Vitamins, supplements and telomerase – upregulation or downregulation?

It seems like scarcely a day goes by now without new telomerase research news items showing up in the popular press, the latest having to do with fish oil.  I mention this news here but my purpose is to make a few broader points:

1.      Taking a number of popular supplements in the anti-aging firewalls Supplement Regimen like Vitamin E, fish oils, Vitamin D3 and resveratrol can lead to telomeres being longer than they otherwise might be, possibly because they induce the production of telomerase, possibly for other reasons.  As such, these supplements are quite possibly life-extending.

2.     Despite the popular conception, telomere lengths do not uniformly get shorter with advancing age.  Sometimes they get longer over substantial periods of time.  Nobody is quite sure of how or why.

3.     Many of the same supplements that lead to longer telomeres in healthy people seem to have the capacity to turn off telomerase and shorten telomeres in cancer cells and help kill them.

Fish Oil and longer telomeres

Yesterday’s news is based on a January 20 publication in JAMA: Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease.  Context  Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood.Objective  To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age.Design, Setting, and Participants  Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years).Main Outcome Measures  We measured leukocyte telomere length at baseline and again after 5 years of follow-up. — Results  Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P < .001 for linear trend across quartiles). –. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98).Conclusion  Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.”

The temptation is to conclude that “taking fish oils leads to less telomere length shortening,” but that is not what the study says.  The conclusions of this study are based on levels of DHA and EPA measured at baseline and do not take possible supplementation during the study period into account.  Further, the study population was a very special one, people with coronary artery disease.  Another temptation is to conclude that fish oil leads to the expression of telomerase, but this conclusion is also not directly supported.  The study does not say why the rate of telomere shortening was less in those with higher baseline levels of the fish oils.  Nontheless, the popular press has yielded to these temptations with news story titles like Is Fish Oil the Elixir of Life? And  Stay young by eating fish oil, say scientists. I chalk this up to a general hunger in the population for anti-aging news.  And now, after Blackburn, Greider and Szostak  have received a Nobel prize for work on telomeres and telomerase, it is almost household news that longer telomeres are associated with longevity and are better for health.

Natural telomere lengthening with age

The report on omega-3 fish oils and telomeres was preceded two weeks ago by another PLoS ONE report based on data for the same 608 individuals in the Heart and Soul Study Telomere length trajectory and its determinants in persons with coronary artery disease: longitudinal findings from the heart and soul study.  METHODOLOGY/PRINCIPAL FINDINGS: In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p<0.001). Three distinct telomere trajectories were observed: shortening in 45%, maintenance in 32%, and lengthening in 23% of participants. The most powerful predictor of telomere shortening was baseline telomere length (OR per SD increase = 7.6; 95% CI 5.5, 10.6). Other independent predictors of telomere shortening were age (OR per 10 years = 1.6; 95% CI 1.3, 2.1), male sex (OR = 2.4; 95% CI 1.3, 4.7), and waist-to-hip ratio (OR per 0.1 increase = 1.4; 95% CI 1.0, 2.0). CONCLUSIONS/SIGNIFICANCE: Leukocyte telomere length may increase as well as decrease in persons with coronary artery disease. Telomere length trajectory is powerfully influenced by baseline telomere length, possibly suggesting negative feedback regulation. Age, male sex, and abdominal obesity independently predict telomere shortening.”

Note that this is not the first study to show average telomere length increasing for a substantial part of the study population over a substantial period of time. According to a large Swedish study, a third of the population experienced telomere lengthening over 9 to 11 year intervals(ref).

Fish Oil, other supplements and turning off telomerase in cancers

According to the 2005 report Polyunsaturated fatty acids inhibit telomerase activity in DLD-1 human colorectal adenocarcinoma cells: a dual mechanism approachWe investigated the inhibitory effect of various fatty acids on telomerase, with particular emphasis on those with antitumor properties, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).  – In contrast, cis-unsaturated fatty acids significantly inhibited the enzyme, and the inhibitory potency was elevated with an increase in the number of double bonds. Accordingly, polyunsaturated fatty acids (PUFAs), like EPA and DHA, appeared to be powerful telomerase inhibitors. — Culturing DLD-1 cells with either EPA or DHA resulted in a remarkable decrease in telomerase activity. EPA and DHA inhibited telomerase by down-regulating human telomerase reverse transcriptase (hTERT) and c-myc expression via protein kinase C inhibition. These results indicate that PUFAs can directly inhibit the enzymatic activity of telomerase as well as modulate the telomerase at the transcriptional level.” 

So there we have it.  The same DHA and EPA fish oils that seem to be correlated with longer telomeres in the recent population study also clobber telomerase in a cancer cell line.  This property seems to be shared by several other popular supplements as well. 

Alpha-tocopherol (Vitamin E) seems to repress age-related telomere shortening(ref). Yet, the 2007 study Vitamin E suppresses telomerase activity in ovarian cancer cells concludes “Our data suggest that, by suppressing telomerase activity, Vitamin E may be an important protective agent against ovarian cancer cell growth as well as a potentially effective therapeutic adjuvant.”  

