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In search for the fountain of youth

comment by Nicolle Kraenkel, EAPC Secretary

Rehabilitation and Sports Cardiology


Exercise training is a powerful tool for prevention and rehabilitation of cardiovascular and metabolic diseases. A number of biological mechanisms are addressed to varying degrees by differential exercise modalities – frequency, intensity, type, duration. Most of us therefore believe that by fine-tuning exercise modalities we can tailor exercise protocols to each patient´s specific needs - therapy targets, main risk factors, underlying disease, maybe even to genetically conferred risk.

One of the biological mechanisms that has been studied as a potential target of physical exercise is the shortening of telomeres which normally occurs during cell division in terminally differentiated somatic cells – a mechanism conferring cellular dysfunction during aging. Accelerated telomere shortening has been reported for various chronic pathological conditions and is associated with increased cardiovascular risk [1]. A number of studies have provided associations between habitual physical activity and telomere length, with an apparent dose-response relationship between the amount of regular physical activity and telomere length [2, 3]. Although these observational data are suggestive, associations were mainly between baseline telomere length and self-reported physical activity status. Follow-up measurements 10 years later, or interventional studies have not been able to confirm a causal effect of exercise on telomere length so far [4-7].

In their recent interventional study, Werner et al. investigate whether a 6-month exercise programme employing differential exercise modalities - resistance exercise, moderate continuous or high-intensity interval endurance training - differentially affect telomerase activity and telomere length in various types of leukocytes [8]. They report that telomere length was indeed increased in lymphocytes and granulocytes of healthy individuals participating in an endurance exercise programme (either moderate-intensity continuous training or high-intensity interval training) [8]. In contrast, performing resistance training for 6 months did not result in telomere elongation [8]. In addition, the acute effects of endurance and resistance exercise on telomerase activity in the same individuals were compared and the impact of a marathon race on telomerase activity in athletes was assessed [8].

The study supports application of endurance exercise rather than resistance exercise for the protection of telomere length – at least in healthy individuals. It would be relevant to understand whether the same can be observed in patients with established cardiovascular or metabolic diseases, such as diabetes.

Several potential mechanisms linking physical activity, cardiovascular disease state and telomere length have been discussed in the field in the last 15 years, including inflammation, oxidative stress and stress hormones [3, 9]. Cellular energy sensors, such as AMPK and sirtuins might provide another mechanism linking exercise type and intensity to telomerase activity [10-12]. Werner et al. excluded a role of stress hormones for telomerase activity in their setting and suggested an association with nitric oxide synthase expression [8]. A connexion between NO synthesis and cellular senescence has been discussed for endothelium and leukocytes before, albeit causality is unclear and both effects might rather be downstream of a common signalling process.

Werner et al. have observed that an acute bout of endurance exercise increased telomerase activity, albeit with wide inter-individual variation [8]. This appears to be at variance with earlier studies at first glance [13]. Experimental design may explain most of the differences. In addition, the wide variation of effect in the recent study indicates inter-individual and/or inter-experimental differences. Moreover, telomerase activity might not necessarily translate into measurable telomere lengthening, thus underlining the importance of experimental design.

In conclusion, the study by Werner et al. adds to the notion that endurance exercise rather than resistance exercise may protect telomere erosion in healthy adults, with no difference between moderate or high exercise intensity observed. Future studies need to verify these observations in patients with cardiovascular and metabolic diseases.

 

Note: The content of this article reflects the personal opinion of the author and is not necessarily the official position of the European Society of Cardiology. 

References

Nicolle Kraenkel commented on this article:

Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study
Werner CM et al. Eur H J. 2018 Doi:10.1093/eurheartj/ehy585

Additional References:

  1. Willeit P, Willeit J, Brandstatter A, Ehrlenbach S, Mayr A, Gasperi A, Weger S, Oberhollenzer F, Reindl M, Kronenberg F, Kiechl S. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2010 Aug;30(8):1649-56.
  2. Cherkas LF, Hunkin JL, Kato BS, Richards JB, Gardner JP, Surdulescu GL, Kimura M, Lu X, Spector TD, Aviv A. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008; 168: 154-158.
  3. Arsenis NC, You T, Ogawa EF, Tinsley GM, Zuo L. Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget. 2017 Jul 4;8(27):45008-45019.
  4. Weischer M, Bojesen SE, Nordestgaard BG. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genet. 2014; 10: e1004191.
  5. Shin YA, Lee JH, Song W, Jun TW. Exercise training improves the antioxidant enzyme activity with no changes of telomere length. Mech Ageing Dev. 2008; 129: 254-260.
  6. Mason C, Risques RA, Xiao L, Duggan CR, Imayama I, Campbell KL, Kong A, Foster-Schubert KE, Wang CY, Alfano CM, Blackburn GL, Rabinovitch PS, McTiernan A. Independent and combined effects of dietary weight loss and exercise on leukocyte telomere length in postmenopausal women. Obesity (Silver Spring). 2013; 21: E549-554.
  7. Sjögren P, Fisher R, Kallings L, Svenson U, Roos G, Hellenius ML. Stand up for health--avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people. Br J Sports Med. 2014; 48: 1407-1409.
  8. Werner CM, Hecksteden A, Morsch A, Zundler J, Wegmann M, Kratzsch J, Thiery J, Hohl M, Bittenbring JT, Neumann F, Böhm M, Meyer T, Laufs U. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study. Eur Heart J. 2019 Jan 1;40(1):34-46.
  9. Epel ES, Lin J, Wilhelm FH, Wolkowitz OM, Cawthon R, Adler NE, Dolbier C, Mendes WB, Blackburn EH. Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology. 2006 Apr;31(3):277-87.
  10. Narala SR, Allsopp RC, Wells TB, Zhang G, Prasad P, Coussens MJ, Rossi DJ, Weissman IL, Vaziri H. SIRT1 acts as a nutrient-sensitive growth suppressor and its loss is associated with increased AMPK and telomerase activity. Mol Biol Cell. 2008 Mar;19(3):1210-9.
  11. Nielsen JN1, Mustard KJ, Graham DA, Yu H, MacDonald CS, Pilegaard H, Goodyear LJ, Hardie DG, Richter EA, Wojtaszewski JF. 5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle. J Appl Physiol (1985). 2003 Feb;94(2):631-41.
  12. Wojtaszewski JF1, Birk JB, Frøsig C, Holten M, Pilegaard H, Dela F. 5'AMP activated protein kinase expression in human skeletal muscle: effects of strength training and type 2 diabetes. J Physiol. 2005 Apr 15;564(Pt 2):563-73.
  13. Bruunsgaard H, Jensen MS, Schjerling P, Halkjaer-Kristensen J, Ogawa K, Skinhoj P, Pedersen BK. Exercise induces recruitment of lymphocytes with an activated phenotype and short telomeres in young and elderly humans. Life Sci. 1999; 65: 2623-2633.