Exercise, telomerase and telomeres

A new study reported in the press this week looks at the relationship of exercise to expression of telomerase and telomere lengths in athletes and non-athletes.  Other studies on the same topic have appeared in the last year or so.  My purpose here is to review these studies in the context of some earlier studies. It is not just a simple matter of “the more and the harder the exercise, the better.”

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. I have devoted numerous blog entries to telomeres and telomerase, including most recently Timely telomerase tidbits, Breakthrough telomere research finding, and Telomere and telomerase writings. On the other hand, it is also well established that regular exercise is also strongly supportive of longevity(ref)(ref)(ref).  The mechanisms through which exercise improves health and life expectancy hitherto appeared to be complex and unclear.  The new research suggests that telomere extension may be a key mediator of the health and longevity benefits of regular exercise.

Sustained exercise can keep leukocytes younger

The latest study, an e-publication dated January 8 2010 from a University of Colarado group, is Leukocyte Telomere Length is Preserved with Aging in Endurance Exercise-Trained Adults and Related to Maximal Aerobic Capacity.  “To determine if age-associated reductions in TL (telomere length) are related to habitual endurance exercise and maximal aerobic exercise capacity (maximal oxygen consumption, VO(2)max), we studied groups of young (18 – 32 years; n = 15, 7m) and older (55 – 72 years; n = 15, 9m) sedentary and young (n = 10, 7m) and older endurance exercise-trained (n = 17, 11m) healthy adults. Leukocyte TL (LTL) was shorter in the older (7059 +/- 141bp) vs. young (8407 +/- 218) sedentary adults (P < 0.01). LTL of the older endurance-trained adults (7992 +/- 169bp) was approximately 900bp greater than their sedentary peers (P < 0.01) and was not significantly different (P=0.12) from young exercise-trained adults (8579 +/- 413). — Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the “anti-aging” effects of maintaining high aerobic fitness.”

So, older folks who vigorously exercise keep up their leukocyte telomere lengths and folks who sit around watching TV instead do not.  This message seems repeated in several other research reports. A 2009 study, this time from a German group, is: Beneficial Effects of Long-term Endurance Exercise on Leukocyte Telomere Biology.  “This study examines telomere biology and senescence-associated factors in endurance athletes and matched controls without physical activity. –Methods: Leukocytes where isolated from the peripheral blood of professional young track & field athletes (n=32, age 20.4 years, running 73±5 km/week), aged athletes performing regular endurance training (n=25, age 51.1 years, running 80±8 km/week, 35 years training history) and two control groups of age-matched, physically inactive healthy volunteers (26 young and 21 aged subjects).  –Results: Telomere repeat amplification protocols revealed an activation of leukocyte telomerase in young athletes to 256±19% and in elderly athletes to 182±11% compared to controls. Western blots showed an up-regulation of the telomere-capping protein TRF2 in young (179±1%) as well as in aged athletes (176±10%). FlowFISH assays and real-time PCR measurements of leukocyte telomere length showed no difference between young athletes and young controls. Sedentary elder controls exhibited a significant reduction of leukocyte telomere length (FF: 53±3%; PCR: 70±8%; vs. young controls). Importantly, there was a striking conservation of telomere length in aged athletes (FF: 88±4%; PCR: 84±7%; vs. young controls). Further analysis of telomere-associated proteins and cellular senescence regulators demonstrated an increase of TRF2, Ku70 and Ku80 mRNA and a reduced protein expression of Chk2, p16 and p53 in aged athletes compared to untrained elder controls.”

More or less the same story.  Among the younger people exercise seems to have a strong effect on leukocyte telomerase expression but no effect on telomere lengths.  But in the older folks, only those who exercised kept up most of their telomere lengths.  Further, their cells showed markedly lower levels of senescence markers.  As far as leukocytes are concerned, vigorous regular exercise definitely seems to keep them young. 

A 2009 mouse and human study Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall looks a bit further at the molecular dynamics of exercise and comes to a consistent conclusion.  “Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle–checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. — Conclusions— Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.”