Another supplement that is both associated with longer telomere lengths and that inhibits telomerase expression in cancer cells is Vitamin D3.   The 2007 paper Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women reports ”Serum vitamin D concentrations were measured in 2160 women aged 18–79 y (mean age: 49.4)  – Serum vitamin D concentrations were positively associated with LTL (longer telomere length) (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging.” Yet, D3  is another substance that can help inhibit the expression of telomerase in cancer cells as pointed out in the 2003 publication Combination treatment with 1alpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells.  Also, see Induction of Ovarian Cancer Cell Apoptosis by 1,25-Dihydroxyvitamin D3 through the Down-regulation of Telomerase.

Resveratrol is another supplement substance that seems to have a dual personality, on the one hand associated with enhancing telomerase activity in healthy cells(ref)(ref) and on the other hand inhibiting expression of telomerase in cancer cells(ref)(ref).   

The active ingredient in green tea EGCG appears to be yet another dietary substance with the dual personality characteristic.  Drinking ample quantities of green tea appears to slow down age-dependent telomere shortening on the one hand(ref),  and EGCG represses telomerase expression in cancer cells(ref)(ref).  I am sure the same point can be made for other substances in the anti-aging supplement regimen.

Telomerase regulation is in fact a very complex process(ref).   As I have put it in my treatise “These results suggests to me that telomere shortening is a complex process involving a balance of shortening due to cell division, lengthening due to natural telomerase expression and perhaps cell replacement due to differentiation of stem cells. And these in turn are affected by many lifestyle and dietary factors and moderated by cell-signaling feedback loops.” 

Yet, it could well be the case that management of telomere length is our best hope for realizing extraordinary longevity in the nearer future.  The 12th theory of aging in my treatise Telomere Shortening and Damage forwards the hypothesis that longer telomere lengths are likely to be correlated with longer lifespans and that keeping one’s telomeres as long as possible through expression of telomerase is vital for health and longevity. Telomeres and telomerase are among my favorite subjects for treatment in this blog.  Among the many relevant blog postings are the recent postings Exercise, telomerase and telomeres, Timely telomerase tidbits, Breakthrough telomere research finding, and Telomere and telomerase writings. And, as time proceeds, I expect there will be more.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career. I have been at this part-time for well over a decade, and in 2007 this became my mainline activity. In earlier reincarnations of my career. I was founding dean of a graduate school and a university professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com.
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51 Responses to Vitamins, supplements and telomerase – upregulation or downregulation?

  1. MG63 says:

    Hello — I’m new to this group and would appreciate any guidance on timing my supplement intake to avoid canceling out benefits below is my regime. thanks

    -Before Breakfast

    NAC (on an empty stomach to boost Glutathione levels)

    -w/Breakfast

    Resveratrol 250mg (Revgenetics)

    Quercetin 250MG

    Curcumin (250MG)

    Fish oil (500MG DHA)

    Multivitamin

    Fruit Drink with Blueberry, BillBerry. POM

    Saw Palmetto

    7 Keto

    ALA

    D3 (1,000mg)

    Vitamin C (1,000mg)

    Alpha-GPC

    Carnosine(250mg)

    Taurine (500mg)

    Milk Thistle

    DIM / I3C

    CoQ10 (50mg)

    - Lunch

    Fish oil (500MG DHA)

    Multivitamin

    Alpha-GPC

    CoQ10 (50MG)

    Whey (25grams of Protein)

    - Dinner

    Red Rice Yeast w/ CoQ10 (100MG) (for cholesterol)

    Milk Thistle

    ALA

    Multi-vitamin w/ C (1,000mg)

    DIM / I3C

    Saw Palmetto

    Carnosine(250mg)

    Taurine (500mg)

    Curcumin (500mg)

    - Before bed

    Melotonin

    Lemon Balm

    Astragaloside IV (from Revgenetics)

  2. admin says:

    Hi MG63

    I am afraid not much is known about the timing/supplement conflict/bioavailability issue. At lease not much is known to me. I have a few comment:

    - Since curcumin may possibly inhibit the effect of Astragaloside IV, you might want to bump it up to lunch instead of at supper.

    - A question for you. Now that Revgenetics is no longer selling astragaloside IV or cycloastragenol, where will you get a purported telomerase-inducing supplement?

    - I don’t see alpha-lipoic acid on your list, a substance powerfully synergistic with ALA in its actions on mitochondria. I take a combined ALA and alpha-lipoic acid tablet early in the day. Subjectively, I think it helps keep my head clear for hard thinking.

    - I took NAC for a while and then discontinued its use. You could check out my note on the subject at http://www.vincegiuliano.name/Antiagingfirewalls.htm#N-Acetyl Cysteine

    Hope this is helpful
    Vince

  3. MG63 says:

    thanks Vince.

