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Telomeres – Should you Measure Yours with TeloMe?

Posted: Tue, March 26, 2013 | By:



by Winslow Strong

The last several months have seen an explosion of direct-to-consumer medical tests. We had Talking20 launch DIY blood-tests (my review of the testing experience), uBiome and American Gut (now in phase II for international participation) allow us to catalog the bacterial populations of our gut and other locations, and the already well-established 23andMe drop their price to $99 for a partial sequencing and risk profile of our genomes. The latest service is from TeloMe, inc, offering to measure the length of our telomeres via their Indiegogo campaign.  

This essay was originally posted on Winslow’s blog, BioHackYourself, HERE

Background on telomeres

Telomeres are often analogized to the plastic caps on the ends of shoelaces that help keep them from fraying.  Similarly, our telomeres are caps of repeated non-coding DNA sequences that help maintain chromosomal stability.  They also play an important role in gene regulation.

When a cell divides, its telomeres tend to shorten, unless the enzyme telomerase is present, which is able to preserve and even extend telomeres.  However, telomerase is normally only turned on in cells intended for many divisions – reproductive, stem, blood, and skin – or in cancer cells.  When a cell’s telomeres become very short, it will no longer divide, a point called the Hayflick limit.  This is a potential problem, depending on the tissue, as your body needs cell division for basic bodily repair, wound healing, and sufficient immune response to pathogens.  Most cells in humans reach their Hayflick limit after 30-80 divisions. [1]

Biomarker for aging

Telomere length (TL) has been found to add information to chronological age (how old you are) in predicting many forms of age-related degeneration and mortality in humans.[2] However, it’s clear that TL is not a sufficient predictor on its own, as mere chronological age itself is a much better predictor in the majority of studies.  Furthermore, counterintuitively, TL tends to lose its predictive power as you age.[3]  Some studies suggest that the fraction of “very short” telomeres, or the rate of increase in this fraction, is a superior indicator of aging than the average length or rate.[4]

TL is often hyped as a stand-alone proxy for biological age - your effective age accounting for cognitive and physiological function.  However, this is clearly not true, as chronological age adds significant predictive power to metrics of physical and mental youthfulness beyond TL alone.[5] Some have proposed that TL is better viewed as a biomarker for somatic redundancy – the body’s ability to rebound after insults, such as wounds or infections, since somatic cell replication is key to this resiliency. [6]

Elizabeth Blackburn received the 2009 Nobel Prize in Physiology or Medicine for “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase” She summarized their status as a health prognosticator thusly:

“Telomere shortness is associated with just about all the major diseases of aging… from cardiovascular disease, death from cardiovascular disease, risks of cardiovascular disease, diabetes, diabetes risks such as insulin resistance, vascular dementia, to osteoarthritis…The list goes on and on and the correlation is always in the same direction: shorter telomere length is associated with more disease. The association is absolutely solid now because it has been found in so many cohorts that it cannot be a statistical accident.”[7]

Cause of aging?

It pretty clear that telomere shortening must play a causative role in immunosenescence – the reduced functionality of the immune system with age – via the Hayflick limit. But it’s not entirely clear whether it’s causative of other aspects of aging that it correlates with.  An alternative theory is that TL is merely a secondary biomarker of mitochondrial oxidative damage.[8][9]

However, these distinctions are a bit academic for our present concerns, as telomerase activation seems to ameliorate both mitochondrial function and telomere length, taking care of either possibility.[10][11]

Some evidence regarding the relationship between telomeres, telomerase and aging:

  • Taking typical human cells and growing them in a petri dish will result in short telomeres and no further cell divison after the Hayflick limit is reached.  Adding telomerase to these same cells results in immortal cell lines that can divide indefinitely.  
  • Cancer cells that divide indefinitely require some means of keeping their telomeres long, and in practice that is usually achieved via a mutation to activate telomerase.
  • Dyskeratosis congenita (DKC) is a disease displaying many symptoms of premature aging.  It is believed that inability to maintain telomeres due to mutated telomerase is a major cause of the symptoms.  Stem cell treatment resulting in functional telomerase alleviates many of the symptoms.
  • Researchers intentionally mutated the gene for telomerase in some mice, making it non-functional.  These mice aged rapidly and died young.  Adding normal telomerase back to the same mice restored much of their youthfulness.
  • There’s strong circumstantial evidence from human prostate cancer that short telomeres play an important role in the progression of that disease.[13]

Actionability

When I consider spending the time and money to have a test done, I generally require that information I might discover from it would be potentially actionable, either now or in the foreseeable future, and furthermore that those actions have at least a moderate expected positive impact on my life. 

Interventions backed by correlative evidence

So what actions could be taken if your TL test shows that you have shorter telomeres than you would like?  There is a long list of practices that have been shown to correlate with longer telomere length in observational studies in humans.  These practices largely overlap with generally healthy practices that have been known to at least correlate and in some cases cause greater health in other ways.