Watch out for your muscle satellite cells

There is a caution however, for more or harder exercise is not always better.  And leukocytes are not the only relevant cells to consider.  Earlier studies indicate that too strenuous or prolonged exercise can lead to serious depletion of telomerase in muscle satellite cells.  Muscle satellite cellsare small mononuclear progenitor cells with virtually no cytoplasm found in mature muscle. They are found sandwiched between the basement membrane and sarcolemma (cell membrane) of individual muscle fibres, and can be difficult to distinguish from the sub-sarcolemmal nuclei of the fibres. Satellite cells are able to differentiate and fuse to augment existing muscle fibres and to form new fibres. These cells represent the oldest known adult stem cell niche, and are involved in the normal growth of muscle, as well as regeneration following injury or disease.”   

Under conditions of hard exercise satellite cells can be forced into multiple rounds of duplication and differentiation leading to telomere shortening.  The 2003 publication Athletes with exercise-associated fatigue have abnormally short muscle DNA telomeres tells the story. “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. — 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. CONCLUSION: These findings suggest that skeletal muscle from symptomatic athletes with FAMS 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 2008 study The effects of regular strength training on telomere length in human skeletal muscle looked at power lifters and showed that long-term exercise is not necessarily associated with satellite cell telomere loss although lifting heavier loads mean more loss.  “These results show for the first time that long-term training is not associated with an abnormal shortening of skeletal muscle telomere length. Although the minimum telomere length in PL (power lifters) remains within normal physiological ranges, a heavier load put on the muscles means a shorter minimum TRF length in skeletal muscle.”

The effect of exercise on telomeres in satellite cells is further reported in the 2009 publication The biology of satellite cells and telomeres in human skeletal muscle: effects of aging and physical activity.  “New insights suggest that telomeres in skeletal muscle are dynamic structures under the influence of their environment. When satellite cells are heavily recruited for regenerative events as in the skeletal muscle of athletes, telomere length has been found to be either dramatically shortened or maintained and even longer than in non-trained individuals. This suggests the existence of mechanisms allowing the control of telomere length in vivo.”  Whether satellite cell telomeres get shorter or longer or stay the same with exercise depend, among other matters, on the expression of telomerase in the satellite cells as a result of the exercise, and this in turn depends on several factors including physical condition of the person and the nature of the exercise.

Finally a late 2008 study report Relationship between physical activity level, telomere length, and telomerase activity looks at the results of exercise on telomeres in peripheral blood mononuclear cells (PBMCs). A Peripheral Blood Mononuclear Cell (PBMC) is any blood cell having a round nucleus. For example: a lymphocyte, a monocyte or a macrophage. These blood cells are a critical component in the immune system to fight infection and adapt to intruders. The lymphocyte population consists of T cells (CD4 and CD8 positive ~75%), B cells and NK cells (~25% combined)(ref).”  According to the report:  “The purpose of this study was to examine the relationship of exercise energy expenditure (EEE) with both telomere length and telomerase activity in addition to accounting for hTERT C-1327T promoter genotype. — Sixty-nine (n = 34 males; n = 35 females) participants 50-70 yr were assessed for weekly EEE level using the Yale Physical Activity Survey. Lifetime consistency of EEE was also determined. Subjects were recruited across a large range of EEE levels and separated into quartiles: 0-990, 991-2340, 2341-3540, and >3541 kcal x wk(-1). Relative telomere length and telomerase activity were measured in peripheral blood mononuclear cells (PBMC). — CONCLUSION: These results indicate that moderate physical activity levels may provide a protective effect on PBMC telomere length compared with both low and high EEE levels.”

These studies leave me tentatively concluding:

·        Regular mildly cardiovascular exercise is likely to protect telomere lengths with aging across the three cell categories studied.

·        Vigorous aerobic exercise approaching “maximal aerobic exercise activity” may further serve to keep telomere lengths at youthful levels in leukocytes.

·        However, excessively strenuous exercise such as lifting very heavy weights or leading to exercise-associated fatigue may lead to compromised telomere lengths in muscle and/or PBMC cells and be life-shortening.

So, I believe moderation should be the rule.  See the suggestions for regular exercise in my treatise.

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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19 Responses to Exercise, telomerase and telomeres

  1. singularityFan says:

    I’m training for a marathon now and I’m up to 15 miles in 2 hours…I wonder if sustaining training to run a marathon at a pretty fast clip (3.5-4.0 hours, fast for amateurs) may be too intense? Perhaps the tipping point where this cardiovascular exercise becomes more deleterious might be when the super-marathon training regimen is reached (something like 50 or more miles) – which I have no plans to reach.

