ingesting mercury from fish!

In the other study, the effects of fish oil on the telomere were directly related to the reduction in inflammatory markers.

I have written a lot about how vulnerable telomeric DNA is to oxidation in a bunch of my recent blogs, so this is not really a surprise.

Now here is the thing: Fish oil may indeed be an indirect telomerase activator by “downstream” signaling molecules, especially if it is used at high enough doses.  No one has really done that study yet, because most people are not taking as much fish oil as I do.

And while the jury is still out on this, there are so many other reasons to take fish oil that it almost doesn’t matter.

Besides, there are two other great things you can take specifically for your telomeres: The Telomere Edge Pack and the world’s only “proven in humans” telomerase activator, TA-65.

In the long run, it is all about length!

Doc

Recommended reading:

Brain Behav Immun. 2013 Feb;28:16-24. doi: 10.1016/j.bbi.2012.09.004. Epub 2012 Sep 23.

Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial.

Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E.

Source

JAMA. Author manuscript; available in PMC 2010 February 10.

Published in final edited form as:

JAMA. 2010 January 20; 303(3): 250.

doi:  10.1001/jama.2009.2008

PMCID: PMC2819264

NIHMSID: NIHMS172565

Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease

Ramin Farzaneh-Far, MD, Jue Lin, PhD, Elissa S. Epel, PhD, William S. Harris, PhD, Elizabeth H. Blackburn, PhD, and Mary A. Whooley, MD

Lipids Health Dis. 2008; 7: 37.

Published online 2008 October 15. doi:  10.1186/1476-511X-7-37

PMCID: PMC2576273

Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules

Undurti N Das 1,2

Food for life – Broccoli and Telomeres

Many herbal and plant-derived compounds show anti-cancer activity.  Sadly, until someone figures out how to make the big drug pay day by changing them just enough to patent them, no one listens.  This is especially true of doctors who forget that 90% of drugs come from “refinement” of natural sources and the other 10% that are computer modeled are usually found in nature soon after.

I have written about Di Indole Methane and Sulforaphane extensively in the past.  Both are present in therapeutic amounts in broccoli and Brassica vegetables. In addition, the Brassica family is one of the few vegetable families that have a balanced Omega6/3 ratio, making them even more attractive.

Now there is a new kid on the block, from Broccoli and the like, called 4-methylthiobutyl isothiocyanate (MTBITC), and like Sulforaphane and Di Indole methane, it has potent anti-cancer activity. It works by damaging the DNA of cancer cells and it also turns down the telomerase in those cells, making them more susceptible to auto suicide and chemo agents.

A couple of things: remember cancer is not a normal cell and that telomerase activation is often the last step in cancer.  Next, remember cancer hijacks telomerase – telomerase does not “cause cancer”.

Finally, remember the telomerase activator, TA-65, has been shown not to accelerate cancer transformation, or increase cancer risk. No other compound sold for human consumption has human data or cancer data either. So if you are swallowing something other than TA-65 that claims to be a telomerase activator, get the company that makes it to show you how they tested for cancer!

You will not get a reply!

Now here is a speculative but worthwhile thing: Eating Brassica vegetables may have an anti-cancer effect as well as a hormone balancing effect.  No one is going to study this again since the “Big Drug Company Pay Day” doesn’t come from food.

It happened to fish oil as there are now three “drugs” that are essentially fish oil on the market. I wonder if the broccoli-derived drugs will be in green capsules.

Doc

Reference article: The MAPK Pathway Signals Telomerase Modulation in Response to Isothiocyanate-Induced DNA Damage of Human Liver Cancer Cells  PLOS One. Evelyn Lamy, Corinna Herz, Sabine Lutz-Bonengel, Anke Hertrampf, Melinda-Rita Márton, Volker Mersch-Sundermann Published: January 31, 2013

Telomere maintenance – We who are about to die Salute You

In my most recent blog, The Monster is Not Born Immortal, I discussed in real time the results of Dr Maria Blasco’s most recent paper using both telomerase over expression and Calorie Restriction.

As usual, I got a bevy of comments, many of which were nasty grams and did not get published for that reason, on the blog.

People do not like to see their belief systems attacked.

The one that has come into question most recently, is based on the statement: “The only robust way to extend mammalian longevity is calorie restriction”!

Based on the recent monkey fiasco and Dr Blasco’s findings that her calorie restricted mice did NOT live longer, I think that phrase needs to be changed to:

“The only way to robustly extend mammalian lifespan is telomerase over expression!”

I honestly think Dr Blasco’s achievements in the past year warrant a Nobel Prize.

1)  She successfully extended mammalian (mouse) lifespan with the AAV 9 virus and did not increase cancer incidence.

2)  She showed how mice actually do age like people based on her assay (Life Length www.ADL.com), following the percentage of short telomeres.

3)  She showed how telomerase over expression is probably the main, if not the only key to true life extension in mammals.

Now, let’s talk briefly about calorie restriction (CR). There are approximately 10,000 people who follow the discipline worldwide, at least to some degree.  When these people die, we should salute them since they have carried on what must be the first true human longevity experiment. That is, assuming they do not believe any of the most recent findings that point away from CR as a valid life extension method.

In the meantime, what about all the darlings of science: mTor, Foxo, sirtuins?  More and more it looks like these are “healthspan pathways” that have the most effect when someone, or more specifically some animal, is sick or stressed.  Remember CR may be its own stress, but ultimately, even though animals who are CR’d do not live longer, they do seem to be healthier up to the point when they die.

Does this work in people?  Preliminary findings suggest that in heart disease, metabolic syndrome, diabetes and other types of similar age-related diseases, CR does indeed improve outcomes.  It also seems to help Alzheimer’s and we wonder… Cancer?

Here is where the problems start to come in.  By the time you have cancer, you might also be protein calorie malnourished and CR might worsen everything. There are studies that do show it increases mortality and morbidity in some animals. And by the way, if you want to look at a free living population of protein calorie malnourished people, try the elderly.

They seem to get sick and die at a higher rate than the rest of us! So we may find that CR ultimately shortens human lifespan in non-obese populations, echoing my title for this blog.

And while I am at it, I may as well talk about resveratrol, another darling that has lost its shimmer.  Recent studies show resveratrol does not even work through the primary sirtuin system and even if it did, that system is not a longevity pathway in people. It’s an energy management pathway.

As I have said before, it’s a decent antioxidant if you want to take it but do not look to it as a longevity drug!

Over the years, I have voiced all these opinions before and taken a lot of abuse because of my stance.

But, I really don’t care because I am not going to do anything that is not well researched and reasonably proven, and I am not going to stake my health and longevity on it either.

What about TA-65; is it a longevity drug?

Again, the abuse flows both from people who do not believe in longevity as a concept and from others who claim to have a telomerase activator of their own.

My stance remains the same:

If you want to age and die prematurely that is your choice, please proceed by all means!

TA-65 is the only telomerase activator currently available that has ANY human data and more is on the way. Since it’s not a drug, we can’t call it a longevity drug.

But, we could call it a longevity compound since it mimics many of the effects of telomerase over expression by virus or genetic manipulation, including immune boosting, bone mass improvements, anti-inflammatory effects, skin aging decrease or reversal and many metabolic turnarounds.

Since this is my passion and my profession, I want to do everything that makes sense to improve my chances, while we hash out what else is super important in this quest for a better life with better health!

We may yet find that CR makes sense for some group of sick people wanting those things, but we know TA-65 already does.

Doc

P.S. We do owe a debt of gratitude to the CR folks since they are actually trying to find an answer and are willing to sacrifice their lives and some considerable enjoyment of same to get that answer.  I sincerely hope the CR society approaches Life Length to do short telomere testing, since it may provide them with an answer that doesn’t require them to die first!

Hard as Nails versus Tough as Nails – more than a name!

I had an interesting discussion with a friend of mine the other day about character, specifically strength of character.

The phrase “Hard as nails” came up over and over again in almost every imaginable context: business, physicality, relationships, dealing with people, friends, family members and so on.

My friend then said to me, “Doc, you must be Hard as Nails to do what you did – taking care of sick, dead and dying people day in and day out.”

I said, “Absolutely not!”  I went into a litany of traumatic and tragic events a mile long stretching over two decades of medical practice.  Some were pathetic, some were full of suffering, some were mind-bogglingly unlucky and some were just plain old soul-wrenchingly sad.  I then mentioned some more personal experiences of the same kind. The incredible emotional trauma, the tears, the loss, everything that goes with grieving and more.

My friend was flummoxed and just shook his head. “How?!” he said not even needing to complete the sentence.

I used the usual and true analogy of “Well, there were some huge triumphs and some wonderful feel good moments!”

But in truth he and I knew that alone was not enough so I added, “Besides, I may not be hard as nails but I am tough as nails!”

I chose to rebound no matter what. I look at life as a challenge to be embraced and self mastery is a huge part of that challenge no matter what realm of life we are talking about.

I also honor myself and those I love by sharing my anti-aging knowledge and discoveries.

As a matter of fact, I do that for you too, so in some way I guess I must love you too! LOL!

But seriously now, try to love yourself enough to treat yourself to the best whenever you can because usually more than you are counting on you, if you know what I mean.

Ponder this, the name of my company, Dr Dave’s Best. It’s more than a name; it’s a philosophy.

“Conquering others requires Force”

“Conquering oneself requires Strength” Lao Tzu

I will take Strength every time.

Stay well, and Stay Strong!

And thanks for being one of Dr Dave’s Best!

Doc

The monster is not born immortal: When telomerase drives cancer

A recent German study has found an association between familial and non familial malignant melanoma and the telomerase gene.  I think we should talk about this because it shows where the seemingly unending association with telomerase and cancer came/comes from.

First concept: Cancer cells are not normal. They are the result not only of loss of growth control but of multiple other aberrations and mutations that change them into monsters. This most likely happens long before they hijack telomerase.

The monster is not born immortal.  The immortalization of any cell line appears to involve OVER EXPRESSION of telomerase. So when the monster that is cancer is born there are many places it can be stopped before it takes over the village. The problem is the village elders (in this case the immune system) are weak, old and disorganized.  Too weak, too old and too disorganized to stop it.

So it grows more powerful with every step (cell division) and eventually obtains the ability to hijack several processes including the ability to invade surrounding tissue (matrix metallo-proteinases), carry away its own anaerobic excrement (angiogenesis), and finally its own immortalization (telomerase).

Second concept: Telomerase is not oncogenic by itself. The enzyme telomerase does not cause cancer and may actually help prevent it (JAMA 2010 article showed association of short telomeres and poor type and prognosis of cancer).

The monster has to be “made” before telomerase gets involved and then it hijacks telomerase for its own purposes.  In the cell lines studied the hijacking of telomerase was the LAST step in the creation of an immortal cancer cell.

The amount of telomerase needed to sustain cancer growth in general is massive.  While I cannot assign an absolute number to it (telomerase expression is measured in arbitrary units and no one has done this comparison study) it could easily be 20 to 100X the amount present in those cell lines that actually express telomerase. This is far beyond the amount provided by TA-65, which is usually the next question I get asked.

When you add TA-65 to pre existing cancers (xerographs) there is no change in the cancer growth rate and as we have seen in mouse studies, no increase in the rate of cancer formation.

The same holds true for some genetic manipulations and also for Maria Blasco’s AAV-9 virus with regards to cancer formation.

Third concept: Telomerase inhibition as a sole or adjunctive agent to fight cancer is likely to fail for the following reasons:

a)      Most cancers are capable of using an alternate (ALT) method of preserving their telomere length. Destroying the telomerase dependent cells (the competition) allows the ALT cells to thrive and multiply. There are at least 2 studies where this has happened. ALT is often associated with cancers that are more deadly and more resistant to treatment.

b)      Inhibiting telomerase may weaken the already weakened immune system in the cancer patient which of course may be further weakened by chemo and radiation. It may also inhibit the growth of healthy tissues.

Forth concept: Mutations in the telomerase gene have been shown to be associated with super longevity.

Fifth concept: Increased Telomerase expression at sub cancer levels has been shown to improve the parameters of health and longevity. So far the only proven ways to have enough telomerase to actually affect telomere health are: TA-65, virosome expression, genetic “boosting” of telomerase.

Sixth concept: So far in humans the only safe way to affect telomere length (critically short telomeres) is TA-65. No ethics committee is going to allow a healthy human to be injected with a virus (ask me how I know!) and genetic boosting of telomerase still carries with it a risk of cancer.

The pharmacologic or more correctly nutraceutical approach (again TA-65) has the he advantage of being on then off and non constitutive (not continuous) and well below the threshold for cancer.

OK back to the German melanoma study before we wrap this up. After the researchers found a familial mutation that is associated with melanoma they looked at non familial cases.

Guess what! They found it was a frequent mutation in melanoma, although not the same mutation.