    I take ALA in the morning and evening. Per the Astragaloside IV, they are liquidating the supply so I purchased three bottles. Going forward, I’m not sure where to purchase. I did find a site that sells it, but I do not know anything about them. http://www.terraternal.com. Would it be advisable to take Astragaloside IV at lunch and then keep the curcumin with breakfast and dinner. Breakfast for me is at 6:00am, lunch 12:00 and dinner 5:30/6:00.

    As for NAC, I was looking for something to help with Glutathione production. I tried a Glutathione Patch and investigated OSR1. http://www.leesilsby.com/osr.php

  4. MG63 says:

    In your opinion, which is more effective on telomerase – astragaloside IV or cycloastragenoll? Since RevGenetics is selling 5mg of Cycloastragenol at a discount I was going to stock-up but was not sure if it was worth the investment. thanks.

  5. admin says:

    Hi MG63

    I do not know the answer to your question and I know of no research that definitively answers it. Nor am I sure exactly how effective each is. I strongly suspect that both may confer longevity benefits, possibly important ones, such as related to somatic stem cell proliferative survival. I also expect that while they may slow age-related or disease-related telomere erosion that in fact they do NOT generally extend telomeres. If TA65 did extend telomeres, now, after two years, we should be able to see some published clinical data to that effect. Instead, there appears to be only a few anectdotal stories.
    It may be that these substances are no more effective for keeping telomeres long than the popular supplements like vitamins D3 and E mentioned in this blog post. It is important to pay attention to serious published research despite the hope and hype.

    Vince

  6. admin says:

    MG63, regarding your January 22 post:

    I too have been purchasing Astral Fruit from Revgenetics, but now that it is discontinuing selling cycloastragenol because of violating the Geron patent I will have to find another supplier. Fortunately I have a few bottles of it left. I do not know about http://www.terraternal.com but will look into it.

    I take my telomerase activator around 5 or 6PM and take my resveratrol, green tea extract, curcumin, etc in the morning and just before bedtime with a snack, the objective is to separate the times by 5-6 hours. Most days I can do this. I will read your suggested post re. Glutathione.
    Vince

  7. Lee says:

    In your Firewall Supplements, you mention either 5mg of the cycloastragenoll or 100mg astragaloside IV …are those differing quantities providing approximate equivalence in your opinion? If the T65 uses about 100mg, is your guess then that the Astragaloside IV may be approximately the same as the T65?

    You also mention taking separately the astralagus extract stand 0.5%, and if you don’t mind saying who you source for that? What additionally do you think that might add to the regimen?

    Thanks

  8. admin says:

    Hi Lee

    You are asking about a question that has been long-debated.See the long discussion thread on the substance at
    http://www.imminst.org/forum/index.php?showtopic=19921&st=460&p=340089&#entry340089

    The original TA65 dose was 5mg, and oeople paid $25,000 a year for the original Patton Protocol. That was for only 6 months of treatment. Now there has been rumors that they have upped the dose to 100mg. However the TA sciences webpage http://www.tasciences.com/ta65molecule.html
    still says that the capsules are 5mg.

    What TA65 consists of is a proprietary secret to TA Sciences. However the Geron patent related to astragalus-based telomerase activators is in the public domain. Based on what is said in the patent, 100mg of astragaloside IV and 5mg of cycloastragenol have the same telomerase-activating capability. So, the main speculation has been that TA65 is cycloastragenol, although that is not for certain.

    I am now taking both cycloastragenol purchased from Revgenetics and a Natures Way astragulus extract. I am taking the astragalus extract because most of the considerible literature on beneficial effects of astragalus are for astragalus, while there is no real medical literature on the highly specific cycloastragenol component. Only what is in the Geron patent.

    Vince

  9. Lee says:

    Many, many thanks for bringing me up to speed so quickly on this issue.

  10. MachineGhost says:

    I would move the Carnosine and Taurine to before breakfast (at least one hour) and before bedtime (at least two hours after dinner). They are free form amino acids and do not need the competition from other foods or minerals for absorption. Carnosine should also be a 500mg dose to overcome the degrading enzyme.

    I agree with the poster that there should be more time between the telomerase inhibitors and the IV. 5-6 hours just is not enough; it should be 12 hours minimum.

    Your D3 dose is likely meaning to be 1000 IU not 1000 mg (40000 IU). Even so, 1000 IU is woefully insufficient as the human body uses around 5000 IU a day.

  11. admin says:

    Hi Machineghost

    In fact, I do take carnosine before breakfast and before bedtime at the 500mg level. I should probably make that clearer in my regimen listing.

    I have switched to cycloastragenol from astragaloside IV but I agree that it would be better to allow more time between taking it and the purported telomerase inhibitors, like 12 hours. I don’t quite know how to do this practically, however, without reducing my dosings of those inhibitors like resveratrol and fish oil down to once a day. Since I have come to look to them for multiple positive effects I have so far hesitated to cut back on them. Actual scientific data on the results of taking telomerase activators is very scarce as you probably know, while the results of taking the other substances are much better studied. I am open to learning more about this topic.

