Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?

Abstract

Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=−0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.

Key words

aging - running - sirtuins - anti-aging - lifelong exercise

Publication History

Received: 09 March 2021

Accepted: 02 May 2021

Article published online:
13 July 2021

• References

• 1 Amano H, Chaudhury A, Rodriguez-Aguayo C. et al. Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease. Cell Metab 2019; 29: 1274-1290
• 2 Liang F, Kume S, Koya D. SIRT1 and insulin resistance. Nat Rev Endocrinol 2009; 5: 367
• 3 Sahin E, DePinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 2010; 464: 520-528
• 4 Blackburn EH, Epel ES, Lin J. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science 2015; 350: 1193-1198
• 5 Blackburn EH. Structure and function of telomeres. Nature 1991; 350: 569-573
• 6 de Lange T. Shelterin-mediated telomere protection. Annu Rev Genet 2018; 52: 223-247
• 7 Wang J, Dong X, Cao L. et al. Association between telomere length and diabetes mellitus: A meta-analysis. J Int Med Res 2016; 44: 1156-1173
• 8 Pieters N, Janssen BG, Valeri L. et al. Molecular responses in the telomere-mitochondrial axis of ageing in the elderly: A candidate gene approach. Mech Ageing Dev 2015; 145: 51-57
• 9 Rahman S, Islam R. Mammalian Sirt1: Insights on its biological functions. Cell Commun Signal 2011; 9: 1-8
• 10 Pucci B, Villanova L, Sansone L. et al. Sirtuins: The molecular basis of beneficial effects of physical activity. Intern Emerg Med 2013; 8: 23-25
• 11 Thirupathi A, De Souza CT. Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise. J Physiol Biochem 2017; 73: 487-494
• 12 Vargas-Ortiz K, Pérez-Vázquez V, Macías-Cervantes MH. Exercise and sirtuins: A way to mitochondrial health in skeletal muscle. Int J Mol Sci 2019; 20: 2717
• 13 Cantó C, Jiang LQ, Deshmukh AS. et al. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell metab 2010; 11: 213-219
• 14 Aguiar SS, Rosa TS, Sousa CV. et al. Influence of body fat on oxidative stress and telomere length of master athletes. J Strength Cond Res 2021; 35: 1693–1699. doi:10.1519/JSC.0000000000002932
• 15 Rosa TS, Neves RVP, Deus LA. et al. Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes. Nitric Oxide 2020; 102: 42-51
• 16 Korhonen MT, Haverinen M, Degens H. Training and nutritional needs. In: Reaburn PRJ. Nutrition Performance in Masters Athletes. Boca Raton: CRC Press; 2014: 291-315
• 17 Kusy K, Zielinski J. Sprinters versus long-distance runners: how to grow old healthy. Exerc Sport Sci Rev 2015; 43: 57-64
• 18 Koltai E, Bori Z, Osvath P. et al. Master athletes have higher miR-7, SIRT3 and SOD2 expression in skeletal muscle than age-matched sedentary controls. Redox biol 2018; 19: 46-51
• 19 Kusy K, Zieliński J, Pilaczyńska-Szcześniak Ł. Insulin sensitivity and β-cell function estimated by HOMA2 model in sprint-trained athletes aged 20−90 years vs endurance runners and untrained participants. J Sports Sci 2013; 31: 1656-1664
• 20 Harriss D, MacSween A, Atkinson G. Ethical standards in sport and exercise science research: 2020 update. Int J Sports Med 2019; 40: 813-817
• 21 Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002; 30: e47-e47
• 22 Simoes HG, Sousa CV, dos Santos Rosa T. et al. Longer telomere length in elite master sprinters: Relationship to performance and body composition. Int J Sports Med 2017; 38: 1111-1116
• 23 Cohen J. Statistical Power Analysis for the Behavioral Sciences. Cambridge: Academic press; 2013
• 24 Aguiar SS, Sousa CV, Deus LA. et al. Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay. Exp Gerontol 2020; 130: 110806
• 25 Kim Y, Triolo M, Hood DA. Impact of aging and exercise on mitochondrial quality control in skeletal muscle. Oxid Med Cell Longev 2017; 2017: 3165396
• 26 Escobar KA, Cole NH, Mermier CM. et al. Autophagy and aging: Maintaining the proteome through exercise and caloric restriction. Aging cell 2019; 18: e12876
• 27 Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med 2016; 48: e245-e245
• 28 Ruderman NB, Xu XJ, Nelson L. et al. AMPK and SIRT1: A long-standing partnership?. Am J Physiol Endocrinol Metab 2010; 4: e751-e760
• 29 Cao Y, Jiang X, Ma H. et al. SIRT1 and insulin resistance. J Diabetes Complications 2016; 30: 178-183
• 30 Prud’homme GJ, Glinka Y, Udovyk O. et al. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun 2014; 452: 649-654
• 31 Aguiar SS, Sousa CV, Santos PA. et al. Master athletes have longer telomeres than age-matched non-athletes. A systematic review, meta-analysis and discussion of possible mechanisms. Exp Gerontol 2021; 146: 111212
• 32 Sousa CV, Aguiar SS, Santos PA. et al. Telomere length and redox balance in master endurance runners: The role of nitric oxide. Exp Gerontol 2019; 117: 113-118
• 33 Kim S, Bi X, Czarny-Ratajczak M. et al. Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity. Biogerontology 2012; 13: 119-131
• 34 Dimauro I, Scalabrin M, Fantini C. et al. Resistance training and redox homeostasis: Correlation with age-associated genomic changes. Redox biol 2016; 10: 34-44
• 35 Jeong J, Juhn K, Lee H. et al. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp Mol Med 2007; 39: 8-13