Honestly, guys, is that really a surprise given that cancer as a process hijacks telomerase?

My only hope is that other cancers will be studied this way. I am sure they will find similar situations there as well where the creation of cancer leads to a mutated form of telomerase.

Sadly the lead researcher in this team went on to talk about how telomerase inhibitors were already in Phase III clinical trials.

Yeah, I know of one for sure: Imetelstat and it made things worse. If people do not examine the literature and the results as a whole, then the myth that “telomerase causes cancer” will only propagate.

One other thing that is not a surprise: The researchers identified solar radiation as a common cause for melanoma-telomerase mutation.

Given the highly repetitive and highly vulnerable nature of the telomere (perhaps the most vulnerable chunk of DNA we have!) in particular the Thymidine residue which forms adducts with carcinogens with relative ease, and the Guanine which is super vulnerable to free radical damage it makes complete sense.

I hope the German study will lead to more help or even a cure for melanoma patients, but it will not be a telomerase inhibitor this I know for sure!

For all of us, the best policy is to keep our fragile telomeres long enough and healthy enough that we do not age prematurely and get these nasty diseases! Telomerase activation is one sure fire way to do that!

Dr Dave

PS as always I have over simplified some concepts here so they are easier to understand. It is not my intention to offend anyone involved in basic or clinical research but I do think Occam’s Razor applies here: the simplest explanation is usually the best!

Rat empathy, stress and telomere shortening

It may seem strange to tie all of these seemingly dissimilar things together but bear with me and all will be revealed.

As you probably know by now rats share many things in common with people. Some people more than others! There are similarities in biochemistry, structure and yes, behavior – all of which makes rats a good model for studying humans. Rats even seem to have shorter telomeres and slower erosion than some other rodents, again making them a good model for studying aging.

So what does aging have to do with empathy?

Well in rats if you take litter mates and expose one to some stressor in the presence of a litter mate, the litter mate also develops a stress response. Do that enough and you start shortening the telomeres of both rats. The presumed mechanism is excess secretion of stress hormones and the eventual deregulation of the stress response. The hormones involved initially are epinephrine and norepinephrine but eventually cortisol gets into the act.

Just like people!

The strange thing is that, at least hormonally, the rats develop these responses that mirror what we would normally assign as a human trait: empathy.

Also just like people!

Several different studies have been done in human beings to show the correlation of stress and telomere length.  The most telling of these involve the shortening of telomeres in mothers of sick kids and those responsible for caring for an Alzheimer’s patient in the family.  The stress mechanisms are put in place big time with all of our hormonal friends from above, epinephrine, norepinephrine and cortisol, showing up in the blood and urine.

The suspicion is that these hormones increase oxidative stress at the cellular level, accelerating telomere loss and increasing the percentage of critically short telomeres.  The net result is premature aging!

Remember telomere loss is actually the sum of two very different processes.

The first is the cumulative total of what I simply call lifestyle – how you sleep, eat, exercise, deal with stress and how much toxin exposure you get.  To some degree you can control and escape some of these slings and arrows that are thrown at you.

You can modify your behavior, limit your exposures, make sensible eating, supplement and exercise choices and modify your risk of premature aging.

The second is cellular replication. And while you may be able to slow that down, you never escape it.

The only way you can slow it down or reverse it is by reducing the number of critically short telomeres you have and possibly adding some length to those telomeres. In effect you are slowing, stopping, or even reversing the aging process.

The only proven way to do this in humans is TA-65, which of course helps with all the lifestyle damage as well.

I don’t know how much you value your life or those of the ones you love. Only you can decide if you personally are worth the cost. But I do know this. Stress kills and if you are caring for a parent, a child, a wife or husband that needs you, you might want to think about that as well.

Stay healthy, happy and productive!

Doc

Life without Twinkies – Calorie restriction and Telomerase

Bottom line of this whole blog:  Supplemental Telomerase Activation is Required for increases in Longevity whether you calorie restrict or not.

There are probably three or four studies now that show one simple irrefutable fact: you must turn on and increase telomerase expression to improve longevity. Most of them have come from Maria Blasco’s lab in Madrid Spain but the first one actually came from a lab in Texas by a fellow I have had the good fortune to speak with as well: Jerry Shay.

There have been a couple of ways to do this. Originally it was done with oncogene (cancer) promoters attached to the telomerase gene to turn it on. Ironically in these cells the experiment ended not because of cancer but because of boredom and expense.  Basically the lab tech pleaded for mercy after the number doublings (effectively the replicative lifespan) exceeded 700% normal. At that point the cells were mercifully sent on into the great beyond since they had become immortal already and new studies with new cell lines were begun.

What is the take-home message from this study?

Add in enough telomerase to healthy cells and you will get healthy immortal cells without cancer.

Since that time others have replicated the data and found more or less the same thing: Telomerase activation improves healthspan and if you turn it up high enough (but not to high! Remember Goldilocks – JUST RIGHT!) you also get longevity improvements.

There have been other interesting finds that point to telomerase being one of the major keys to health and longevity.

Dr Blasco’s lab pioneered the use of a non-cancer-causing viral vector called AAV9 which has some special properties when coupled with telomerase. First, it is trophic, meaning it gets into lots of different cell and tissue types and next, it is “non-integrative” which means it does not insert itself into the DNA (genome). Two things happen because of this.

First, these little “virosomes” churn out telomerase like little telomerase factories. But with each cell division the effect is diluted out. This is important because in the past some integrative viral vectors (those that got into the genes) caused ongoing expression of telomerase from embryonic age on and did increase cancer incidence in measurable if not massive amounts. The dilutional aspect of the AAV9 virosomes allowed them to be added in mouse “middle age” and old age and the increases in telomerase were limited in amount and time compared to the mice that were genetically engineered.

The result of AAV9?

Middle aged mice lived 24% longer old mice lived 14% longer. So it does appear in mice at least that earlier treatment results in more effects. Now I have to tell you that is actually the opposite experience that I have seen with TA-65 because often the fastest and most dramatic effects are seen in older people who ostensibly would need it more. Keep in mind that younger and middle aged people also can benefit tremendously and there is value in “preventative” telomere maintenance.

The other critical thing to note is: unlike calorie restriction it appears that not only does the “average mouse” live longer than its non-telomerase-activated relative but also the oldest of the old mice gain in lifespan.

So you can no longer say that calorie restriction is the only way to lengthen life. In mice it does not seem to work that way UNLESS you add in telomerase.

That is the result of Dr Blasco’s most recent paper released just today.*

Calorie restriction did not lengthen life in her mice. It did improve neurologic parameters and decrease the incidence of cancer and metabolic disorders, but the mice still died at the typical age of mouse death.

When you added in telomerase by the genetic manipulation, which normally causes cancer, the calorie restriction appears to reduce the cancer risk associated with the ongoing high level telomerase expression back to baseline.  Only problem: the mice were only 3 months old when the calorie restriction started, which equates to about 18 years old in people.  That is a long time without Twinkies!

I hope you understand the importance of all of this work. These scientists have identified the level of telomerase, the ways it can and should be expressed and the direct effects on longevity without causing cancer.

In addition, Dr Blasco has found a way to extend mammalian life span with and without calorie restriction.

It’s called telomerase.

Dr Dave

*In case you are wondering how I got all this info the same day the info hit the presses, I spent an hour on the phone with Maria Blasco today – something I get to do more often than most!

Lengthen Telomeres With Your Food Choices

One of the most vexing problems I face as an expert on telomeres and telomerase activation is the issue of diet and telomere length.  The problems come in many forms such as using vaguely related or truly unrelated studies to support an eating agenda, using poorly designed studies with inadequate measurements to claim positive results, and the complete lack of 3^rd party verification to support  statements.

Examples of these in order include: Paleo or Raw Food Veganism, claims made for Multi-Vitamins and telomere length and resveratrol as a telomerase activator. Each and every one of these things could be a blog in itself but for now let’s just stick with what we know about diet and telomere length.

First a diet rich in anti-oxidants supplemental or otherwise has been suggested as a good addition to any anti-aging program. But defining the specifics of that diet has not yet been done.  And as usual  there is contrasting results depending on who has done the study. Bottom line: makes sense but not proven.

Fortunately a recent study in Finland may help clarify this a bit more by tying fruit and vegetable consumption with telomere length. In women, vegetable intake was positively associated with white blood cell telomere length. Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits.

Here is what they found:  “ In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits.”

They also found that total fat intake and especially Saturated Fats were associated with short telomere length.  They tried to find an association with meat consumption ala the China Study but did not find it to be a dietary villain here.

It would be truly wonderful to do a full blown randomized placebo controlled study on diet and telomere length but this is almost impossible.  Getting people to live in a bubble for 12 months is going to cost you big time and the line of volunteers wouldn’t be very long.

Until then we have to live with the same old boring advice of eat more veggies, maybe some more fruit and avoid saturated fats.  This looks like it will slow down telomere loss and reduce the speed of aging.

This coupled with the reversal of short telomere length by TA-65 is a pretty compelling way to live longer and healthier!

Doc

Planning for Fido’s future- telomere length and doggie longevity

We sure do love our pets! For some people a pet is the culmination of everything they seem to want and need in a companion. As a matter of fact some people spend a life time searching for a partner that has the qualities of their pet. With unquestioning love, unflinching loyalty and total obedience to a furry sometimes goofy and very lovable appearance thrown into the mix, its easy to see why we spend billions on “man’s best friend’!

To put this in perspective for you, back in the day when I worked in one of the busiest practices in my city I would often make house calls on my shut in or terminally ill patients. I was always honored to be welcomed into their homes and they loved the fact that “Dr Dave’ son of Dr John who had cared for them for decades was coming to their home. That was a reward beyond anything monetary. And it’s a good thing too because depending on the situation Medicare allowed between $25 and $40 bucks for a house call.

When my Vet visits my home to care for my pets its NEVER under $500! The sad truth though is that in spite of the very best care, our dogs and cats live out their lifespans in a fraction of the time we do leaving us bereft of our best friends and searching for new ones.

But just as human longevity and health span have the potential to extend way beyond their present values, we may soon see the same promise for our pets.
You may have guessed this all centers around telomere length and the rate of loss in specific breeds and species. Speaking of species the main “pet friendly” species that age by telomere loss include dogs, cats, horses some species of birds and fish. As far as the rest of our pet species we really don’t know since most have not been studied.

A recent study in dogs pointed out some fascinating similarities and a few differences between man and man’s best friend in terms of telomeres and aging.

• In the 15 species of dogs examined, white blood cell ( immune cells) telomere length showed a strong correlation with longevity in that breed. In humans telomere length has also been equated to longevity.
• In the same species dogs with shorter telomeres had a higher risk of heart disease, just like people!
• Dogs are inbred, most people are not. People do indeed show variations in telomere length from birth based on both genetic and racial differences but the differences appear to be relatively small. The loss of telomere length due to cellular replication is relatively constant and much of the differences in longevity have to do with lifestyle, environmental and epigenetic differences rather than genetic differences. In dogs the inbreeding leads to wildly different telomere lengths. For example the Great Dane weighs in at 11.7Kb and the beagle at 27 Kb.
• These wide swings in telomere length are probably the main reason the Beagle lives much longer than the Great Dane on average.
• Telomere loss in dogs is accelerated compared to humans also accounting for their much shorter live spans than their masters.
• Breeds that tend to have more health problems than others can also generally be shown to have shorter telomeres to begin with.
• No studies have been done with TA-65 and dogs and I cannot recommend you start your pooch on it but I do know several people who have usually at a dose of 1 a day mixed in with wet food or given as a pill the way you would an anti-biotic. So far I have heard of no problems but if you want to do this you should run it by your Vet first!

Frankly as long as there are no safety issues I don’t see any reason why it would not work!

Now if you think about it the telomere length of the average dog, even a short lived one, it is a lot longer than the average human. So why do they lose so many more base pairs of telomere length than people do?

Again no one knows the exact answer but if you look at the anti-oxidant defenses of these animals you see that compared to humans they have fewer defenses against free radicals than we do. This makes their telomeres and everything else age faster than in people.

Another factor parallels people as well: lifestyle.

For instance a dog or cat that is strictly “outside” with no shelter or care will die a lot sooner than an “indoor” animal ( diet not withstanding) even when you factor out obvious trauma and disease.*
With all this in mind, there is no reason that improving your pet’s care and at some point adding in Vet certified anti-oxidants and telomerase activators will not help us extend the lifespans of our beloved pets.

So the next time you visit your retirement counselor, you might want to bring Fido with you!

Doc

Reference: http://www.cell.com/cell-reports/abstract/S2211-1247(12)00418-4#References

TA-65 demonstrates superiority in a head to head trial

I have said at least a dozen times, you need human studies to document the effect of something in humans!  While I freely admit there are probably a dozen or so compounds that turn on telomerase in the lab, TA-65 is the only one with human studies.