    As to D3, you are right on both counts. I have been doing 4,000 iu a day and need to update my treatise accordingly.

    Vince

  12. Michael says:

    Vince,

    All the discussed substances are anti-inflammitary in nature
    and chronic inflamation causes telomere erosion.

    They may not be increasing Telomerase expression but simply reducing erosion.

    Just a thought.

    Mike

  13. admin says:

    Mike
    You are correct about these substances, anti-inflammatories and antioxidants, helping to prevent telomere errosion. In fact, in the right circumstances some of them may contribute to telomere lengthening. Over the last year I have come to see telomere length maintenance as ever more-important matter but also as requiring a complex multifacated approach. Taking a “telomerase activating” supplement may be less important than a lot of other measures, including regular exercise. I have sought to express that viewpopint in my blog writings and in my treatise.
    Vince

  14. Philip Terry says:

    Hello,

    I had a long conversation with assistant of the lady who discovered Telomerase and learned about their latest projects. Apparently those who meditate had longer telomeres than those who don’t – and also saw a video which correlated the various stress/ adrenal hormones to telomere shortening in care givers for ill children… I wonder if the power of controlling the mind exhibits more of a benefit than taking telomere activators…?

    Vince, have you heard of these: http://www.sirtrispharma.com/pipeline.html

    Glaxo is pouring massive money into these which is very good sign. Deriving from Reservatrol.

    PS. I have seen excellent results after regular intake of raw purple kale (blended)

    Thanks

  15. admin says:

    Hi Philip Terry

    Yes there is a fair amount of literature on stress minimization and longer telomeres, I mention some of that in my treatise. And yes, you may be right that the power of the mind coupled with low stress may do more than the so-called “telomerase-activators.” There is quite a discussion of this in my treatise at http://www.vincegiuliano.name/Antiagingfirewalls.htm#Telomereshorteningtheory Also check out the firewall discussion for the Telomere shortening theory for where I am on telomerase activation.

    As to Sirtris Pharma, I mention them in my latest blog entry SIRT1, mTOR, NF-kappaB and resveratrol amd in another long blog post still in the works.

    Raw purple kale? Yum. Chack out the blog entry I posted last week on the active ingredient, Fucoidan.
    Vince

  16. Philip Terry says:

    thanks a lot Vince – fantastic reading here… this now ranks as one of my fav sites…

    Do you have any other info on the effect of protein, carb and fat intake on telomere expression? I am thinking about your post on how all the pieces of the puzzle fit together.

    Lately I have cut right back on carbs and fats (but not to the point I sacrifice nutrients), increased the amount of omega 3 foods as above and seen noticeable improvements in skin/ muscle tone over last two weeks.
    I am assuming this reduces lipid oxidation and glycation which I imagine will have a knock on positive impact on telomeres… Do you have any latest news on what type food/ diet and how often in order to optimize telomere expression?

    PS. I completely swear by the benefits of raw ‘purple kale’ puree (amazed no company has started marketing it yet). I think Lutein is another operative ingredient. A good post on this blog about it: http://inhumanexperiment.blogspot.com/2009/04/lutein-for-skin-elasticity-hydration.html

    Thanks again

  17. admin says:

    Philip Terry

    I have no information regarding diet and telomerase expression beyond that I have published. I suspect we will see studies on that subject coming out in the next 6 months given the accelerated interest in telomeres though, and I will be on the lookout for them. I suspect that, given the way things are interconnected, that diets known to be healthy and contribute to longevity probably also result in less telomere errosion. Personally I like Mediterranean diets. Have you seen my blog entry Recent research on the Mediterranean diet? It is at http://anti-agingfirewalls.com/2009/08/31/recent-research-on-the-mediterranean-diet/

    And, as to purple kale,did you see my blog entry on the active ingredient Fucoidan? It is at http://anti-agingfirewalls.com/2010/03/13/fucoidan/

    Vince

  18. Philip Terry says:

    Thanks a lot Vince… I am pretty much on this diet too. Cannot stress the importance of vegetable intake in our crusade. I try to get 5 different colours in each meal to get a continual stream of phytonutrients. I understand each colour represents a different protective phytonutrient. I am bias towards all that are purple! I think they are high in Anthocyanins. My firewall strategy is to measure what works well and get better at taking it. For example ACAI, purple kale and Spirulina are formidable weapons in my anti-aging aresnal therefore I would rather substitute those ingredients over something less favourable. I am also researching bioavailability and how I can get the benefit from these ingredients even further.

