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Telomere Length Maintenance and Cardio-Metabolic Disease Prevention Through Exercise Training

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Abstract

Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason telomere length is a marker of biological age. Abnormally short telomeres may culminate in the manifestation of a number of cardio-metabolic diseases. Age-related cardio-metabolic diseases attributable to an inactive lifestyle, such as obesity, type 2 diabetes mellitus and cardiovascular disease, are associated with short leukocyte telomeres. Exercise training prevents and manages the symptoms of many cardio-metabolic diseases whilst concurrently maintaining telomere length. The positive relationship between exercise training, physical fitness and telomere length raises the possibility of a mediating role of telomeres in chronic disease prevention via exercise. Further elucidation of the underpinning molecular mechanisms of how exercise maintains telomere length should provide crucial information on how physical activity can be best structured to combat the chronic disease epidemic and improve the human health span. Here, we synthesise and discuss the current evidence on the impact of physical activity and cardiorespiratory fitness on telomere dynamics. We provide the molecular mechanisms with a known role in exercise-induced telomere length maintenance and highlight unexplored, alternative pathways ripe for future investigations.

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References

  1. Blackburn EH. Structure and function of telomeres. Nature. 1991;350(6319):569–73.

    Article  CAS  PubMed  Google Scholar 

  2. Blackburn EH. Switching and signaling at the telomere. Cell. 2001;106(6):661–73.

    Article  CAS  PubMed  Google Scholar 

  3. Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279(5349):349–52.

    Article  CAS  PubMed  Google Scholar 

  4. Daniali L, Benetos A, Susser E, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun. 2013;4:1597.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Brouilette S, Singh RK, Thompson JR, et al. White cell telomere length and risk of premature myocardial infarction. Arterioscler Thromb Vasc Biol. 2003;23(5):842–6.

    Article  CAS  PubMed  Google Scholar 

  6. Samani NJ, Boultby R, Butler R, et al. Telomere shortening in atherosclerosis. Lancet. 2001;358(9280):472–3.

    Article  CAS  PubMed  Google Scholar 

  7. Mainous AG 3rd, Codd V, Diaz VA, et al. Leukocyte telomere length and coronary artery calcification. Atherosclerosis. 2010;210(1):262–7.

    Article  CAS  PubMed  Google Scholar 

  8. Zee RY, Castonguay AJ, Barton NS, et al. Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study. Transl Res. 2010;155(4):166–9.

    Article  CAS  PubMed  Google Scholar 

  9. Salpea KD, Talmud PJ, Cooper JA, et al. Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis. 2010;209(1):42–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ma H, Zhou Z, Wei S, et al. Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS One. 2011;6(6):e20466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Epel ES, Blackburn EH, Lin J, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA. 2004;101(49):17312–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Puterman E, Lin J, Krauss J, et al. Determinants of telomere attrition over 1 year in healthy older women: stress and health behaviors matter. Mol Psychiatry. 2014;20(4):529–35.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet. 2012;13(10):693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation. 2003;107(24):3109–16.

    Article  PubMed  Google Scholar 

  15. Sigal RJ, Kenny GP, Wasserman DH, et al. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(6):1433–8.

    Article  PubMed  Google Scholar 

  16. Lemanne D, Cassileth B, Gubili J. The role of physical activity in cancer prevention, treatment, recovery, and survivorship. Oncology (Williston Park). 2013;27(6):580–5.

    PubMed  Google Scholar 

  17. Moyzis RK, Buckingham JM, Cram LS, et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA. 1988;85(18):6622–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen W, Kimura M, Kim S, et al. Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule. J Gerontol A Biol Sci Med Sci. 2011;66(3):312–9.

    Article  CAS  PubMed  Google Scholar 

  19. Verdun RE, Karlseder J. Replication and protection of telomeres. Nature. 2007;447(7147):924–31.

    Article  CAS  PubMed  Google Scholar 

  20. Oikawa S, Kawanishi S. Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett. 1999;453(3):365–8.

    Article  CAS  PubMed  Google Scholar 

  21. Kawanishi S, Oikawa S. Mechanism of telomere shortening by oxidative stress. Ann N Y Acad Sci. 2004;1019:278–84.

    Article  CAS  PubMed  Google Scholar 

  22. von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002;27(7):339–44.

    Article  Google Scholar 

  23. Herbig U, Jobling WA, Chen BP, et al. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14(4):501–13.

    Article  CAS  PubMed  Google Scholar 

  24. de Lange T. How shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol. 2010;75:167–77.

    Article  PubMed  Google Scholar 

  25. Chin L, Artandi SE, Shen Q, et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97(4):527–38.

    Article  CAS  PubMed  Google Scholar 

  26. Nandakumar J, Cech TR. Finding the end: recruitment of telomerase to telomeres. Nat Rev Mol Cell Biol. 2013;14(2):69–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Griffith JD, Comeau L, Rosenfield S, et al. Mammalian telomeres end in a large duplex loop. Cell. 1999;97(4):503–14.

    Article  CAS  PubMed  Google Scholar 

  28. Broccoli D, Smogorzewska A, Chong L, et al. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 1997;17(2):231–5.

    Article  CAS  PubMed  Google Scholar 

  29. Takai KK, Hooper S, Blackwood S, et al. In vivo stoichiometry of shelterin components. J Biol Chem. 2010;285(2):1457–67.

    Article  CAS  PubMed  Google Scholar 

  30. van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997;385(6618):740–3.

    Article  PubMed  Google Scholar 

  31. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998;92(3):401–13.

    Article  PubMed  Google Scholar 

  32. Kim SH, Beausejour C, Davalos AR, et al. TIN2 mediates functions of TRF2 at human telomeres. J Biol Chem. 2004;279(42):43799–804.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Y, Chen LY, Han X, et al. Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci USA. 2013;110(14):5457–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang F, Podell ER, Zaug AJ, et al. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007;445(7127):506–10.