Recently an actual head to head study was released looking at the potency and biologic effects of TA-65 versus another reported telomerase activator.

Here is a summary of what they found – in cells from live people, not rats, not Petri dishes, not fruit flies:

*TA-65, but Not the other telomerase activator, Increased Telomerase Activity in All Donors’ T Cells during Primary and Secondary Stimulations.   This means that TA-65’s telomerase activity worked the first time and the last time and basically anytime, every time. It was reliable and repeatable; the other telomerase activator was not.

*Telomerase Activator TA-65, but not the other telomerase activator, Increases T Cells Proliferation.
T cells are your body’s defense against viral infections, cancer and other invaders. In previous studies TA-65 was demonstrated to decrease viral loads in AIDS patients and elderly people with a chronic virus known as CMV.  Activation of CMV is part of something known as the Immune Risk Profile and is pretty much a death sentence in older people. Again, TA-65 has proven to improve the immune response and decrease the viral titres.

*TA-65 increased Telomerase Activity in cells of all the participants anywhere from 30% to 300%; the other one did not.  This again shows the repeatable if variable nature of TA-65’s ability to turn on telomerase. Conversely it showed that smaller increases in telomerase activation were only shown in 30% of the study participants.

*This study showed that TA-65 rescues critically short telomeres, the drivers of cellular senescence (aging!). Other studies have shown it improves other measures of health such as glucose tolerance, osteoporosis and skin fitness and finally, restores the immune system (which I feel is the most important overall driver of aging and longevity) to a more youthful profile.

Bottom line: The other telomerase activator was not much of a telomerase activator.

If you are not on TA-65 and want to be, go here.

And remember, we wrote the book on Telomeres/Telomerase Activation: The Immortality Edge book.

If TA-65 is too much for you, then a great gateway product is the Telomere Edge Pack.

I do not claim it to be a telomerase activator because it has not been tested in humans, although several of its ingredients have shown activation in the lab. It’s a great Telomere Support Agent.

Through the efforts of myself and my co-authors, TA-65 is getting to be a household word. It works, it works all the time, every time and has several human studies including this latest one.

No one else can say that!

Doc

What Kind of Exercise is Best for Telomere Health?

There has been a lot of focus on “Long slow distance” (LSD) exercise and telomere health.  I have oft quoted the “German Runners Study” which was actually a paper presentation and not a fully published work at the time that it got so much press.  That study showed that men who ran at high levels (50 miles a week) had telomere length comparable to 25-year-olds.  It did not, however, address what other exercises they were doing, their supplementation habits, their family genetics and their overall lifestyles. More importantly it did not look at what their actual favorite distance was. If you run everyday, 50 miles a week boils down to about 6.7 miles a day.  Five days a week and you are at 10 miles a run.  These are not marathons, nor are they marathon training distances in most cases. Yet every marathon blog on the planet was saying “SEE! Marathons can make you live longer!” In point of fact, serious long term high level marathon training doesn’t even start until you hit about 70 miles a week and there is an association with cardiac dilatation, valvular dysfunction and potentially fatal cardiac arrhythmias, probably causing some of the famous “runners deaths” we read about from time to time. By the way, this is also seen in endurance cycling. I remind you, I have run ultra-marathons, which are often 3x marathon distance, but I have not done that my whole life and currently limit myself to 6 miles a run, maximum.

On the opposite end of the spectrum, telomere length and weight training have not been adequately evaluated with a large well controlled study. There is, however, data on grip strength, leg strength and overall power generation and longevity, all of which suggests you need some muscle and especially power (max force x min time = max power) to live long.

Additionally, there is a published study showing the benefits of “interval style” training for telomerase activation and telomere health.

For most people I still like this for getting in shape. In my practice, the LSD preselects out “people who can take it” because the only ones left standing are those with the genetics (and joints!) to tolerate the LSD. In addition, two other things to consider: 1) People will want to generalize this to “fit” their sport. I guarantee you this will wind up on marathon blogs as proof of the “healthiness” of running marathons or some other thing. It will also wind up on gym blogs as proof that “exercise is good for longevity and come buy a membership to our gym!” This study was about cross country skiing and while it was endurance, it is a very different exercise than long distance running. Remember as you get out your Dr Dave Voodoo dolls that I am an ultra-runner and am telling you I do not think it is healthy for most! This is one reason I take high dose TA-65! 2) The study does not address causality and we have no way of knowing that the long distance skiers do not do a lot of other healthy things that essentially preselect for longer telomeres and a better healthspan.  Finally, the fastest way to improve your cardiac fitness and VO2 max is interval-style training. This will help any LSD work you do if you do that because, contrary to popular belief, LSD does not raise VO2 max much at all! I run ultras because I like what it does for my brain and I enjoy the solitude of moving through miles of territory most people avoid – not because it is good for my telomeres!  Take your fish oil, Take TA-65 if you can and have a rigorous regular exercise routine that includes mobility, strength and endurance. And keep your eyes open for my two books that should come out towards the end of this year.

Thanks to Andy Newman for asking this question!

Doc

http://www.worldhealth.net/news/longer-telomeres-long-term-endurance-exercise/

P.S. – I have addressed this question before to Mr. S Kumar who was kind enough to read it and change his evaluation of my book on Amazon based on this reply.

Hi, thanks for your comment and concerns. Let me say up front that I highly doubt you are going to change your recommendation no matter what I say but there is justification and a citation below for interval training. I can find none for marathon running and telomere length but welcome the citation if you have it.

I think we have to be careful about too much interpretation of the data on some of these studies. For instance, if you read the most quoted “German Runners Study” you will find most of the elderly (51 is elderly!?) runners were not marathon runners specifically. This has been reported differently on web sites and blogs to include marathoners, half-marathoners, triathletes and even used to justify weight training. They were in fact a mixed group of athletes who ran an average of 50 miles a week for the bulk of their adult lives but many were not marathoners. As a matter of fact, the word “marathon” is not mentioned in the study at all. In addition, there is a difference between WBC telomere length and skeletal muscle telomere length and the results are often opposite. (See Below)
I have included some references and posts below that may point you to a different conclusion or to at least be open to other options.
If you are looking for a randomized, double-blinded, double dummy, placebo, gold standard, you will not find it for any exercise or diet or meditation in humans.
Also, one needs to be careful about studies that use only TRAP assays for telomerase as a surrogate for lengthening telomeres, as this is not always the case.
Thus, when one writes a book on cutting edge topics, sometimes one has to interpret based on their own experiences and findings. Or we could simply have waited another 25 years to write the book, but even then much of this will remain unproven in the randomized, double-blinded, double dummy, placebo, gold standard sense, since those studies are extremely expensive and unaffordable for anyone but drug companies who do not stand to gain from the answers to the above questions.
The logic behind choosing interval training for much of the programs in the book is based on the following AND the information included below.
1) VO2 max can be trained up fast with interval training and this (V02 max) correlates with mean telomere length. You may be familiar with the study where experienced interval-trained individuals who were non-runners trained for 12 weeks for a 10K distance and outperformed people who had been running 10K’s for a long time. Exclusively training distance, as so many runners do, is not the best way to achieve total cardiovascular fitness. Also, if done properly, interval training can be done at high intensity with low trauma (deep water pool sprints) allowing even injured people to do it.
2) This was a book for ‘everyman and everywoman’, not specifically athletes or runners. This means the program had to be doable for the average person in terms of time commitment and results. Giving the average non-runner a running program did not fit the goals of the book. Nor would it achieve the results people are looking for, including us.
3) Go to any running club and you will find a large volume of chronically injured runners there. I am a sometime marathoner and ultra-marathoner as well, and my experiences have taught me this is not the healthiest thing to do from a musculoskeletal standpoint.

Again, see #1 with regards to injury.
4) There is a study below on interval training but I could not find any on marathon runners except with regards to shorter telomere lengths and overtraining syndromes.
5) I am an Internist/anti-aging doc and, while I am not a basic science researcher, I have checked telomere lengths in my athletic clients in the past and I have found the MTL to be longer in general in the cross trained individuals than people who just run. Again, this is not a RDBC study by any means but a clinical impression which should be worth something to a reader.
6) Now that the Life Length assay is available, we have a much better tool to assess these findings but don’t hold your breath for any of the above studies to be repeated any time soon. Again, funding is everything in science.
I think in terms of bang for buck, time wise and damage wise, interval training is a great place to start for most people since the oxidative stress is far less even though the intensity is far higher.
It is important to actually read studies and not just abstracts, blogs, online/newspaper articles because they often get the facts wrong. Since the “german runners study” I have seen that very article used to justify all different forms of exercise from yoga to Pilates to dancercise, etc. That is clearly not what it says. In addition, that article did not control for the most important confounding variables such as what else do people who run 50 miles a week do for their health/telomeres that sedentary people do not do – sleep, other training, supplements, maintaining body weight, etc. As such it is an observational study and does not establish causality. Then again, very few studies do on this or any other topic – so again, clinical acumen/experience is the surrogate.
I would love to see more research done here and if you have 5 million dollars to donate I will see it gets put to good use and answers these questions definitively!

Finally, let me say that for a good deal of the last 10 years I have run long and ultra-long distances. No one would be happier if long distance running were the ultimate telomere life preserver. But at this moment we can’t say that unless you know of studies I do not. I remain open to be educated.

Best,

Dr Dave

May 28, 2010
Bursts of Vigorous Activity Appear to Be a ‘Stress-Buffer’
FRIDAY, May 28 (HealthDay News) — Short bouts of vigorous exercise (interval training) can go a long way to reduce the impact stress has on cell aging, new research reveals.
Vigorous physical activity amounting to as little as 14 minutes daily, three day per week would suffice for the protective effect to kick in, according to findings published online in the May 26 issue of PLoS ONE.
The apparent benefit reflects exercise’s effect on the length of tiny pieces of DNA known as telomeres. These telomeres operate, in effect, like molecular shoelace tips that hold everything together to keep genes and chromosomes stable.
Researchers believe that telomeres tend to shorten over time in reaction to stress, leading to a rising risk for heart disease, diabetes and even death. However, exercise, it seems, might slow down or even halt this shortening process.
“Telomere length is increasingly considered a biological marker of the accumulated wear-and-tear of living, integrating genetic influences, lifestyle behaviors and stress,” study co-author Elissa Epel, an associate professor in the University of California San Francisco (UCSF) department of psychiatry, said in a news release. “Even a moderate amount of vigorous exercise appears to provide a critical amount of protection for the telomeres.”
Appreciation for how telomeres function and how stress might affect their length stems from previous Nobel-prize winning work conducted by UCSF researchers. Prior studies have also suggested that exercise is in some way associated with longer telomere length.
The current effort, however, is the first to identify exercise as a potential “stress-buffer” that can actually stop telomeres from shortening in the first place.
The team found that those women who were experiencing high levels of stress but were deemed “active” did not have shorter telomeres, whereas similarly stressed participants deemed “inactive” did.
Going forward, the study authors said that more research incorporating larger patient samples need to be conducted to confirm the findings and arrive at definitive recommendations for how much exercise might be needed to derive such cellular protection.
Eur J Appl Physiol. 2010 May;109(2):323-30. Epub 2010 Jan 26.
Skeletal muscle telomere length in healthy, experienced, endurance runners.
Rae DE, Vignaud A, Butler-Browne GS, Thornell LE, Sinclair-Smith C, Derman EW, Lambert MI, Collins M.
Source
UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Dale.Rae@uct.ac.za
Abstract
Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running(r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRFlength, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.