    I am on your side with the diligent supplement taking although my budget does not permit fully protective armoury (just yet!). But what is your opinion on journalists like this who knock them?
    http://www.newscientist.com/article/mg19125631.500

  19. admin says:

    Hi Philip
    I love ypur using colors to separate out phytochemicals. As for me I love blue/purple in wild blueberries, flaming red in hot peppers (capsicum), green and black in tea, white in garlic and day-glow orange in curcumin/turmeric.
    I like your strategy of going with what works.

    As to the commentator, I am afraid she is simply not up on her facts. There is a very large body of literature out there supporting the efficancy of many supplements, literature written by serious researchers, not “vitamin freaks” or selling sites which do in fact often make ungrounded claims. True some supplements have been overhyped and studies also exist showing negative results. I have reported on some of these here in my blog. If you do a search here on the term “antioxidant” you will find a lot to read. And I document everything as you probably note.

    Vince

  20. jeff says:

    Im wandering if any of youall experienced hair regrowth on Astragaloside 4 and wandering if the new Cycloastrageno has the same effect

  21. admin says:

    Hi Jeff

    I don’t really know for sure. It seems like there is a slow increase in the number of grey hairs. But hair follicles turn over very slowly so this should not be surprising. I am finishing a long new blog entry on “Telomerase activators – what do they really do?” and I report there in detail on both research and my personal experience. Should go online later today or tomorrow.

    Vince

  22. andrew says:

    Hi Vince. What are your thoughts on supplementing with SAMe, b-complex and methylcobalamin to increase glutathione levels and telomere length? I blieveLife Extension published an article on the subject during the summer of 09. I’m wondering why you don’t include this in your anti-aging firewall.

    Peace,

    Andrew

  23. Philip Terry says:

    Hi vince,

    Does telomere shortening stem from ROS in the mitochondiral respiratory chain? I am trying to keep going back to see what cause of aging has the most downstream consequences? To me this is the most important strategy. And attack from that angle by using the 80:20 rule. It seems the deleterious effects of ROS in mitochondria? Therefore getting the perfect proportion of fats and carbs as they are processed seems to be critical. I have learned not to overload on carbs (excessive glucose in the blood stream) as this induces a backlog of stress at the gates of the mito. Then again too much fat is more reactive than glucose so getting the perfect ratio of fats while allowing just enough glucose to beat the fats at the gates of the mito?? I understand monounsaturated fat is very important too as this makes LDL less reactive by upregulating HDL and transporting it out of the arteries. I am on low carb diet at the moment but I am exploring how to get the perfect proportion of fats…

    Check this out:
    Improvement of mitochondrial function results in less telomeric damage and slower telomere shortening, while telomere-dependent growth arrest is associated with increased mitochondrial dysfunction

    http://nar.oxfordjournals.org/cgi/content/full/35/22/7505

    Best regards

    Philip

  24. admin says:

    Hi Philip
    Regarding your question, the paper you cite seems to sum up what is known and still unknown, an excellent citation. There appear to be feedback loops relating miotochondrial health and cell senescence So, ROS in mitochondria or other forms of cell stress can lead to shorter telomeres and move a cell towards senescence. Also, it is possible that telomerase expression can protect against oxidative stress. The exact mechanisms are unclear and, I believe, it is unclear how many of the observed effects occur in mature cells and how many result from affecting the differentiation of adult stem cells.

    I think looking for what has the greatest downstream consequences is a great idea. However in cells the reactions are highly networked and it it is not always easy to tell what is upstream and what is downstream and these distinctions may not make sense. In any event I think maintaining a strong antioxidant defense in mitochondria is very important and as you know I employ a number of supplements particularly for that purpose. And of course keeping carbs down is very important.

    As you learn more about how to optimize your ratio of fats to carbs, I would love to hear about what you are discovering.

    Vince

  25. admin says:

    Hi Andrew

    My first thought about your question is that I probably have not thought about that enough. Of course, both b-complex vitamins and especially B-12 are in the supplement regimen in my treatise. I think they produce general benefits in stress reduction but I am not aware of research specifically relating their impacts on telomere lengths. I have not included SAMe in the published regimen (which is the same as my own) because I have thought it to be generally redundant of substances already there for most people. On the other hand I have suggested that my wife take it for particular reasons, and she does. I will be giving it another look.

    Vince

  26. Philip Terry says:

    Hi Vince,

    I will keep digging and keep you updated.

    Maybe you have already linked these themes – Lipolysis – the metabolism of fat is triggered off by cortisol, epinephrine, and norepinephrine. These just happen to be the exact same hormones responsible for telomere erosion. Elissa Epel’s slides on youtube show a direct correlation between these precise hormones above going into overdrive and short telomeres – in carers who constantly look after sick people. I bank **MOST** of the damage to telomeres is being done during the metabolism of fat inside the mitochondria or an incorrect balance of fat omega 3 to omega 6.

    It seems the integrity of the inner mitochondria wall is critical in dampening some of the effects of ROS – Omega 3 EPA fatty acids benefit the inner membrane tremendously in this study. This explains why omega 3 relates to telomere extention.

    http://www.spacedoc.net/aging_omega3

    Vitamin D apparently transports calcium out of the mitochondria.¨That explains that one.