    FYI: I have this blog on my Google feed reader, so perhaps I don’t register as a unique visitor anymore – but I anticipate your posts every day. Just wanted to show support and let you know that these continue to be extremely informative and inspirational posts – they are a strong source of motivation for my exercise and supplement regimen in particular, as well as my continual fascination with biomedical gerontology in general.

  2. admin says:

    Hi Singularityfan

    I think your wondering is good. Of course I don’t have the answer since it depends on your makeup and physical condition. I admire your capability to participate in those marathon events. I also wonder what the stress might be on your PBMC and muscle satellite cell telomeres. Should you experience signs of exercise-associated fatigue, if I were you I would cut back. “Symptomatic athletes reported a progressive decline in athletic performance, decreased ability to tolerate high mileage training, and excessive muscular fatigue during exercise.” I would also take exercise-associated muscle cramping as a sign of such fatigue. See http://www.divefitness.com/html/articles/article_pdfs/EAMC.pdf

    And thanks for your positive comments on the blog. It is a labor-of-love and it is extremely important for me to know it is making a difference out there.
    Vince

  3. singularityFan says:

    Thanks for that paper, very informative.

    I haven’t experienced muscle fatigue to the point of cramps, so I think I’m probably OK, though will be vigilant for any research that comes out. I don’t want too much of a positive thing (exercise and all the physical and psychological benefits it brings) to turn into a negative thing (excessiveness that may be detrimental to my health in general and telomeres in particular).

    Will probably have to do continual research as to how long-distance running may deplete the various nutrients that I take as supplements (I take 46 pills per day, just ramping it up as I learn more, but ultimately limited by a graduate student budget presently). For example, perhaps the benefits of certain water soluble vitamins such as vitamin C (I take 4g per day) may be diminished if I need to drink extra water and expend it in the an increased volume of urine and/or sweat. I don’t know enough about physiology to have any intuition, so it’s an ongoing process.

    Such a large and complex set of issues! The information explosion due to research is impossible to keep up with, so I’ve settled (not that I have a choice) on being happy to learn whatever I can and try to hit off the main points in whatever limited amount of time and attention I can budget.

    Take care Vince,
    singularityFan

  4. jeg3 says:

    Hi Vince and SF,

    Bata alanine seems to be important for muscle functioning, I have recently been researching it and will start taking it:
    via
    http://scholar.google.com

    “The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55–92 Years): a double-blind randomized study”
    http://www.ncbi.nlm.nih.gov:80/pmc/articles/PMC2585553/
    and
    “Combined Training and [beta]-Alanine Supplementation Muscle Carnosine Synthesis, Ventilatory Threshold and Exercise Capacity in Cyclists”
    http://journals.lww.com/acsm-msse/Fulltext/2007/05001/Combined_Training_and__beta__Alanine.2250.aspx

    Thanks for your research Vince, very broad and deep.

  5. admin says:

    Singularity fan:
    “I haven’t experienced muscle fatigue to the point of cramps, so I think I’m probably OK, though will be vigilant for any research that comes out. I don’t want too much of a positive thing (exercise and all the physical and psychological benefits it brings) to turn into a negative thing (excessiveness that may be detrimental to my health in general and telomeres in particular).”

    Right. I agree that watchful prudence is likely to be the best thing. If you spot any better guidelines with respect to the telomere length issue, please let us know.

    “Will probably have to do continual research as to how long-distance running may deplete the various nutrients that I take as supplements (I take 46 pills per day, just ramping it up as I learn more, but ultimately limited by a graduate student budget presently). For example, perhaps the benefits of certain water soluble vitamins such as vitamin C (I take 4g per day) may be diminished if I need to drink extra water and expend it in the an increased volume of urine and/or sweat. I don’t know enough about physiology to have any intuition, so it’s an ongoing process.”

    This is another very interesting question, how the water consumption, sweating and higher metabolism of heavy duty exercise impacts on the bioactive half-lives of the supplements you take. Again, if you find something important out, let us all know.

    “Such a large and complex set of issues! The information explosion due to research is impossible to keep up with, so I’ve settled (not that I have a choice) on being happy to learn whatever I can and try to hit off the main points in whatever limited amount of time and attention I can budget.”