Med Sci Sports Exerc. 2003 Sep;35(9):1524-8.
Athletes with exercise-associated fatigue have abnormally short muscle DNA telomeres.
Collins M, Renault V, Grobler LA, St Clair Gibson A, Lambert MI, Wayne Derman E, Butler-Browne GS, Noakes TD, Mouly V.
Source
Department of Human Biology, University of Cape Town, South Africa. mcollins@sports.uct.ac.za
Abstract
INTRODUCTION/PURPOSE:
Although the beneficial health effects of regular moderate exercise are well established, there is substantial evidence that the heavy training and racing carried out by endurance athletes can cause skeletal muscle damage. This damage is repaired by satellite cells that can undergo a finite number of cell divisions. In this study, we have compared a marker of skeletal muscle regeneration of athletes with exercise-associated chronic fatigue, a condition labeled the “fatigued athlete myopathic syndrome” (FAMS), with healthy asymptomatic age- and mileage-matched control endurance athletes.
METHODS:
Muscle biopsies of the vastus lateralis were obtained from 13 patients diagnosed with FAMS and from 13 healthy control subjects. DNA was extracted from the muscle samples and their telomeric restriction fragment (TRF) or telomere lengths were measured by Southern blot analysis.
RESULTS:
All 13 symptomatic athletes reported a progressive decline in athletic performance, decreased ability to tolerate high mileage training, and excessive muscular fatigue during exercise. The minimum value of TRF lengths (4.0 +/- 1.8 kb) measured on the DNA from vastus lateralis biopsies from these athletes were significantly shorter than those from 13 age- and mileage-matched control athletes (5.4 +/- 0.6 kb, P < 0.05). Three of the FAMS patients had extremely short telomeres (1.0 +/- 0.3 kb). The minimum TRF lengths of the remaining 10 symptomatic athletes (4.9 +/- 0.5 kb, P < 0.05) were also significantly shorter that those of the control athletes.
ANOTHER REPORT
“These findings suggest that skeletal muscle from symptomatic athletes show extensive regeneration which most probably results from more frequent bouts of satellite cell proliferation in response to recurrent training- and racing-induced muscle injury.
The vast majority of research on exercise and telomeres points towards cardiovascular exercise as the key component needed to protect telomeres. It is clear moderate intensity aerobic exercise should be a component of training for telomere health. However, other studies have shown that chronic stress coming from excessive exercise or excessive stress may be the major cause of telomere dysfunction. This may be an issue when you consider chronic exercise such as marathon training, which raises cortisol without the benefit of growth promoting hormones. A brand new study in the journal Hormones (volume 8 #1) has shown that a relative excess of cortisol and insulin compared to the anabolic hormones HGH and testosterone plays a key role in telomere damage.
Shorter more intense exercise does a better job at balancing this hormonal equation, and therefore it may have a central role to play. Researchers studying this issue have also noted shortened telomere length in exercisers and athletes suffering from exercise related fatigue and in long-term competitive endurance runners. The May 2010 issue of the European Journal of Applied physiology showed endurance runners compared to healthy sedentary individuals have telomere lengths inversely proportional to the amount of running they did. In other words, the more mileage they accumulated over the years, the shorter their telomeres. It is interesting to note, even with all the exercise they did, their telomeres were not significantly longer than the sedentary non-exercisers.
This same issue was looked at in a group of competitive power lifters. In the January 2008 issue of Sports and Medicine in Science and Exercise long-term weight lifters were compared to a group of healthy active individual who were not weight lifters. There was no detriment seen in the weight lifting group in terms of telomere length, but they too had no significant advantage over the healthy active controls. However, the vast majority of other studies show exercise does provide an advantage. So what do we make of these results and studies? Exercise is protective to telomeres but excessive exercise may actually be a detriment.”

Measuring Telomere Length – The Long and Short of It – Featuring “The truths, lies and drama in the slam dunk world of Your Longevity Markers!”

Warning: this blog is long, somewhat complicated, very controversial, likely to make me enemies, likely to be 100% true and an honest reflection of my personal experience and likely to alienate anyone with a different agenda!  So be it.  Try to focus long enough to read it all, because it will do your telomeres a world of good and let you see a part of the world that “They” try to hide from you.  And this time “’They’ is not who you think!”

If you are in too much of a hurry to lengthen your telomeres, know this:

1) Longer telomeres are better than shorter ones.

2) The percentage of short telomeres is by far the most accurate way to determine your real biologic age.

3) If you really are doing the “right stuff” in your anti-aging program, it will show up as a “good” short telomere value and may not show up at all, with a median telomere value.

4) The Life Length assay is the only one that will tell your percentage of short telomeres – no other test on the market can do this.

5) A single test is a good thing. Two or more at regular intervals is a GREAT thing in deciding how old you really are and whether you are successfully combating aging (or, if you prefer, aging gracefully).

I have been both fortunate and fascinated by the topic of Telomere Testing. Fortunate in that I have been able to see the future of this technology first hand and talk to the people who created it, use it and improve it, on what has become a daily basis. I am speaking of the Life Length “short telomere” test.

The technology is fascinating, because among other things, it looks at hundreds of thousands of your individual telomeres, in tens of thousands of cells, in a small easy-to-obtain sample of your blood.  And while we are on the topic of blood, this is the only sensible way to measure your telomeres at present. It is the only way you get a close look at your immune system and how old it really is, while figuring out how old you really are. This may figure heavily in how great your risk of diseases of aging, like cancer, heart disease and infection really is.

You can see the test in action, because I filmed my own very recent Life Length Telomere Test and posted it on Youtube.

What is even more fascinating to me, is the resistance of some of the top scientists in the field in embracing this new technology.  I did not understand, until I realized that some of them were personally involved in another company with “competing technology”.  Now you may think that scientists are beyond bias and reproach in formulating their stance.  I found out in watching this whole drama unfold, that they are just as subject to the same emotions and weaknesses that the rest of humanity is – in spite of their intellects.

I will not name names, but here are some of the things I witnessed.

One super famous telomere scientist, who is involved in a commercial telomere testing venture, said he/she basically frowned upon business and found profit as a motive, repugnant. Now understand this is my verbiage, not his/hers, but it’s pretty dang close. That statement was rapidly removed from said web site, by someone who understood this kind of “anti-business” attitude will not stand on a business web site! This individual also said in a recent article that “short telomere testing has limited clinical value”.

This individual’s partner, another preeminent scientist was asked in a recent presentation, “What do you think of Life Length’s short telomere testing as developed by Maria Blasco?” Answer: “That seems to be the way the field is headed.”  Now to me, this is a quintessential scientist, because the answer was unbiased and irrefutable!

Yet, another top scientist stated that “median telomere testing was still the gold standard – not short telomere testing”. Same said scientist published an article, almost a decade ago, stating the shortest telomere, not the average telomere length, was the determinant of cellular aging.  Talk about an “about face!”

So there seems to be two camps on this issue and truthfully there is a lot of bias and opinion, to the point where some people are actually reversing the results of their own research, to support a certain agenda.

To me the “rightness” of short telomere testing is already proven and already established as the gold standard. I will tell you why I say this in a minute, but let me show you one more interesting and fascinating about face.

There are not that many companies that do telomere testing to begin with. One of the long-established technologies is called qPCR .  This technology is the basis for a saliva (spit) test that is planned for release, as soon as the first quarter of 2013. In their last press release, the very last sentence said, “And we’ll also be developing a short telomere test”. This company is made up of some of the same person/people who said it was not relevant and of limited clinical value.

Why are you all of a sudden about facing and saying you will be doing it too?! Maybe because that is the way the field is headed! To me that makes it very relevant and of great clinical value.

Ok, now you know the politics of short versus mean or median telomere testing.  Bear with me while I add my personal voice (yet again!) to why I think short telomere testing ala Life Length, is the most important discovery and technology to come along in a long time and should supplant any other measure of telomeres from now on.

First, it does give you median telomere length in an extremely accurate fashion, far more so than other technologies like PCR and even FLO-Fish.  If you go today and use the Life Length assay and then decide to go again in two weeks (there is no reason to actually do this, so be aware it is for illustrative purposes) you will get the same numbers for both median and percentage short telomeres, or extremely close.

With the other commercially available technologies you may see up to 1000 base pair variations in your telomere length. This is equivalent to 10 years difference! So you might find out today you are 5 years older than your stated age and in 2 weeks you could be 5 years younger. Wow, that is magic, right!  Nope; sadly, it’s inaccuracy.

Also, keep in mind that the Life Length assay is the ONLY commercially available test that will tell you your percentage of short telomeres.  And if you believe, as I do, in all the science that supports short telomere testing as the New Gold Standard, YOU personally want to know this number. YOU personally want to know where you really stand – what your real biologic age is and then of course what you want to do to improve it.  The Life Length assay can be reasonably repeated in as short a time as 6 months if you are on an aggressive telomere maintenance/ lengthening program.  Let’s face it; taking care of your telomeres is not a cheap proposition. YOU should want to know where you stand for real and whether you are doing the right stuff to fix or maintain these biologic time clocks. And, you should want a REAL number measured by looking directly at YOUR telomeres, not some calculated number generated by a probe.

You don’t get that from the other measurements, because none of them measure short telomeres.

NONE of them! This is why some of the individuals who are involved in competing technologies are racing to embrace this new technology.

Let me give you some individual results that I have seen in the testing I have done.

As you might guess, a lot of doctors want to do this testing. Many are so sure that they have done the right things to be healthy.  Most are not smokers, drink moderately, if at all, and almost all of them claim to follow a good diet and exercise regularly.

Well, as it turns out, many of them I have seen, have a higher percentage of short telomeres than normal, indicating an “older” biologic age than their actual age. In other words, doctors are among the most unhealthy people you’ll meet.

This usually provokes the response “THIS TEST MUST BE WRONG”. Then you ask them about stress and stress management. Then you ask them about sleep deprivation. Then you ask them about their residencies and their practices and their personal stresses and they have an “AH HA!” moment.

You see there is no free lunch. Mother Nature and Father Time don’t care whether you accumulate a lot of short telomeres in residency training program in your 20’s, or whether you do it in your 60’s. You pay the price of tough childhoods, tougher pregnancies, crazy exercise endeavors (Like the Canadian Death Race I have run!), lousy diets, middle aged Baby Boom New Year’s bacchanals, high stress American Dream jobs, the abominations of Big Pharma, Big Food and your and my own misdeeds!

Once you lose telomere length and accumulate short telomeres, a telomerase activator like TA-65 is currently your only option to fix those short telomeres.  Telomere maintenance, as with my Telomere Edge Packs, or the many multi-vites described as “telomerase activators” that have come to the market as copy cats, is also a valid option for many, who chose not to activate their telomerase for whatever reason.

But, for many more than you would realize, the Bottom Line is, all of a sudden, a few thousand dollars a year to help your biologic time clocks, does not look so expensive after all. All of a sudden, it looks better than a 4G portable internet service, a big screen TV with FIOS or some other technologic masturbation that you have to have, that costs you thousands a year and kills off your brain cells.

The usual scenario I see is that someone has already had one of the other abovementioned telomere tests that does not include short telomere measurements. They are often convinced they are “OK” because their median telomere length (the only thing you can get with the other tests) is close to, or better than their actual age. They are unsettled to find that often, they have a high percentage of short telomeres.  All of a sudden they are forced to honestly evaluate their anti-aging programs and revamp them.

Here are a few examples.

Subject A was a mid 50’s male physician who claimed to eat healthy, exercise hard and take a lot of supplements. He was not on TA-65 because his median telomere length as measured by qPCR, was a few years “better than his actual age”. Specifically he was 45 years old based on his median qPCR telomere length and his actual age was 52. Naturally, he was very proud of his superior make up and anti-aging program, which included hormone replacement and the most magical supplement of all, Vitamin D. Notably, he was on very low dose fish oil, no CoQ 10 at all and no glutathione, or glutathione precursors like N- Acetyl Cysteine.  He looked lean, although he lacked muscle. His diet was primarily vegetarian and he ran 6 miles, 3x a week.  He did not train with weights or do any resistance training, because “all the data point to aerobic exercise as the best”.  I won’t get into why this is not the best practice here, but if you haven’t read our ground breaking book, “The Immortality Edge,” you should, because we explain it all there.

This doc was shocked when his short telomere percentage showed him to be 60 years old!  At first he didn’t believe it, but then we went through all of the stuff I mentioned above. Ultimately, he was grateful for the information and made several changes to his routine, including much higher doses of fish oil which corrected his abysmally low Omega 3 level and you guessed it, Telomerase Activation with TA-65 at high doses.

But it works the other way too!  I got an incredulous phone call from a European doc basically saying, “How do you explain this!”  She was contemplating putting one of her patients on TA-65 and was sure he was a dead man walking. This guy barely exercised, kept no dietary restrictions, drank enough to be considered alcoholic and by rights should have had the shortest telomere of any person on the planet!!!

He was 60 years old, chronologically. His median telomere length was almost exactly at 60 years of age but his lower than average number of short telomeres put him at about 52!  How could he be getting away with it and what should you say to him next!

Well again, the detailed questionnaire that comes with the test tells the tale. In spite of this guy’s habits he is an optimist and under no stress. His grandparents died at 92 and 102 respectively and both his parents are alive, relatively disease free and active in their mid 80’s. And they both drink a lot!

So, this is one of those super lucky people who were 1) Probably born with longer than average telomeres 2) Probably has a superior antioxidant defense system, naturally 3)Has great genes and maybe even one of the super lucky people who have a variant telomerase that keeps his telomeres longer.

Now, you have the embarrassing situation of what to tell this guy, who breaks every rule and gets away with it!

Here was my advice to this doc, “Tell him he’s lucky, but don’t push it. Still try to get him to do exercise and drink less, because at some point it will catch up to him, although maybe much later than the rest of us! Make the most of your blessings and don’t abuse them and a low dose of TA-65, like one a day, is a great option at his age. And, oh yeah, check his Omega 3 levels, just to be sure”.