    Thought you might also like this article – they also mention that it’s deleterious downhill spiral from the mitochondria integrity.

    ” The identification of the specific molecular components and mechanisms linking p53 and mitochondrial dysfunction would provide a unifying basis for a central axis of ageing, linking genotoxic stress to stem-cell compromise, mitochondrial decline and, ultimately, organ atrophy, functional decline and the diminished energy production that typifies essentially all aspects of cellular and physiological decline in ageing organisms.”

    http://www.nature.com/nature/journal/v464/n7288/full/nature08982.html#f3

    What an exciting journey!

    Let me know if you have any ideas to add so I can follow the right footpaths. I am going to make some calls to American scientists and do go deeper into this.

    Philip

  27. admin says:

    Philip

    First of all, I very much appreciate your research observations and they are of a quality that are most welcome here.

    If you are correct, and you could well be,it suggests that focus on mitochondrial health and proper Omega3 -Omega 6 balance are key anti-aging strategies. As you probably know I think these are very important but I think other strategies are important too. And yes, data on stress hormones, telomere erosion, and mitochondrial lipolysis do seem to make up a pattern.

    There seems to be a fair number of research publications relating EPA/DHA to mitochondria, but looking at the results of the search
    http://www.google.com/search?hl=en&q=EPA+DHA+mitochondria&start=10&sa=N

    I get the impression that most of it is more than 5 years old. The subject seems to gone out of research style.

    I did however come across an interesting 2009 presentation on PUFAs at
    http://www.anslab.iastate.edu/Class/AnS419/AnS419_Lecture18.pdf

    As to the citation from Nature “Linking functional decline of telomeres, mitochondria and stem cells during ageing,” you are absolutely right. Aging is clearly a systems process and the paper does seems to offer a good first-cut at such a view. I need to study it further. As a matter of fact I will be offering a presentation on a Systems View of Aging at the upcoming meeting of the American Aging Association in Portland Oregon in June. So I will be comoing up with a blog entry soon on that topic.

    It is an exciting journey. I wish I could tell you what the right footpath is, but now it appears that there are several that generally lead in the right direction.

    Please keep your good contributions coming.

    Vince

  28. andrew says:

    Very interesting article in today’s sciencedaily linking the longevity molecule to lithocolic acid:

    http://www.sciencedaily.com/releases/2010/09/100915100935.htm

    Titorenko and colleagues screened more than 19,000 small molecules to test their ability to extend yeast-lifespan. Under both normal and stressed conditions, LCA had a major impact.

    “Our findings imply that LCA extends longevity by targeting two different mechanisms,” says first author Alexander Goldberg, a Concordia doctoral student. “The first takes place regardless of the number of calories and involves the day-to-day or housekeeping proteins. The second system occurs during calorie-restriction and involves stressor proteins.”

    “Regardless of their triggers both of these mechanisms work to suppress the pro-aging process,” he continues.

    Alternate studies indicate that lab animals live longer when fed a LOW PROTEIN DIET which INHIBITS LCA production:

    http://grande.nal.us…s&therow=269644

  29. andrew says:

    Any thoughts on the LCA research Vince?

  30. admin says:

    Andrew:
    I looked at the Science Daily article but still want to look at the original journal article. Whether LCA will cause life extension in mammals is yet to be seen. As the article says, LCA is a human hormone not expressed in yeast, so the life extension effect in yeast could be a hormetic effect. Did you notice a link on the same Science Daily page to a 2008 article pointing out that LCA activates the vitamin D receptor, at http://www.sciencedaily.com/releases/2008/03/080314165355.htm ?

    The bile acids appear to be interesting and I may choose to do a blog entry on them.
    Vince

  31. andrew says:

    Yes I did notice the link pointing out that LCA activates the vitamin D receptor–I just read the article a few days ago. I’ll be on the lookout for your blog entry on the bile acids.

    I thought you might be interesting in the following study:

    Glucosamine causes the death of pancreatic cells

    Glucosamine causes the death of pancreatic cells
    This release is available in French.

    Quebec City, October 27, 2010—High doses or prolonged use of glucosamine causes the death of pancreatic cells and could increase the risk of developing diabetes, according to a team of researchers at Université Laval’s Faculty of Pharmacy. Details of this discovery were recently published on the website of the Journal of Endocrinology.

    In vitro tests conducted by Professor Frédéric Picard and his team revealed that glucosamine exposure causes a significant increase in mortality in insulin-producing pancreatic cells, a phenomenon tied to the development of diabetes. Cell death rate increases with glucosamine dose and exposure time. “In our experiments, we used doses five to ten times higher than that recommended by most manufacturers, or 1,500 mg/day,” stressed Professor Picard. “Previous studies showed that a significant proportion of glucosamine users up the dose hoping to increase the effects,” he explained.