Interventions backed by causative evidence

  • Endurance exercise has been strongly linked to longer telomeres in leukocytes (white blood cells) in humans.[14][15]
  • Smoking and alcohol cessation –  Smoking has been found to have dose-dependent adverse correlation with TL.[16] Leukocyte TL didn’t have a statistically significant correlation to alcohol consumption in one study.[17] However, among a population of heavy drinkers, quite a large correlation was observed in another study, along with dose-dependence.[18] A quite large (100k persons) study reported statistically significant adverse correlations of both alcohol and smoking with TL.[19]
  • Multivitamins, particularly vits C and E correlate with greater leukocyte TL.[20]
  • Stress reduction.  Signs of chronic stress correlate with shorter telomeres.[21] As does childhood abuse and neglect.[22]

There are a few more items that have some evidence for directly causing an impact on TL:

There are a few more items that have some evidence for directly causing an impact on TL:

Another longevity research company, Sierra Sciences, focuses on telomere-enhancement and is an apparent competitor to T.A. Science. They claim to have independently verified the effectiveness of TA-65® along with at least 4 other “weak” telomerase activators.[34] Sierra also claims to have “a close working relationship” with T.A. Sciences, and a Scientific American article [35] describes Sierra as a “client” of T.A.[36]

  • Meditation and Qigong interventions have been shown to increase telomerase expression. [23][24]
  • Caloric restriction in mammals has been shown to reduce the rate of telomere shortening and increase life- and health-spans. Interestingly, the mechanism is not via activation of telomerase.[25]  This effect was enhanced in mice engineered to be cancer-resistance by further genetic manipulation to turn on telomerase.[26]
  • Exercise in mice – Mice given a wheel to voluntarily exercise on had higher leukocyte telomerase levels after 3 weeks than those who were denied a wheel.[27][28]
  • TA-65® is a proprietary supplement developed by T.A. Sciences. It is distilled from the roots of the Chinese medicinal plant astragalus membranaceus.   There have been preliminary trials suggesting that TA-65® is efficacious at both activating telomerase and leading to fewer cells with very short telomeres.  The evidence is: in vitro human cell lines;[29] via oral supplementation in mice resulting in a reduced fraction of short telomeres and extended healthspan, but neither extended mean nor maximum life, and no elevation in cancer occurrences;[30] and in vivo in humans via oral dosing as part of a broader supplementation plan resulting in a reduced fraction of short telomeres and favorable changes in T-cells and natural killer cells, especially in those who tested positive for cytomegalovirus.[31]  For a critical appraisal of the aforementioned study, see Suppversity. However, all of the studies that I have been able to find have authors with heavy conflicts of interest – many either affiliated with T.A. Sciences or with with other companies that sell TA-65®. In fact, Calvin Harley, one of the founders of TeloMe Health, inc (a separate company from TeloMe, inc), is also one of the inventors of TA-65®, and claims to take it regularly, as apparently everyone over 40 does at T.A. Sciences.[32][33]

    While the prospect of a supplement that can keep telomeres long is too important to ignore, it should go without saying that there is need for 3rd party confirmation of this finding.  At the time of this writing, TA-65® is very expensive.   

Future

Looking ahead to the future, we should expect the successful gene-therapeutic approaches to telomerase activation in mice to eventually make their way to humans.  Recently, these techniques have yielded very exciting results:  middle- and old-aged mice that were not pre-engineered to be cancer-resistant were delivered a single gene therapy treatment via viral vector.  They experienced statistically significant health- and life-span increases, the latter of 24% and 13% in the middle- and old-aged mice, respectively.[37] These mice did not have a statistically significant excess of cancer, in contrast to past experiments where similar genetic changes were put in place at an embryonic stage.

TeloMe

The company

TeloMe, inc is not a brand new startup pushing a prototype product on Indiegogo.  It was founded in 2010 and currently measures telomeres for the Personal Genome Project, a big Harvard-run study to map genomes of Americans and track changes and health outcomes over time.

The service

The test that TeloMe provides is proprietary. They describe it as: “Our standard test is very much like a standard slot/dot blot, which is among the most accurate of all current telomere analysis methods.”[38]  I don’t have the expertise to evaluate the technical merits of this test, but I take it as a good sign of quality that TeloMe is the company that measures telomeres for the Personal Genome Project.