The final most important point to make is this: You should get another test in one year to at least establish two data points; now, and a year from now. Because, if you suddenly see a big increase in short telomeres, you know his “luck” has run out and he needs to behave like the rest of humanity to have a good shot at a long life and great health.

The final case I want to share with you is one that is public. As a matter of fact, it was picked by “Cell” magazine (yeah, it’s one of my favorites!) as one of the top articles of 2012. It tells the story of a famous scientist in the field, who decided to use the short telomere assay. He found a median telomere length that was “normal”, but had a significantly high % of short telomeres. Subsequently, he had his genome sequenced and found he had an unhealthy variant of telomerase, that was likely the cause of his worse than average biologic age.

Had he relied only on median telomere length technologies, he would NEVER have known that and never found his problem. Armed with this knowledge, he can decide how to fix it and knows to follow up with another short telomere assay soon. There is no other way he would have gotten what could be potentially life-saving information!

As I said at the beginning, there are some people out there who are going to be very mad at me for this blog. I am not trying to discredit anyone, or to disrespect anyone’s achievement.

But, I call them like I see them and short telomere testing is a homerun and that’s the long and short of it!

For more information about short telomere testing in the U.S. contact ADL Tests, or specifically yenvy@adltests.com

Dr Dave

P.S. I should add that the real thing that scares me is, much of the early work in the field was done using these inferior tests and that a huge database has been generated this way.  While it’s true that statisticians can sort out problems more clearly with big databases, there are bound to be some very wrong conclusions and underestimations of the importance of short telomere in these works. I think every major study in the field should be redone, using short telomere testing – at least in those studies that involved people. Barring that, only short telomere testing should be considered in future human studies. Remember, you get a median telomere length anyway with this technology and you actually look at real telomeres on real chromosomes like yours and mine!

PSS – If you want more science, read these!

http://www.cell.com/cell-reports/fulltext/S2211-1247%2812%2900263-X?switch=standard

http://www.ncbi.nlm.nih.gov/pubmed/11595186

PPSS I am not a paid employee of Life Length! I paid for my test (I actually paid more because I went to Madrid to have it done so I could tour the lab. The Euro vs. dollar exchange rate sucks – hence my higher price!). I don’t get a dime for this, but I am so convinced this is beyond valuable info, I share it with you so you can make your own decisions. I want you to be around to read my blogs a hundred years from now!

The Truth about Telomerase activation and Resveratrol – The Long and Winding Road

I find myself saying the same thing over and over again and I still see the same baseless assumptions all over the internet. So, with my usual cut-through-the-BS attitude, I feel compelled to do what is necessary to protect the truth – YET AGAIN!

There are several misconceptions that continue to float around in the lay press/public about telomerase and cancer.  One is the mistaken assumption that telomerase somehow causes cancer, which arises from several seemingly viable sources, but fails under scrutiny. This is the danger of the internet. Someone who states something authoritatively becomes an authoritative expert and the misconceptions spread.

Simply, cancer makes telomerase, not vice versa. It makes it by gene amplification, mutation over promotion and all kinds of unnatural ways that are germane only to the process that creates cancerous transformation in the first place.  There are at least 3 cellular check points that have to be overcome, including the DDR (DNA damage response) P53/21 system and several others as well. Once that happens, in the presence of critically short telomeres, or processes that critically shorten the telomere, which are similar to the processes that cause cancer – mutations, oxidation, inflammation, etc. from all the various sources, telomerase can be massively over induced to sustain the already damaged genome of the cancer cell and allow it to divide far more rapidly than noncancerous cells.  Studies on villous adenoma have suggested that telomerase induction is the very last step in cancerous transformation. Inhibiting Telomerase will always fail as an anti-cancer measure, because in removing the telomerase positive cancer cell population, you either unmask or induce ALT telomere lengthening and the cancer comes back worse than ever. Imetelstat and other telomerase inhibitors have failed, probably because of that reason.

This must be the 1000^th time I have said it, but telomerase is not oncogenic, unless it is constitutively massively over expressed. In 2002, Jerry Shay’s group created an immortal cell line with the worst possible vector – a RAS oncogene promoter.  The cell line doubled over 500X (normal cells quit after 70) with no evidence of cancer.  The cells died a quite death when the lab assistants got tired of feeding them – since they had effectively proved a point. Maria Blasco’s lab extended mammalian lifespan (mouse model) by 24% with the AAV9 non-integrating vector. No increase in cancer.  She also used the nutraceutical TA-65 in a different study for only 3 months and improved multiple measures of healthspan in a similar mouse model.  No increases in cancer.  Ron DePinho did a similar experiment reversing the phenotype of aging in his mouse model, using a tamoxifen trigger to express telomerase.  No increases in cancer.  A  JAMA study in late 2010, showed an association of short telomeres with more and worse cancers, and most of us feel that canonical activation of telomerase in cancer patients is a good thing, since things like TA-65 have been shown to improve the immune system, by restoring naïve active CD 28+ helper cells which fight viral infections and cancer to normal levels, reverse bone density abnormalities, reduce the markers of inflammation, restore collagen and elastin balance to the skin and many other biomarkers of aging. In a cancer patient especially, the immune function benefits would be huge, since this would be the way to fight off the ALT-based cancers and the amount of “extra telomerase”, expressed in the normal fashion pales in comparison to what the cancer is already doing without driving the cancer forward.

Now, here is the study I hope to fund soon.  We have extended mammalian lifespan as noted above. It is not rocket science to imagine that in doing so you must improve cellular repair processes, including mitochondrial function,  proteasome regulation, mTor, Sirtuins, intracellular junk, glycation, ubiquitination and so on and so forth – all the “theories of aging” or the organism could not possibly survive longer with all that dysfunction. Telomerase must reverse some of it, for at least a while. No one has done that particular study yet, but I am working on it.

You don’t need to genetically re-engineer the telomere to do this, unless you have a telomeropathy like IPF, one of the Progeriod syndromes (Lamellin has now been shown to critically damage or shorten telomeres) or aplastic anemia to begin with. To reduce the aging process and improve healthspan and lifespan, you need to genetically or pharmacologically improve the telomerase enzyme. It remains to be seen whether you can pass the Hayflick limit in humans this way, but it should be possible, since it has been done in mice, although no one has interviewed every mouse on the planet to see which one is the oldest!

Telomere erosion is based on two main things – cellular division and loss of telomere length (telomerase responsive) and toxicity to the telomere from lifestyle, environment, etc. (also telomerase responsive).  The inherent damage to the genome via defective repair from the DDR is always a concern, but as long as the cellular checkpoints are intact (also, you guessed it, telomere/telomerase dependent) those cells will be removed by your effective intracellular check points and your far more effective immune system. That is the current thinking, which is more than speculative, but not yet proven. Honestly, I think we should be glad we are alive now, because it is pretty promising.

Next:  Resveratrol’s action on SIRT1 is via adipokines – not direct action. The SIRT 1 protein is located in the mitochondria and its action is there – thus anything that depends directly or indirectly on SIRT1 effects mitochondrial function. The main regulators of mitochondrial function are the PPAR Co Factors, specifically PCR1 alpha. As was shown by both Passos and DePinho independently, these co factors are regulated by the P53/21 systems, which are in turn directly regulated by telomere length. Subsequently, they showed this regulation included the following mitochondrial behaviors: biogenesis, mtMutation rates, and ECT function, all of which “got worse” as the telomere shortened and apoptotic/senescent signals accrued. Ultimately, this was extended to include senstatic activation, now referred to as SASP (senescent activated secretory phenotype) resulting from mitochondrial dysfunction and ROS/NOS leakage with subsequent immune response.

Sirtuin expression has also been shown to be directly related to telomere length, so stop looking at resveratrol for longevity. It is a good antioxidant that has promise in treating -based disorders like diabetes, metabolic syndrome and obesity, all important. But, in spite of reports of telomerase activation, which cannot be reproduced by the best lab in the world for that sort of thing – Bill Andrews’ Sierra Sciences – it is not a telomerase activator and therefore not a longevity drug.

But if you are fat, by all means take it! Just don’t expect to live longer because of it.

http://www.nature.com/news/2011/110921/full/news.2011.549.html

http://www.ncbi.nlm.nih.gov/pubmed/20188786

Why you may have short telomeres

Note the abbreviation “kb” means kilobases as in thousands of base pairs. So 3 kb = 3000 base pairs.

At a conference I spoke at recently, I was asked why telomerase does not replicate the “full DNA duplex of telomeres”.  I was not sure if they were asking why telomeres shorten, if there is an enzyme that can lengthen them, or why does telomerase leave a single stranded end known as the “T loop”.  I decided to answer both questions, since there are a lot of good instructional points here.

First, the full DNA duplex of telomeres is just a weird way to phrase something.  DNA is usually coiled in a compressed  2 stranded structure known as a duplex (two strands).  To me the “full DNA duplex” means the whole kit ‘n caboodle of the whole bloody chromosome. Technically, the telomere is no longer double stranded at the end, so that confuses things more to me. Don’t you just love how science can get complicated way beyond what is necessary, because of the word choices!

So, speaking of choices, I had no choice but to launch into a “double stranded duplex answer”—in other words, I gave two answers.

Let’s start with the shortening  issue first.  In normal DNA, there is what is known as the end replication problem. DNA polymerase may be physically too large, or functionally “kicked off”, as it approaches the telomere strand, as DNA polymerase is unable to complete the replication of the telomere. Instead, the enzyme “Telomerase”, which is an RNA reverse transcriptase, is active in some cell lines, primarily germ, stem and some rapidly replicating somatic lines. The degree of activation determines the degree of telomere shortening, maintenance, or lengthening.

In most cases, telomerase activity is not sufficient to add length to the total telomere mass, nor does it attempt to. In most cases, any telomerase activity that does occur, appears to be focused on the short telomeres (variously defined as less than 3-5kb) only. In some early stage progenitor lines, there does appear to be enough telomerase activity to prevent loss of the mean telomere length as well, so the trigger for telomerase binding/unbinding may be different or set at a different point. Telomerase over expression has recently been used to extend mouse life span (Blasco 4/2012), with no evidence of increasing cancer, or loss of cell cycle checkpoints.  In most cases however, there is simply not enough expression, as the enzyme is repressed and telomeres don’t lengthen – they shorten and induce cell cycle checkpoints, leading to senescence or apoptosis.  This is probably part of the function of the single strand end known as the T loop, since this appears to be where telomere erosion appears first. Which brings us to:

Why telomerase leaves a single strand end unpaired, that ultimately curls over on itself and binds to a displaced double strand of DNA, that loops out to “catch” the free end and form the “D loop”, which is technically triple stranded.  No one knows, but from a design standpoint, with reference to the above cell cycle check points, it looks like this structure is part of the “time clock” function of the telomere. Having the free end tied up, prevents the DNA Damage Response (DDR) from treating the telomere end like a double stranded DNA break, which would incite senescence or apoptosis, even with a long telomere.  As the telomere erodes and shortens, the D loop and T loop structures are eroded and at some point (again variously described as 3-5kp) the telomere is short enough to cause a DDR and stop replication.  At this point, someone usually starts talking about “telomerase causing cancer”. It should be noted that this is not a satisfactory explanation, since telomerase does not cause cancer. Cancerous changes occur and it appears like the last step is the immortalization of the cancerous cell line, by massive over expression of telomerase. But the changes occur first and cause the telomerase over expression, not vice versa. The sad failure of Imetelstat is but one example of the fallacy in the “cancer causes telomerase” theory.  You may inhibit telomerase, but you then select out the remaining cancer cells that use the other way to lengthen telomeres, ALT and you get a recurrence that is worse and less treatable than the original cancer. If telomerase was a cause of cancer, telomerase inhibition would cure it. More and more, it looks like having a lower percentage of short telomeres and a longer mean telomere length, stabilizes the genome and prevents DNA damage. Thus, telomerase expression may actually protect from cancer.

In the long run, there are two simple (meaning I am simplifying this greatly) reasons telomeres shorten and they are causally mutually exclusive of each other – which means the “treatment” is also mutually exclusive.

First, telomeres shorten naturally with each replication of the cell, unless telomerase is around to prevent that by adding more base pairs. The only way to do this safely in humans is TA-65.  This is the only telomerase activator with real human data.  Rumor is, some “other” telomerase activators are undergoing human trials, but I am willing to bet the results will be reported in the presence of several other compounds made by this MLM company, not solely. Especially if it turns out, as another rumor has it, that this compound is inferior in telomerase activation to TA-65. They will want to get something for their money, so count on other “biomarkers of disease” being used, if the telomerase activation doesn’t look good, or they might simply leave out the comparison to TA-65 and not mention it at all.  That should be a clue!