    Picard and his team have shown that glucosamine triggers a mechanism intended to lower very high blood sugar levels. However, this reaction negatively affects SIRT1, a protein critical to cell survival. A high concentration of glucosamine diminishes the level of SIRT1, leading to cell death in the tissues where this protein is abundant, such as the pancreas.

    Individuals who use large amounts of glucosamine, those who consume it for long periods, and those with little SIRT1 in their cells are therefore believed to be at greater risk of developing diabetes. In a number of mammal species, SIRT1 level diminishes with age. This phenomenon has not been shown in humans but if it were the case, the elderly—who constitute the target market for glucosamine—would be even more vulnerable.

    “The key point of our work is that glucosamine can have effects that are far from harmless and should be used with great caution,” concluded Professor Picard.

    The results obtained by Picard and his team coincide with recent studies that cast serious doubt on the effectiveness of glucosamine in treating joint problems.

    ###This study was co-authored by Mathieu Lafontaine-Lacasse and Geneviève Doré.

  32. I have recently joined a gym and the instructor suggest me to take some medicines.I think they all are Vitamin Supplements.So I am a bit confused,are these safe for my health.I never tried it in previous.
    Thanks for this blog.

  33. admin says:

    Vitamin Supplements

    Wow. You are asking a question that would take a large book to answer. I think most vitamins are safe for your health IF proper dosages are followed and IF you are not taking contraindicating drugs and IF you do not have a contraindicating disease condition and IF you don’t have some contraindicating genetic abnormality. To see what I have to say about supplements you can read my treatise at http://www.vincegiuliano.name/Antiagingfirewalls.htm.
    Vince

  34. admin says:

    andrew:

    Thanks for sharing the news release about the Picard work. Since glucosamine is part of my supplement regimen I am very concerned about its effects on insulin-producing pancreatic cells and its relationship to SIRT1 expression. I would like to learn more about what glucosamine does at more normal doses. I am putting this issue into the hopper for my next round of research for blog entries.
    Vince

  35. he U.S. Food and Drug Administration says Vigor-25, a product marketed as a natural dietary supplement to enhance male sexual performance, should not be purchased or used because it contains sildenafil, the active ingredient in the prescription drug Viagra.

  36. admin says:

    Claudine

    I saw that on your site. Thanks for the heads-up.

    Vince

  37. Kevin says:

    You all were taking Cycloastragenol for over an year now.
    Did you see any side effects?
    Revgenetics recommend to take Cycloastragenol for 15 days and then 15 days break.I am taking 2 capsules(5mg) for almost a month now. I feel much better with energy and my skin is getting better. I am 40. I bought Cycloastragenol recently from BiologixPeptide.com. They are $88 for 2 months supply but it says for lab use only. How long should I take Cycloastragenol?
    How much off period is recommended?
    I appreciate your guidance and help.

    Thanks
    Kevin

  38. Steve says:

    Noticed at the top of the page, even though it’s old, some talk about ALA. Just wanted to add, if anyone’s taking an ALA supplement that the R-ALA has shown to be several times more effective than just ALA (R-ALA + S-ALA) and is no more expensive. It is like the difference between CoQ10 and Ubiquinol, the latter is the biologically active form and the one more easily utilized by the body.

    Lots of great telomere information here, thanks for your site I will definitely bookmark it.

  39. admin says:

    Steve

    Your point about the superior bioactibvity of R-ALA is well-taken.

    Thanks
    Vince

  40. admin says:

    Kevin

    For their presumed telomerase-activating effects, I took astragaloside IV for nearly two years and then a low dose of cycloastragenol (5mg a day) for nearly a year but, except for occasional use, have discontinued taking these supplements. My reasons are several:

    1. It is unclear to me in terms of published results that there is a clear health benefit to taking these substances. Many other factors impact on telomere lengths and it appears that the impact of taking cycloastragenol is relatively weak in health individuals. For people with certain deficiencies such as T-cell senescence brought on by HIV or cytomegalovirus, it is likely to be more valuable. Have you seen the publication at http://www.ncbi.nlm.nih.gov/pubmed ?

    2. I have over the last two years learned a lot more about cell senescence and its causes and see short telomeres more as a symptom of other senescence-promoting causes than itself as a driving factor for cell senescence, or for aging itself.

    3. The health-producing effects of a great many of the other supplements I take are well-established in the published literature and I do not want to give them up for days at a time for the relatively unproven benefits of taking cycloastragenol.

    4. On careful consideration, it is unclear that taking the substance provided me with any health benefits, though it could have.

    5. If I had an inexpensive source of pharmaceutical-grade cycloastragenol and its benefits did not require not taking other supplements, I would probably be still taking it. As matters stand, it does not appear worthwhile for me to do so.

    Has the cycloastragenol you are taking been tested to make sure it is free of impurities like heavy metals?

    Vince

  41. andrew says:

    Dear Vince,

    I read your revised nutritional supplementation list.