Saliva rather than blood – Instead of a blood test that is commonly used to obtain leukocyte telomeres, TeloMe will measure and report the average telomere length of all cells found in your saliva. [39]  It turns out that leukocytes (white blood cells) can be extracted from saliva, so at least some of these will contribute to your TL reported by TeloMe. [40]  

This is important since leukocyte TL is one of the more studied TLs, and appears to be one of the more important ones.  One reason for this is that if your leukocytes can’t divide very many times, then the strength and rapidity of your immune response to pathogens will be diminished.[41]  This mechanism been implicated as a major indirect cause of death in the elderly who succumb to pathogenic infections that a younger person would probably shrug off.[42]

Worldwide - TeloMe will ship to most countries in the world, for a $15 extra shipping fee if outside of the US.  Note that you may additionally be charged import fees and VAT, depending on where you live.

Details - TeloMe will measure your telomeres regardless of whether it meets its funding target on Indiegogo.  They are not relying on this for funding, as they already have funding by providing tests to the Personal Genome Project.  Their Indiegogo campaign expires on April 29, along with the discounted rates.  You can expect your saliva collection kit to be delivered in May of 2013.

Weighing the benefits

I purchased TeloMe’s service because I would like to have my telomere length as one of the biomarkers in my “health dashboard.”  The likelihood that in the near future telomerase therapy will be an option, [43] and the near certainty that in its early days it will carry risks associated with it, [44] means that the better the data I have on my risk profile via my telomere length, the better decision I can make on the risk/return of telomerase therapy.  

Whether the service is worth the price depends on how much money you have available to spend on such things.  If the $89 price tag is not steep for you, then I would suggest monitoring this biomarker.  If money is tighter, then I wouldn’t put this near the top of the list for health expenditures.  I would take care of the basics of diet, exercise, activity, sleep, and stress, before getting into genetic testing.  And if you want to get genetic tests, then I suggest starting with 23andMe sequencing for about the same price, as it has the possibility of alerting you to serious genetic issues that are highly actionable, such as familial hypercholesterolemia and a genetic predisposition towards hemochromatosis.

If money were no object, I myself would get the $499 measurement that gives you the distribution, not merely the average, of telomere length of the cells in your saliva.  The added benefit of this measure is that in several studies the proportion of very short telomeres has scored better as a predictor of mortality and aging than the average length. [45]

Another point to keep in mind is that the value of measuring your telomeres at several time points may far outweigh the value of a single measurement.  For example, it would allow you to estimate the rate of telomere shortening.  We still await larger prospective cohort studies of to guide usage of information of this type.  The data that TeloMe generates will be studied (with your consent) in the Personal Genome Project to help yield just that.  So by participating in this service, you also help advance our understanding of telomeres and their role in human health.

Help support Biohack Yourself: If you would like to purchase the TeloMe service and found this review to be helpful, then you can help support Biohack Yourself by purchasing through our affiliate link.  You get the same price, and this allows me to dedicate more time to future articles like this.

EDITS: An earlier version of this article mistakenly identified TeloMe, Inc, the provider of the direct-to-consumer telomere testing being discussed here, with a different company, TeloMe Health, Inc.  Apologies for that mistake. 

Acknowledgements

I uncovered many of the studies for this post on the blogs: Fight Aging!, Sam Snyder, and Suppversity.  Thanks to them for all their great work.

Disclaimer: The information presented on this site is not medical advice, and should not be construed as a substitute for medical care or clinical testing.  Any content or services offered by Biohack Yourself and it’s authors is not intended to constitute, or substitute for, the practice of medicine, or a clinical or healthcare diagnosis.

Notes:

  1. TELOMERES AND TELOMERASE. The American Federation for Aging Research. 2011
  2. Der, Geoff, et al. “Is Telomere Length a Biomarker for Aging: Cross-Sectional Evidence from the West of Scotland?.” PLOS ONE 7.9 (2012): e45166.
  3. Boonekamp, Jelle J., et al. “Telomere length behaves as biomarker of somatic redundancy rather than biological age.” Aging cell (2013).
  4. Vera, Elsa, et al. “The rate of increase of short telomeres predicts longevity in mammals.” Cell Reports (2012).
  5. Der, Geoff, et al. “Is Telomere Length a Biomarker for Aging: Cross-Sectional Evidence from the West of Scotland?.” PLOS ONE 7.9 (2012): e45166.
  6. Boonekamp, Jelle J., et al. “Telomere length behaves as biomarker of somatic redundancy rather than biological age.” Aging cell (2013).
  7. http://www.svhi.com/newsletters/2011/slf-081811.pdf
  8. Linking Telomere Shortening and Mitochondrial Damage?” Fight Aging!  2007.
  9. More On Telomere Shortening and Mitochondrial Dysfunction” Fight Aging! 2008.
  10. Ahmed, Shaheda, et al. “Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress.” Journal of cell science 121.7 (2008): 1046-1053.
  11. Pérez-Rivero, Gema, et al. “Telomerase deficiency promotes oxidative stress by reducing catalase activity.” Free Radical Biology and Medicine 45.9 (2008): 1243-1251.
  12. Jaskelioff, Mariela, et al. “Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice.” Nature 469.7328 (2010): 102-106. Summary
  13. Meeker, Alan K. “Telomeres and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology.” Urologic Oncology: Seminars and Original Investigations. Vol. 24. No. 2. Elsevier, 2006.
  14. Werner, Christian, et al. “Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall.“ Circulation 120.24 (2009): 2438-2447.
  15. Du, Mengmeng, et al. “Physical activity, sedentary behavior, and leukocyte telomere length in women.“ American journal of epidemiology 175.5 (2012): 414-422.
  16. Valdes, A. M., et al. “Obesity, cigarette smoking, and telomere length in women.” The Lancet 366.9486 (2005): 662-664.
  17. Bekaert, Sofie, et al. “Telomere length and cardiovascular risk factors in a middle‐aged population free of overt cardiovascular disease.“ Aging cell 6.5 (2007): 639-647.
  18. Pavanello, Sofia, et al. “Shortened telomeres in individuals with abuse in alcohol consumption.” International journal of cancer 129.4 (2011): 983-992.
  19. Significant relationship between mortality and telomere length discovered.” Eureka Alert. 2012.
  20. Qun Xu, Christine G Parks, Lisa A DeRoo, Richard M Cawthon, Dale P Sandler and Honglei Chen. “Multivitamin use and telomere length in women.” Am J Clin Nutr  2009 June  89: 1857-1863, 2009.
  21. Parks, Christine G., et al. “Telomere length, current perceived stress, and urinary stress hormones in women.“ Cancer Epidemiology Biomarkers & Prevention 18.2 (2009): 551-560.Summarized
  22. Tyrka, Audrey R., et al. “Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging.” Biological psychiatry 67.6 (2010): 531-534.
  23. Jacobs, Tonya L., et al. “Intensive meditation training, immune cell telomerase activity, and psychological mediators.” Psychoneuroendocrinology 36.5 (2011): 664-681.
  24. Ho, Rainbow TH, et al. “A Randomized Controlled Trial of Qigong Exercise on Fatigue Symptoms, Functioning, and Telomerase Activity in Persons with Chronic Fatigue or Chronic Fatigue Syndrome.” Annals of Behavioral Medicine (2012): 1-11.
  25. Shackelford, Rodney. “Telomeres, Telomerase and Aging.” h+ Magazine. 2011.
  26. Vera, Elsa, et al. “Telomerase Reverse Transcriptase Synergizes with Calorie Restriction to Increase Health Span and Extend Mouse Longevity.” PloS one 8.1 (2013): e53760.
  27. Werner, Christian, et al. “Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall.“ Circulation 120.24 (2009): 2438-2447.
  28. Du, Mengmeng, et al. “Physical activity, sedentary behavior, and leukocyte telomere length in women.“ American journal of epidemiology 175.5 (2012): 414-422.
  29. Molgora, Brenda, et al. “Functional Assessment of Pharmacological Telomerase Activators in Human T Cells.” Cells 2.1 (2013): 57-66.
  30. de Jesus, Bruno Bernardes, et al. “The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence.” Aging cell 10.4 (2011): 604-621.
  31. Harley, Calvin B., et al. “A natural product telomerase activator as part of a health maintenance program.” Rejuvenation research 14.1 (2011): 45-56.
  32. see the “Author Disclosure Statement” of: Harley, Calvin B., et al. “A natural product telomerase activator as part of a health maintenance program.” Rejuvenation research 14.1 (2011): 45-56.
  33. Kendrick, Mandy. “Anti-aging pill targets telomeres at the ends of chromosomes.” Scientific American 17 (2009).
  34. http://www.sierrasci.com/research/index.html March 24, 2013.
  35. Kendrick, Mandy. “Anti-aging pill targets telomeres at the ends of chromosomes.” Scientific American 17 (2009).
  36. http://www.sierrasci.com/newsletter/newsletter2.html. March 24, 2013.
  37. Bernardes de Jesus, Bruno, et al. “Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.” EMBO Molecular Medicine (2012).
  38. Personal communication
  39. Personal communication
  40. Vidović, Anđelko, et al. “Determination of leucocyte subsets in human saliva by flow cytometry.” Archives of Oral Biology (2011).
  41. Reed, John R., et al. “Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo.” The Journal of experimental medicine 199.10 (2004): 1433-1443.
  42. Fossel, Michael. “Reversing human aging.” The Science of Anti-Aging Medicine(2003): 7.
  43. de Jesus, Bruno Bernardes, and Maria A. Blasco. “Potential of telomerase activation in extending health span and longevity.” Current opinion in cell biology (2012).
  44. Rae, Michael. “Tale of Telomerase: Lessons and Limits in a Late-Life Launch.” SENS Research Foundation
  45. Vera, Elsa, et al. “The rate of increase of short telomeres predicts longevity in mammals.” Cell Reports (2012).


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