Next, and independent of cellular reproduction, is the ongoing damage to the telomere that happens as a result of oxidative damage. This can be from oxygen or nitrogen free radicals and some other less common forms of free radicals. The telomere has a DNA molecule in it called Guanine, which is extremely sensitive to oxidative damage. In this case, there are many good antioxidants on the market that may help. My personal favorite are my own purpose-designed Telomere Edge Packs, naturally.

We covered a lot here today and I hope it helps broaden your understanding of what is surely the most important discovery in human health and longevity so far.

Doc

Does being a fitness fanatic make you live longer?

I will use the standard marketing style — “Yes, but it’s not what you think!” In order to effectively answer your question, I think we’d need to define fanatic and that of course is subject to interpretation.  The obituaries are peppered with athletic superstars dying before their age.  Grete Waitz died at 57 of cancer. Jim Fixx died young of heart disease. Micah True, the legendary trail ultra-runner and one of my personal heroes, died in his 50’s with ‘idiopathic left ventricular dilatation’ (a pathologically enlarged heart).  But, it is not just long distance runners.  Vasily Alexeev, the Russian super star weight lifter, died of heart disease at 69.  What people seem not to want to talk about is that, especially endurance athletes, develop dilated cardiomyopathy that predisposes to potentially deadly irregular heartbeats. While I was always loathe to believe that these were nothing more than coincidence, I no longer feel that way, now that I have spoken to several sports medicine docs. I think that very high level endurance athletes in particular, are at risk for this compensatory dilatation that predisposes them to potentially deadly arrhythmias. No one knows for sure though, if they had genetic predispositions, as well to irregular heartbeats or heart disease.  In the case of Jim Fixx, who died of garden variety blocked arteries in his late 50’s, we do know his father died at age 43 of pretty much the same thing. So, you could make the argument that running added 15 years to his life, if you wanted.

So, bottom line: “fanatic exercise” is probably not conducive to any survival advantage and probably the opposite.

But, there is stronger evidence that moderate to intense exercise, short of fanaticism, is actually good for you. If one uses telomere measurement as a biomarker for life span, which is getting to be more and more obvious, even to the most hard core nay sayers, there are some interesting studies.

The first is the “German runner’s study” where middle aged (the study, in a throwback to days gone by, said “elderly”, but the average age was 51!) chronic runners who did about 50 miles a week for most of their adult lives, had similar telomere lengths to young sedentary (25 year olds), non-athletes and young athletes training at a similar level. This has been used by just about everyone with an exercise agenda, to justify that agenda.  In particular, marathon people love to call them marathon runners, but the study does not even use the word marathon and most marathoners would agree 50 miles/week is pretty low level for a serious marathoner. Triathletes call the German runners triathletes, yoga aficionados say it proves yoga is good for you, and on and on. But that is not what the study said. It says that long term, vigorous activity, in this case 50 miles a week of running, is a telomere preserver. What is not clear is what else these runners did in terms of training. Supplements, hormones, eating, sleeping, etc., etc.  It’s common enough to see fit people doing a lot of other things conducive to fitness that are not measured. So basically, when you find a group of people who’ve dedicated themselves to fitness, for that length of time, there is a ton of other stuff they are doing to stay healthy that you are not measuring, making it harder to say “hey, it’s the running that did it”.

On the interval training side of the fence, Elissa Epel released a study that suggested interval type training was really beneficial and associated with longer telomeres. A few problems with that study: the participants averaged 63 years of age, were osteoporotic and self-evaluated their exercise intensity. Nevertheless, there was a clear cut non-chance association with longer telomeres.

Finally, the best ones, in my book, is the “Danish Twin Studies”  Mech Ageing Dev. 2011 Nov-Dec;132(11-12):568-72. Leukocyte telomere length and physical ability among Danish twins age 70+.

Bendix L, Gade MM, Staun PW, Kimura M, Jeune B, Hjelmborg JV, Aviv A, Christensen K.

And

Am J Epidemiol. 2008 Apr 1;167(7):799-806. Epub 2008 Feb 12.

Telomere length and mortality: a study of leukocytes in elderly Danish twins.

Kimura M, Hjelmborg JV, Gardner JP, Bathum L, Brimacombe M, Lu X, Christiansen L, Vaupel JW, Aviv A, Christensen K.

Source

Center of Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

The first study looked at both fraternal twins, who are not genetically identical and monozygotic (identical) twins, where genetic variation is not a factor and at least early age environmental issues (basically epigenetics), were the same. They found the fitter member of the pairs had significantly longer telomeres.  The next study correlated telomere length with mortality, in a similar population. They found the twin with the longer telomeres was longer lived and the more the difference between the two, the more predictive telomere length and life/death were.

I wish the same group would have done both studies and in all of the above studies there are measurement issues. I wish they would redo everything with the Life Length assay, which would be far more accurate and instructive.

So, there is data.  It is just not as strong as we’d like it to be. In our book The Immortality Edge, we recommend interval training in a non-joint damaging way, as the best for people who are just beginning to exercise. For the rest of us, moderation in training load that does not overload the body’s oxidative defenses and does not damage the joints, appears best. Note this does not exclude high intensity exercise. It just puts it in the context of overall training load. We did not discuss the signs and symptoms of overtraining in the book, but you can find them anywhere on the internet. If you want to go hard, find the level where you start to become over trained and back off. As your training tolerance builds, you can push again, looking for the same parameters. If you hit a plateau and can get no more fit than you are at that point, reassess your training methods and programs. It’s rare that an uncoached athlete comes close to their genetic potential, which would be the other reason you plateau.

Personally, I do my highest intensity work in the deep water with a vest – I no longer sprint at the track. I also use an Airdyne and a Versa Climber, both of which are very low or no impact.  As far as strength, I favor body weight stuff and my good friend Eddie Baran is the guy you want to see for that:   http://gymnasticabs.com/

Best,

Dr Dave

The sad failure of calorie restriction

I can’t say it’s a surprise that calorie restriction has failed to extend life in higher primates.  It was at least successful in flies, worms and some lower mammals.  I understand it has not led to mass gorging on the part of the CR society, who bravely soldier on in the face of this recent finding, perhaps refusing to believe it, or maybe just having too much invested to quit now.

CR, as a way of life, is no picnic. If you have seen some of these people, they are thin to the point of emaciated. Clearly, it takes a determined and brave person to fight one of the most basic urges – the one to eat. I believe the current plan is for the CR society to look at their data around 2030 to 2050.

You have to hand it to them. They are in truth doing the world’s only attempted human longevity study, where people are actually followed into their old age and death over several decades.  When people say things to me like, “Well, TA-65 is not proven to extend life!”,  I say “You are right! Nothing is, because no one has ever done a study that goes out long enough to prove that point.”  The CR society may be the very first to do this and win, lose or draw, on this one I have to say they have some serious guts.

Especially in the face of what has to be a very basic mistake on the part of people researching this. In case you missed it, the big glitch was that the longer lived monkeys were actually fed a much healthier and more controlled diet than the shorter lived ones, who were given the equivalent of McDonald’s every day, in monkey terms.  I think there is enough human data to prove that would kill people off early, too.

Still, there is a lot we have gained from these experiments and much more to learn.

We now understand the interaction of some “metabolic stress handlers” like mTOR, FOXO and the sirtuins. We know they build up the antioxidant defenses of the body to a greater degree than an ad libitum diet, and we know that they help manage insulin and glucose in the process. Such knowledge could come in very handy when developing new treatments for diabetes. We also know these metabolic stress handlers help control the expression of telomerase, the enzyme that lengthens telomeres. It won’t be long before we know how telomeres control the expression of these proteins in reverse, so to speak.

All of this helps us understand the aging process better and develop new strategies to combat disease, suffering and aging as a whole.

So it’s time for a prediction. When the CR society data is finally in, I think we will see that they are dying far less of stroke and heart disease complications, and far more of immune dysfunction and cancer.

Unless of course, they remember to take their fish oil and TA-65!

Brave souls, I commend you and wish you well!

Doc

How do telomeres protect the ends of the chromosome?

Telomeres protect the genetic information by multiple methods. First, as cited below, DNA polymerase cannot replicate the ends of the chromosome. DNA polymerase is actually “too large” to stay on the single-stranded overhang of DNA that is left and literally falls off the end of the chromosome. There are biochemical and electromagnetic reasons it separates.  When it leaves the chromosome end, it has not completed replication of that portion of the DNA.  An unreplicated DNA end is considered “uncapped” which would turn on the “DNA damage response” and cause the cell to commit suicide – known as apoptosis. The telomeric segment of the chromosome is the “end cap”, since it falls back over in itself and never allows the repair and damage pathways to see an “uncapped” DNA strand. To the damaged pathways, it looks like a complete double-stranded end of fully replicated DNA.

The second known way it protects: The uncapped ends of a DNA strand are subject to recombination with other uncapped DNA strands, causing genetic aberrations and instabilities that may lead to mutations.  This actually does happen when the telomeric segment becomes too short. Some cancers use this method to lengthen their chromosomes and avoid the DNA damage response, which would otherwise kill the cancer cell.

A common mistake I see in answering this question: telomeres do not contain “genes” or any genetic material in the classical sense at all. They consist of six different deoxynucleic acid molecules in repeating sequence, which does not code for anything so far as we know at this moment.

The next mistake I see and hear often is that certain products lengthen telomeres. Only TA-65 has any human data and has a completed human trial reported in Rejuvenation Research. The data from the second part of that trail is due for release shortly and is very positive. With regards to ANY other product as of this writing: that is not true in humans because no other products have completed any human trials. One product has one source for laboratory data that, when repeated by another lab, gave two different results. The first repeated result was negative for telomerase activation and the second was weakly positive compared to TA-65, but again, these were lab trials, not human. I do not know if that information will be published yet.

The information about telomeres/telomerase and telomerase activators and inhibitors is always growing and sometimes changing so, in a year, some of what has been said above may no longer be accurate; but as of today it is.

The problem with freedom of speech

We have an election coming up and I am all for freedom, but in response to an article sent to me for evaluation on a widely read internet site, I wrote the piece below. The central theme of the article was, just because there were two well-publicized “fish oil no good for your heart” reports this year, fish is still good for you, because it’s food not a supplement.

I wish people who write about health matters on the internet would learn to read studies and do a tiny, tiny little bit of research on the internet itself, before writing misinformation. After thousands of studies have shown that fish oil supplements are at least as beneficial as eating fish and do not contain mercury, you once again advance the ridiculous concept that there is something magical in fish that is not found in fish oil. The active ingredient is, was and always will be Omega 3 fatty acids, in both fish and fish oil, when it comes to disease prevention.

Next, instead of placing all the weight on one or two studies, it would make more sense to look at the big picture and comment on that. There are thousands of positive studies on fish oil. This one was NOT A STUDY. It was a meta analysis, a tool used to generate quick inexpensive publications that are totally dependent on data input. The data used in this one went back to 1987, long before any of the highly purified ethyl ester fish oils were available and no attempts were made to assure its validity, other than “looking at the study”. Next, there was no attempt to control, for some of the most important confounding variables, like the increasing use of cardiovascular meds. Next, no attempt was made at measuring the Omega 6/3 ratios, to establish effective treatment levels – the usual dose was “one a day”. These last two comments also apply to the Origin-Grace study, which was NOT a fish oil study by design. It was used to study Glargine (lantus) insulin efficacy in diabetics and was funded by Sanofi, the makers of said insulin. The fish oil group was a sub group analysis. The results of fish oil’s “failure” (actually, it was reported as having no effect) were released as giant headlines, weeks before a tiny headline, noting the failure of Lantus to prevent progression of heart disease. In this study, over 50% of the participants were also on statins, aspirin and other anti-diabetic drugs. No attempt was made to look at the role these drugs might have played in the progression of heart disease or the interference with insulin or fish oil. The rash of the “Fish oil no good for your heart” clearly defrayed the public and physician (!) attention away from the failure of Lantus insulin.

This Emax piece, sent to me, is just another in a long line of “articles” that simply make conclusions based on parroting back misinformation. I know it takes a little time to actually read a study, learn about what it really says and you might miss the window of public interest on the internet (God forbid), but you might actually have something valuable to add to reality.

This is the similar logic that goes on when people write that telomerase causes cancer. Several years ago, one of the Nobel Laureates raised the theoretical concern and now it is gospel truth, with no one bothering to look at all the research and growth in knowledge that answers that concern definitively.

This is the same stuff when people write to me about the “work” done by an electrical engineer who was convicted of deception, in Texas surrounding supplements he was selling: Brian Peskin. http://www.quackwatch.com/11Ind/Peskin/complaint.html

This individual has used his “professorship” status to garner the term “doctor” and make statements about your health, particularly regarding dangerous effects of Omega 3’s. Classic example.