    I was wondering:

    1. Does your b-complex contain nicatinomide or niacinamide? I know that you’ve frowned on these two b-complex constituents in the past. What brand of b-complex do you use?

    2. Do you take a multi vitamin? If so what brand?

    3. Have you considered re-introducing NAC into your regimen? Recent studides indicate that NAC does not cause mycardial infarction.

    4. Is SAMe on your radar? It supportst brain, joint and liver health… I’m sure you could write a thesis on the subject!

  42. Andrew:

    Regarding your questions:
    Dear Vince,

    I read your revised nutritional supplementation list.

    I was wondering:

    1. Does your b-complex contain nicatinomide or niacinamide? I know that you’ve frowned on these two b-complex constituents in the past. What brand of b-complex do you use?

    Yes. It is almost impossible to find a B-complex supplement that does not contain a small amount of one or tje other, I have been somewhat promiscious with regard to shopping for B-complex pills, trying for a supplement that does not drive me over 900mcg of folic acid if I take it twice a day.

    2. Do you take a multi vitamin? If so what brand?

    I do not.

    3. Have you considered re-introducing NAC into your regimen? Recent studides indicate that NAC does not cause mycardial infarction.

    I have not used it regularly but have a bottle of it and use it if and when I feel need a slug of extra-powerful antioxidant. I would use if, for example, if I ever had to have a CAT-scan ( which I avoid when possible) or if I knew I were exposed to some toxic metal.

    4. Is SAMe on your radar? It supportst brain, joint and liver health… I’m sure you could write a thesis on the subject!

    It is on my radar and I have encouraged my wife to take it in the past. Goog suggestion! Don’t know when I can get to it since I have a very full plate now

    Vince

  43. Alma H. Bond, Ph.D. says:

    I am a psychoanalyst and much published author who is currently planning to write a book on life extension. I am interested in interviewing people who have taken TA-65. If you are such a person and would like to be interviewed, please contact me at almahb@aol.com. Thank you,
    Alma H. Bond, Ph.D.

  44. andrew says:

    Hi Vince.
    I’ve always considered carnosine one of the “benign guys” in my supplement arsenal, a non-toxic sweetheart.

    I just read a disturbing piece of information that has me re-thinking whether or not I should continue using carnosine(1000mg daily).

    What are your thoughts on the neurotoxic condition known as carnosinemia? Is there trouble in paradise for those of us who supplement w/ carnosine?

    http://metabolicresearch.org/10001/20401.html

  45. Wellness says:

    New Clues About Aging: Genetic Splicing Mechanism Triggers Both Premature Aging Syndrome and Normal Cellular Aging:
    http://www.sciencedaily.com/releases/2011/06/110613121956.htm

  46. Pingback: Telomerase update –arguments for and against using telomere extender supplements | AGING SCIENCES – Anti-Aging Firewalls

  47. philipjterry says:

    Hey Vince

    I forgot to take my stroll in the sun and vitamin c tablet this morning. Sometimes I get so deeply entrenched in the intricasies that I overlook the core fundamentals that are indeed the most powerful weapons in the anti aging arsenal :)

    I was wondering why you don’t have the following supplements in your supplement aresnal?

    Bacoba?
    Ginseng?
    Astaxanthin

    Ginseng came up trumps in this citation with a tick in every positive box:

    http://www.lef.org/magazine/mag2012/may2012_Nutrient-Cocktail-Delays-Aging-Extends-Life-Span_01.htm

    one of my strategies now is to be very efficient with my time, since discovering the gold nugget insights now is a key in itself in the antiaging aresenal.

    Hope all is well….

    Philip Terry (back on the case since our last correspondance two years ago above)

  48. Alain28 says:

    Blood leukocytes are a heterogeneous mixture of cell types whose telomere lengths differ greatly, reflecting variation in stem cell turnover and recruitment, expansion and replacement of more mature cell types as well as variable telomere loss and telomere repair. These differences in cell and telomere length dynamics, together with the evidence that telomere length is influenced strongly by genetic polymorphisms, greatly complicate the interpretation of claims that socio-economic status modulates the rate of telomere attrition.

    http://www.ncbi.nlm.nih.gov/pubmed/17081156

    That explains the difference in leukocyte length.
    Because stem cells are found in the bone marrow, blood and lipid cells.

  49. Alain28 says:

    So that doesn’t mean a telomerase activator wouldn’t be beneficial for other cell lines.

  50. Alain28 says:

    And about the use of high polyphenol foods as a telomerase inhibitor in normal cell lines, wouldn’t that be pro-aging? Imagine what would happen to our reproductive cells (sperm and eggs), every animal then would go extinct soon. There are vitamins and herbs known for slowing down telomere loss due to a weak telomerase expression. We need to find a chemical that has a very strong signalling on telomerase expression (often also dose dependent) to reverse the telomere loss completely. Perhaps astragaloside iv or cycloastragenol can.




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