    I am afraid that is all any of us can do. As you can see in this blog I am no longer simply reporting new research results as I was a year ago, but am striving to frame them in context, essentially by writing mini-treatises on key longevity subjects. My hope is that by building up a database of these I will be working towards a framework in whioh it is easier to place emerging research results as they come in.

    Vince

  6. admin says:

    Jeg3:

    Regarding beta-alanine, I have not paid too much attention to it up to now for I have been mainly thinking of it as a precursor to carnosine and I have been doing direct supplementation with l-carnosine for something like 12 years now. It is an incredible substance. See my blog post The Curious Case of l-Carnosine at http://anti-agingfirewalls.com/2009/11/30/the-curious-case-of-l-carnosine/. I fell in love with carnosine when I learned about its ability to expand the replicative lifespan of fibroblasts by a factor of 3 and still think it is an incredible substance.

    However, it may well be the case that the bioavailability of
    beta-alanine makes it a better substance for building carnosine levels in muscles. I am going to have a hard look at your references and this issue, and will get back to you either here in another comment or in a new blog post.

    Vince

  7. admin says:

    Jeg3:

    Your comment has got me going. It appears that a number of research publications are reporting on beta-alanine for maintaining muscle carnosine and muscle strength both in atheletes and in the elderly. Could well be an important topic for both young and old. Also, there appears to be a fascinating set of similarities in behavior of beta-alanine, l-carnosine and Gabapentin in terms of actions on GABA receptors in nerves and glia. I am currently working on a blog post on the first topic and may also do one on the second topic which is both fascinating and complex. Relates to topics like pain management, maintaining mental balance, sleep and mental acuity.

    Thanks for playing this game with me.

    Vince

  8. singularityFan says:

    Vince,

    Not sure if you know about this website, but it compiles new research from leading universities.

    http://futurity.org/category/health-medicine/

    – singularityFan

  9. admin says:

    Singularityfan:

    Iwill have a look.
    Vince

  10. Philip Terry says:

    I got hooked on the concept of “10 biomarkers of vitality” muscle mass seems to positively influence all of them – someone mentioned that running had some negatives… http://www.cbass.com/Biomarkers.htm

    http://www.amazon.com/Biomarkers-Evans/dp/0130875783

  11. admin says:

    Philip Terry:
    Thanks for the interesting links. I must confess that I have never dug deeply into biomarkers and that is something I should definitely do. I am starting by ordering the book, a bargain used from the Amazon sellers listed.
    Vince

  12. I am interested in it for a long time! For example, perhaps the benefits of certain water soluble vitamins such as vitamin C (I take 4g per day) may be diminished if I need to drink extra water and expend it in the an increased volume of urine and/or sweat.

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  15. michael83727 says:

    Hi,

    I do a combination of running (what you would call “vigorous”), lighter cardio (gym bike), and weight lifting. I am wondering what in your conclusion constitutes “very heavy weights”.

    From reading elsewhere, and experience, I have found there to be a lot of health benefits from increased muscle mass. A higher resting metabolism, for one thing, helps to burn off calories and stay trim even when you are not on the trail. Stronger legs and back make running easier and should theoretically put less wear-and-tear on the bones, ligaments, cartilage, tendons.

    Also, I have read that growth hormone, which aids in tissue repair, is stimulated by weight lifting.

    So, I am wondering at what threshold the benefits of additional natural growth hormone production and higher muscle mass are outweighed by the negative side effects on the PBMC telomeres. For reference, I do approximately 60 minutes of cardio (130-140 HR bike, some hard sprints) and 30 minutes of weightlifting daily in the evenings, with an additional 5-6 mile run (155-180 HR) on sat/sun mornings. I am never really “wiped out” by any of my workouts, but I definitely try to lift to the point where my muscles are worked hard, and need rest to regain their strength. It’s hard to define very heavy – compared to a sedentary office drone I can lift a lot, but I do not even bench press my own weight as a regular set.

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  18. Titanovo says:

    Hi James/Vince.

    Interested to get in touch — leaving a comment seemed to be the only way I could find to. I’m reaching out because Titanovo offers a telomere length test, and I really would love to share information about it with your readers who may be interested. I would be happy to discuss our technology in more depth with you over email or phone. Read more here:
    http://titanovo.com/telomere-length-testing/
    Thanks!

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