This is the problem with the internet. There is no mechanism to check the validity of who and what is being said, other than the reader doing a little extra research. If it is advertised well enough, it becomes “truth” until someone finds out the real truth and disabuses people of their misconceptions. Sadly, this process takes an extra 30 seconds and no one does it. It would take another 30 seconds, to actually read the study, instead of just reflexively responding to the headline. That tallies up to be about 1 minute no one can spare.

I guess it is only going to get worse. I had a “discussion” with my friend’s 12 year old daughter a month or so ago, about why no one uses email any more. “It’s too slow!!” she said, emphatically. So, we had a race – her text vs. my email. She won, beating me by 17 seconds. I had to ask myself what is so friggin’ important, in the life of a 12 year old, that 17 seconds has become too long to wait. And here I am expecting adults to do a minute’s worth of work.

Freedom of speech was designed to protect the rights of individuals, to express different and dissenting opinions. The key word is “opinion”. Spreading scientific misinformation about factual events has another name. It’s called BS. Of course if there were a law to protect us from that, we would have no internet and probably no government either!

TA-65 causes cancer

No, it does not! That is the short answer. The rest of it requires me to get all sciency on you, so read on at your own risk!

Recently, I read yet another brilliant rocket scientist, stating that telomerase is turned off in most of our cells to protect us from cancer. The implication is, of course, that turning it on will increase your cancer risk, which would make TA-65 a cancer causing agent. The author then went on to cite some erudite scientific opinions in articles that were 2 and 6 years old respectively.

In this field, even when one is quoting Nobel Laureates, research that is 6 months old, is old news and over a year, is the dark ages, unless it has been recently repeated and updated.

The link between cancer and telomerase is embedded deeply in previous theory, but not actual fact.

The simple fact that 85% of human cancers appear to massively over express telomerase has been misinterpreted as proof that telomere shortening has something to do with protecting us from cancer and that telomerase is oncogenic.  Short telomeres are definitively associated with cancer, not the other way around.  If the cell regulatory mechanisms are intact, short telomeres (usually less than 5KB) will turn on cellular senescence mechanisms, or if they are “allowed” to grow shorter, apoptosis follows. Both mechanisms are mediated through the mitochondria and p53 – but telomeres “rule” this process. If the cell undertakes, for whatever reason, to undergo the minimum of 4 “escape” steps to become cancerous, it may induce the very last step of telomerase over expression, which will effectively make the cancer cell line “immortal”. But telomerase is not the inciting factor any more than anaerobic metabolism, angiogenesis or Matrix Metalloproteinases are the causes of cancer and its subsequent spread. The disease, that is cancer, induces all these changes – and any attempts to fix them, without fixing the underlying causes, will not fix the cancer. This is why Ozone/oxygen therapy will not cure cancer. Cancer chooses to live in an anaerobic acidic environment and induces all kinds of things to make that possible. Dumping in oxygen or oxygen free radicals will not damage the cancer. It will simply wash those compounds away with its overdeveloped vascular system (the result of inducing angiogenesis using vascular stem cells) the way it washes away the toxins of its explosive growth and metabolism.  Blocking telomerase will not cure it either.  The recent abject failure of telomerase inhibitors (like Imetelstat), cited in one of the answers as a potential cure for cancer, shows the flaw in this theory and this logic. Indeed, telomerase inhibition leads to only temporary suppression of cancer and then massive aggressive and treatment-resistant rebound, as the cancer “figures out a way around telomerase inhibition”.  It is too early to say what will happen with the PinX mimics.  It is possible that temporary suppression of tumors may be enhanced by telomerase inhibition via concomitant increased sensitivity to chemotherapeutic agents.  In chemo-responsive tumors (without telomerase inhibition) however, telomere lengthening and a decrease in the variability of mean telomere length are positive signs, again pointing to some restoration of genomic stability. Aggressive malignancies replicate so rapidly, their telomere length remains short and the distribution of actual telomere lengths is very wide, within that parameter (e.g. short, very short and almost immeasurably short!)

But, once again, 15% of cancers do not rely on telomerase to lengthen their telomeres, but use the ALT mechanism instead, so telomerase expression is not a prerequisite for cancer either.

Early studies that used known oncogenic viruses to insert telomerase genes into the mouse genome in tert+/- and tert-/- mice are most likely the cause of the persistent misconception that telomerase is oncogenic and that turning it on will somehow foster cancer.  When non-oncogenic strains are used, there is no increase in cancer and there is increase in life span and health span of the animals (see any of the recent studies by Maria Blasco). In humans, the mild telomerase activator, TA-65, initially an anti-HIV compound, has shown no increase in cancer (since 2005- Geron data, http://www.ncbi.nlm.nih.gov/pubmed/21426483,   http://www.ncbi.nlm.nih.gov/pubmed/20822369), nor has it led to increased mortality in cancer patients either; and new human trials are due in the next 1-2 years. Finally, if telomerase were oncogenic, our species would not survive, since both stem cells and germ cells require “excess” telomerase expression to remain viable.

Cancer may use telomerase to stabilize its fragile genome and prevent its own destruction through genetic instability and reproductive failure, but telomerase does not cause cancer.  Cancer causes over expression of telomerase, as it causes aberrations and over expression of many other enzymes.

I should point out a few things:  The person asking the question states that “new drugs” have been developed, that lengthen telomeres. I am only aware of TA-65 as having human studies and it is a supplement, not a drug. Other supplements are being investigated and I am sure someone is working furiously on a drug somewhere, given the potential revenue it might generate.  The Israeli’s reportedly are working on a telomerase activating drug for very specific use (not anti-aging), but it is not out of Stage 2 trials, as of yet.

My personal theory on why the telomerase gene is present, but inactivated in somatic cells, is the protection of evolutionary pressure on the species. During our past, there were not many of us and we were ill-equipped to capitalize on what has to have been even more enormous resources than we have now. Survival of the fittest dictated a rapid high pressure rise and demise of useful and unuseful traits, both genetic (slow and cumbersome) and epigenetic (far more rapid and “reflexive”). If people lived extremely long healthy lives, they would be better equipped to preserve their own static genomes and, unless they were able to reproduce much longer than we now do, some parts of their epigenomes as well. They would also have the experience and power to outcompete the young. So, simply put, telomerase suppression could exist simply to guarantee room and resources for the young of the species and to ensure evolutionary pressure remains meaningful.  Since genetic engineering is likely to be a reality in the next decade, we will gain a measure of control over evolutionary pressure, as well as health and longevity, since they are all interrelated.

I fully admit this is just a theory, but when one looks at the evidence, it is certainly as viable as “to protect us from cancer”. If we look at current cancer rates, it’s not doing a very good job and it was unnecessary during all but our most recent existence, since we didn’t live past 50, on average, until a century ago, when the age-related disease we call cancer was not nearly as common as a cause of death. This would make the “to protect us from cancer” role of telomerase suppression a very recent evolutionary acquisition!

The ramifications of lengthening human life span and health span are many and can be summed up in this simple statement; we are stone aged genes in a space aged time. Meaning, people will remain subject to all the behavioral programming and perceived competition for resources that have plagued mankind since its inception. But, it also represents a tremendous opportunity to grow beyond and transcend those behaviors. It will certainly be interesting and could very well happen, on at least a small scale, in the lifetimes of many of the people reading this, thanks to the efforts of some of the aforementioned scientists.

Dr Dave

Should you take resveratrol?

For the past decade and a half at least a billion dollars in research marketing and publicity money was spent trying to find a home for a class of epigenetic molecules (histone deacetylases) known as sirtuins.

If this sentence has your finger hovering over the mouse, ready to move onto something more interesting and familiar, HANG ON!  At least let me set up a little back ground for you.

A fellow by the name of Sinclair became pretty famous for his research into longevity by researching a molecule initially found in red wine grapes.  That molecule was known as Resveratrol. Subsequently, after a lot of typical internet finagling, the molecule became known as a fountain of youth, a telomerase activator, a telomerase inhibitor and all kinds of other confusing and wonderful things that led to at least a few hundred million dollars for various vitamin gurus and vitamin companies.

And for a long time, the claim was made that Resveratrol modified the all-important class of molecules, known as sirtuins. It was supposed to be a “sirtuin activator”.  More than one famous guru and a lot of famous supplement companies and vitamin foundations touted this as a fountain of youth.

Even the good Dr Oz got into the act, although no one is 100% sure if it was willing participation, or not.  Dr Sinclair did OK, too. He sold Sirtris Pharmaceuticals to Big Pharma giant GLaxo Smith Kline (GSK) for $750 million, one of the biggest dollar amounts for a small bio medical firm ever paid.  Soon after, some of the Sirtris execs raised some eyebrows when they (now working for GSK) started selling Resveratrol online.

Sadly for Resveratrol fans, GSK had to halt the trials on the “super” Resveratrol, developed by Sirtris, because of human toxicity and lack of efficacy. In addition, most of the findings associated with Resveratrol could not be replicated.  OOOPS!  There goes 750 million.

If you’ve ever wondered why Big Pharma has been so slow to jump on the anti-aging bandwagon and develop the magic pill they so desperately want, this is no small part of the reason. It parallels the multi-billion dollar failures, fraught with lawsuits and human harm that have occurred as a result of Big Pharma’s failures to develop effective weight loss drugs.

Damn! The basics of human behavior and human existence are so friggin’ complicated!

Hint: now that we are beginning to piece together the epigenome and the role of epigenetics in all cellular functions, the day is coming when both magic pills will become available.  Heck, we already have TA-65!

Historically, the link between research and eventual true human longevity will go straight through TA-65. Not so, with Resveratrol.

Now, all is not lost for Resveratrol.  It turns out it’s a good antioxidant and a modifier of some important molecules, known as “adipokines”, which help the body manage energy, glucose, fat and stress – all important stuff.  This cannot help but influence telomere health, at least indirectly. But as I proved to myself and at least a few people who would listen (along with some help from super scientist Bill Andrews of Sierra Sciences), Resveratrol is neither telomerase activator nor inhibitor.

OK, now let’s back up to the molecules that started all this – sirtuins.  I predicted a bunch of things, when I wrote my portion of The Immortality Edge and the many newsletters that have followed since then. One of them was that calorie restriction would be a totally impractical way to extend life, and the other was that telomeres and sirtuins would be linked.  I said that I thought telomeres would eventually be shown to influence the activity and expression of sirtuins.

While that last thing has not yet come true, its corollary has.  Sirtuins have begun to be shown to influence telomere length.

There are seven or eight specific sirtuins for humans that we know of.  So it’s time for another prediction!

I predict the sirtuins will turn out to be like the Chakras – an energy centered concept that features in tantric and yogic traditions of Hinduism and Buddhism.

We started out hearing about seven or eight and now there are at least 21!  I am willing to predict we’ll wind up with at least 21 sirtuins, when it’s all said and done, and no, I am not implying the two concepts are linked.  Or am I!?

Anyway, the most studied sirtuin is SIR 1.  Most studies have shown that this protein only confers stress resistance and improved health in the face of stress itself. Then again, who among you eats perfectly, sleeps perfectly and lives a stress-free life!  We don’t even know what those things mean for most people.  Again, as epigenetics evolves and allows the study of individual metabolomics (how each of us processes everything!), we will have an answer and it is not likely to be the same for all of us by a long shot!!! But the sirtuins will be a big part of it and of course, so will your telomeres!

The problem with the sirtuins as longevity molecules is that up until now, SIR 1 the most studied of them, did not confer longevity. SIR6 however, may in humans. Notice I said “up until now”. A recent study (see below) suggests that there are genetic variants, that do indeed make a population of people stand out for their longevity.  Now the study has some shaky/shady assumptions and statistical play.  But it is still intriguing and needs further study, of course.

I would like to suggest, to the authors, that they reverse the direction of their study and see what role telomere length has on the expression of the sirtuins, specifically SIR1 and 6.  Then I think we will really get somewhere.

It won’t get GSK their $750 million back, nor will it restore Resveratrol to its (funnily continued!) much vaunted status as a longevity drug.  But it will get us closer, in a meaningful way, to solving what I think is the disease called aging.

In my next life, I want to come back as a basic science researcher.  Then again, if I live long enough, I could go back and swap my MD for a PhD and have a ball.

Anything is possible, so don’t give up – and take your fish oil, TA-65 and if you must, your Resveratrol.

Biogerontology. 2012 Apr;13(2):119-31. Epub 2011 Oct 5.

Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity.

Kim S, Bi X, Czarny-Ratajczak M, Dai J, Welsh DA, Myers L, Welsch MA, Cherry KE, Arnold J, Poon LW, Jazwinski SM.

When birds of a feather flock separately

Identical twins have always been the subject of much study.  Since they are genetically identical, much has been made of their proving or disproving the nature versus nurture argument. If you missed that one, it goes like this:  Are your genes (nature) the most powerful determinants of your future, or is your environment (nurture) the most important thing.

The emerging science of epigenetics has shown us that, for the average person, with average genes, at least 70% and perhaps as much as 80% of what happens in terms of health span and life span is epigenetic and thus, in most cases, subject to environmental causes.  Complicating matters somewhat is the fact that epigenetics are also ‘heritable’, meaning you get much of your epigenome from your parents as well. The good or bad news with that is that you can influence even inherited epigenetics, to a large degree.

I’ll get back to identical twins in a second, but I want you to understand a few things.

First, you are not beholden to your parents’ fate.  A good friend of mine and a doctor and I had a friendly argument the other day.  Jack, I will call him, lost his dad to a massive heart attack at age 46, from a specific lesion of the coronary arteries, known as left main disease.  Jack himself started with chest pain in his early 40′s and was diagnosed with, you guessed it: left main disease. His cardiologist told him this was very likely heritable, e.g. a genetic trait.  No attention was paid to the fact that Jack lived under his father’s roof for 25 years, ate the same things and had exposure to the same stresses and more, since he became a doctor. Undoubtedly he was sleep deprived and still has no idea what his Omega 6 to Omega 3 “fish oil” levels are.

While it is true that Jack may have a genetic predisposition and a specific “allele” (a form of a gene that can exist in several different forms and confer several different risks or lower risks) for left main lesions, it is also likely that, that allele is expressing itself in spades because of the environmental factors and epigenetics results of those factors.

Which brings me back to identical twins. Recent studies in brain development of identical twins, with regards to both autism and schizophrenia, suggest that there are major differences in brain development that depend on the environment in the womb and the placental development and flow to each twin. In other words, the healthier twin usually correlates directly with more, or more balanced nutrients and more normal birth weight. Now understand, I am taking a very complex topic and simplifying it greatly for you, but a couple of key concepts come out here.

First, identical twins do not always have an identical intrauterine environment. They may get different nutrients, different amounts of calories, different maternal hormones or growth factors, different temperatures and toxins, etc., etc.  If you are saying “Duh” right now, then please remember that placental/intrauterine medicine is still in its infancy – no pun intended.  These studies alone should stimulate much more interest and hopefully research dollars, to investigate the effects of the intrauterine environment.

Second, these effects during the pre-natal period have far reaching effects that may not show up for years, or even decades. Hence, the explanation why kids of moms who took Omega 3′s and who had higher Omega 3 intake during their own first five years of development turned out to have better hand-eye coordination and scholastic performance in their adolescent years!  There are probably many more examples of nutrient-based advantages kids have when their moms eat healthy, but you can understand why that one is among my favorites.

Third, this kind of epigenetic “manipulation” may not be fixable in the adult stage, as it may permanently alter gene expression. In other words, autistic and schizophrenic children are not likely to become fully functioning adults, at least in the more severe cases. The good news is that in milder cases, huge amounts of progress can be made.

So too, it is with my friend Jack and his heart disease.  So too, it is with you and whatever maladies or ghosts of your parental genetic past you may be facing.

For the majority of us, epigentics means we are responsible.  So remember that the next time you reach for a donut!

Doc

Is Spinach the New Broccoli?

I have written a lot about broccoli and its related Brassica family. Broccoli has long held true “Super Food” status. Unlike some other highly touted foods, it actually has a fairly balanced ratio of omega 6 to omega 3 fatty acids (although it is extremely low in both) and contains Sulforaphane and Indole 3 Carbinol.

Thanks to the emerging study of how food affects our epigenetics, we know, right down to a sub cellular level, how nutrients like this fight cancer and promote health.

Well, now, thanks to the same type of studies, it has been found that high nitrate foods (not to be confused with nitrite, which is cured meats!) can actually promote muscle strength and health.

It turns out, Popeye may have been right after all: Spinach really may increase your muscle strength. Other high nitrate vegetables include chard, beet root, and certain types of lettuce.

How much do you need? Scientists found that 200 to 300 grams of spinach (about 10 ounces a  day) or 3 beet roots would do the trick. The mechanisms, by which spinach increases strength, seem to have to do with protein synthesis and calcium metabolism by muscle.

What I find particularly cool and interesting is that you can add this to your broccoli consumption for completely different effects from each vegetable. So, we know that at least these two seem to have serious health and anti-aging benefits.

As more and more foods are studied from the epigenetic standpoint, I am certain a lot of myths will be debunked and a lot of old wives’ tales proven true!

Stay tuned and I will keep you posted on foods, supplements, behaviors and lifestyle habits you need to know about to stay as young as possible.

Dr Dave

Why not resveratrol?

I got an interesting question from a reader who wanted to know why “resveratrol” was not mentioned in our book, The Immortality Edge.  Given all the hype that resveratrol continues to get, it’s a fair question. But in that last sentence is the answer, “hype”.  I can remember someone writing in and saying her doctor told her to pick either TA-65 or resveratrol, because one was a telomerase activator and the other (resveratrol) an inhibitor and they should not be taken together, because they counteract each other.  She stopped the TA-65 (no, not because of cost), because she could not imagine life without resveratrol. This is not the first time I have seen or heard of absolute devotion to resveratrol.  Frankly, this kind of almost religious ardor, over a supplement, should be reserved for something that has actually panned out and been proven – like fish oil!

Resveratrol made its reputation based on the “fact” that it activated a class of histone deacetylases (that there, is one of them epigenetic type terms) known as “sirtuins”. Sirtuins were thought to be longevity molecules, for a long time, before cracks in that argument began to appear. Hundreds of millions of dollars were spent on resveratrol research and sirtuin research, in the hopes of finding the “secret molecule of longevity”. As always happens in today’s world, rumors started and the internet bred more and viola; you now have the wonder drug resveratrol, key to the sirtuins, gateway to the same benefits of calorie restriction for longevity…

Now for a little reality check.

Let’s start with the biggest bomb first. Glaxo Smith Kline, a pharmaceutical giant, paid $720 million to aquire Sirtris Pharmaceuticals, a company headed by Harvard resveratrol guru, David Sinclair. While it is not 100% clear what happened afterward, rumor has it, that much of the data provided prior to the sale, including that on resveratrol and its more potent synthetic analogs, could not be reproduced by GSK’s scientists. Then the actual resveratrol-derived compound, that was in clinical trials, caused several cases of kidney failure and that was the end of “resveratrol as a drug”. That, we do know for sure – no rumors.

Next, it was found that resveratrol probably does not directly interact with sirtuins at all, but works via a different class of energy sensors called “adipokines”, making it a metabolic shepherd, not a longevity one; although fixing a sick metabolism might indeed boost longevity, at least to a more normal level than dying prematurely!  This association with an entirely different class of molecules broke the knee jerk association of resveratrol with sirtuins. Or at least it should have! There are still a ton of folks out there, who didn’t get the message and continue to publish outdated and incorrect information about resveratrol and sirtuins.

Next, the whole sirtuin deal came into question. The longevity gains shown with sirtuins were shown to occur only in metabolically stressed animals, not normal healthy ones. Finally, it was recognized, that people who express dramatically higher amounts of sirtuins, because of a genetic aberration, do not live longer than “normal” people. Fortunately, they don’t die younger either. But sirtuins seem to work only when the organism is under stress.  Guess what. Aging is stress. Diabetes is stress. Obesity is stress, so sirtuins remain attractive candidates for intervention into the diseases of aging and improving health span, if not life span. Sooner or later, Big Pharma will have its sirtuin activator.

Now our book, The Immortality Edge, is the first and only book of its kind about telomeres. Resveratrol has been touted as both a telomerase activator and telomerase inhibitor. How can it be both? Well, technically speaking, there is similar information concerning fish oil (Undarti Das et al.). It is possible for compounds to act one way on cancer cells and another on aging or regular “healthy cells”, that are non-cancerous. So far so good, right – I should have put resveratrol in the book. Well, I did a little research on my own, with my friend Dr Bill Andrews, who tests for telomerase activity like no one else! I sent in several samples of resveratrol, from different well-known reputable manufacturers and not one of them had any effect on telomerase, at all.  I believe Bill has tested other samples as well and has NEVER found one iota of telomerase activation from anyone’s resveratrol. In addition, there is a guy out there who purports himself as a “student of longevity”. He had a web site and was selling potential “telomerase activators” and his own brand of resveratrol. This guy was and is very popular and has a forum that many people visit and pontificate in all manners about longevity. His particular brand of resveratrol was toxic to human cells at relatively low concentrations and his telomerase activators didn’t activate squat. Now he sells TA-65, which does work on telomerase, so he finally got it right!

So, is resveratrol toxic? Is it worthless? Generally the answers would be no and no, if you get a reputable brand. But, in spite of the occasional article that comes out claiming it’s a telomerase activator, we could never demonstrate that with commercial brands, nor has there ever been any human testing outside of cultures in a dish. Because of its interaction with adipokines, resveratrol does indeed seem to have some important metabolic benefits, especially if you are fat or diabetic. It may help you be healthier, which is a huge thing. But, it probably won’t help you live longer. I should also mention that, as a plant-based polyphenol, it is a potent antioxidant and I used it long before it was popular, in a sadly now defunct supplement a few of you will remember as Super Wrinkle Guard. So, I am not “anti-resveratrol”. I am simply interested in facts.

The compound we chose in The Immortality Edge is far less known, but at least as interesting to me as resveratrol and its cousin pterostilbene. Instead of coming from red wine, like resveratrol, we chose the polyphenolic extract of the aronia melanocarpa berry, which has the highest polyphenol content, anthocyanins, flavonols and cinnamic acids of all of the berry families, including the much vaunted blueberry! Aronia is not a telomerase activator or a longevity inducer either, but when it is finally studied, it will be found to be more potent in most aspects than resveratrol.

That said, if you like resveratrol and want to keep taking it, do so by all means. Just don’t expect it to function like TA-65.

Doc

Cancer and other bad genes

Did you ever wonder why we have “bad genes”.  I mean, think of it.  If our genetics is supposed to help us survive, why are there such things as bad genes, and more importantly, why do they persist?  If you believe in natural selection and evolution, then only the best of the gene pool should survive and reproduce and this should be mirrored in the survival of the species.

Why should we have oncogenes (genes that code for cancer) that need tumor suppressor genes to fight them?  Why should we have genes for early heart disease, Alzheimer’s and so forth?  Now, I can hear the more scientifically educated among you saying, “SNPS” (pronounced snips). Single nucleotide (DNA) point substitutions are among the more common mutations that cause bad things.  Sometimes, they are clustered in families and sometimes they just seem to happen in the same areas more or less randomly, causing early disease or death.  It seems that certain areas of our DNA are more susceptible to oxidative (free radical) damage than others and are more common areas for SNPS. But this type of mutation is relatively rare compared to more complicated “allelic” variation.  Different “alleles” (these are considered non-mutated “normal” variants, because they make functional proteins) for certain key protein products are the most common form of “bad genes” by far, and are the most common cause of true genetic problems for a fair number of people.

One in particular known as “APOE4” is associated with a 4-fold increase in heart disease, stroke and Alzheimer’s.  So why is this allele still around?

The simple answer is we are stone aged genes in a space age time.  The APOE4 allele is actually the true “human” gene form that can be traced back several million years, to our ape ancestors. It seems to confer resistance to hepatitis and other viral illnesses and allows its holder to reach reproductive age and beyond – something that is the basis of all of our genes.  I have said before that after age 40 Mother Nature doesn’t really care pro or con about you.  Just live long enough to reproduce and rear your young and you’ve made Mother Nature and Darwin happy!  So, something that knocks you off between 40 and 50 does not threaten the overall survival of the species!

Interestingly, the mutated APO alleles, that most of us carry (E2 and E3) are something we acquired later in our evolution. These genes do not code for bad things at an early age, so that allowed us to do two big things that ultimately improved our survival over our ancestors: live longer and eat meat and handle the end glycosylation products associated with cooking*!

Now here is the kicker!  Statistically, far more people will be victims of epigenetics than genetics.  In other words, most of us were dealt a pretty good genetic hand and we’ll mess it up with poor diet, sedentary behavior, stress and lack of sleep compounded by things that shorten our telomeres, lower our vitamin D levels and let inflammation run unchecked, because of low Omega 3 fat intake and excess Omega 6 and saturated fat intake.

The uncovering of our “bad genes” is far more often epigenetically mediated, than genetically mediated. We have control over far more of it than was ever realized before. So, while Mother Nature and Darwin may only care if you make it to 45, you and I have much bigger aspirations!

So, take your fish oil, eat well, sleep enough and get off your arse and move!

Doc

*Yeah I know I opened up a can of worms with this statement. Isn’t cooking food bad and doesn’t it caramelize things, making them “sugary”? Well for now you’ll have to settle for the short answer: yes, it does, but it matters far less than other sources of carbs and sugar. More on that later if anyone is interested!