    Article  CAS  PubMed  Google Scholar 

  35. Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448(7157):1068–71.

    Article  CAS  PubMed  Google Scholar 

  36. Bae NS, Baumann P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell. 2007;26(3):323–34.

    Article  CAS  PubMed  Google Scholar 

  37. Sarthy J, Bae NS, Scrafford J, et al. Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J. 2009;28(21):3390–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Martinez P, Thanasoula M, Carlos AR, et al. Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites. Nat Cell Biol. 2010;12(8):768–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Martinez P, Blasco MA. Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer. 2011;11(3):161–76.

    Article  CAS  PubMed  Google Scholar 

  40. Sfeir A, de Lange T. Removal of shelterin reveals the telomere end-protection problem. Science. 2012;336(6081):593–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. de Lange T. How telomeres solve the end-protection problem. Science. 2009;326(5955):948–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Benetti R, Garcia-Cao M, Blasco MA. Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nat Genet. 2007;39(2):243–50.

    Article  CAS  PubMed  Google Scholar 

  43. Blasco MA. The epigenetic regulation of mammalian telomeres. Nat Rev Genet. 2007;8(4):299–309.

    Article  CAS  PubMed  Google Scholar 

  44. Gonzalo S, Jaco I, Fraga MF, et al. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol. 2006;8(4):416–24.

    Article  CAS  PubMed  Google Scholar 

  45. Redon S, Reichenbach P, Lingner J. The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res. 2010;38(17):5797–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985;43(2 Pt 1):405–13.

    Article  CAS  PubMed  Google Scholar 

  47. Wright WE, Piatyszek MA, Rainey WE, et al. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996;18(2):173–9.

    Article  CAS  PubMed  Google Scholar 

  48. Broccoli D, Young JW, de Lange T. Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci USA. 1995;92(20):9082–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wernig A, Schafer R, Knauf U, et al. On the regenerative capacity of human skeletal muscle. Artif Organs. 2005;29(3):192–8.

    Article  PubMed  Google Scholar 

  50. Chen CH, Chen RJ. Prevalence of telomerase activity in human cancer. J Formos Med Assoc. 2011;110(5):275–89.

    Article  CAS  PubMed  Google Scholar 

  51. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266(5193):2011–5.

    Article  CAS  PubMed  Google Scholar 

  52. Vaziri H, Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol. 1998;8(5):279–82.

    Article  CAS  PubMed  Google Scholar 

  53. Wojtyla A, Gladych M, Rubis B. Human telomerase activity regulation. Mol Biol Rep. 2011;38(5):3339–49.

    Article  CAS  PubMed  Google Scholar 

  54. Smogorzewska A, de Lange T. Regulation of telomerase by telomeric proteins. Annu Rev Biochem. 2004;73:177–208.

    Article  CAS  PubMed  Google Scholar 

  55. Wang F, Lei M. Human telomere POT1-TPP1 complex and its role in telomerase activity regulation. Methods Mol Biol. 2011;735:173–87.

    Article  CAS  PubMed  Google Scholar 

  56. Liu JP, Chen SM, Cong YS, et al. Regulation of telomerase activity by apparently opposing elements. Ageing Res Rev. 2010;9(3):245–56.

    Article  CAS  PubMed  Google Scholar 

  57. Zhou J, Ding D, Wang M, et al. Telomerase reverse transcriptase in the regulation of gene expression. BMB Rep. 2014;47(1):8–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet. 2010;11(5):319–30.

    Article  CAS  PubMed  Google Scholar 

  59. Nabetani A, Ishikawa F. Alternative lengthening of telomeres pathway: recombination-mediated telomere maintenance mechanism in human cells. J Biochem. 2011;149(1):5–14.

    Article  CAS  PubMed  Google Scholar 

  60. Heaphy CM, Subhawong AP, Hong SM, et al. Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol. 2011;179(4):1608–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bojovic B, Booth RE, Jin Y, et al. Alternative lengthening of telomeres in cancer stem cells in vivo. Oncogene. 2014;34:611–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Silvestre DC, Pineda JR, Hoffschir F, et al. Alternative lengthening of telomeres in human glioma stem cells. Stem Cells. 2011;29(3):440–51.

    Article  CAS  PubMed  Google Scholar 

  63. Neumann AA, Watson CM, Noble JR, et al. Alternative lengthening of telomeres in normal mammalian somatic cells. Genes Dev. 2013;27(1):18–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hemann MT, Greider CW. Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res. 2000;28(22):4474–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zijlmans JM, Martens UM, Poon SS, et al. Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats. Proc Natl Acad Sci USA. 1997;94(14):7423–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wright WE, Shay JW. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nat Med. 2000;6(8):849–51.

    Article  CAS  PubMed  Google Scholar 

  67. Vina J, Sanchis-Gomar F, Martinez-Bello V, et al. Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol. 2012;167(1):1–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Warburton DE, Nicol CW, Bredin SS. Health benefits of physical activity: the evidence. CMAJ. 2006;174(6):801–9.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Powell KE, Paluch AE, Blair SN. Physical activity for health: what kind? How much? How intense? On top of what? Annu Rev Public Health. 2011;32:349–65.

    Article  PubMed  Google Scholar 

  70. Shalev I, Entringer S, Wadhwa PD, et al. Stress and telomere biology: a lifespan perspective. Psychoneuroendocrinology. 2013;38(9):1835–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shiels PG, McGlynn LM, MacIntyre A, et al. Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort. PLoS One. 2011;6(7):e22521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nettleton JA, Diez-Roux A, Jenny NS, et al. Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr. 2008;88(5):1405–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Lee M, Martin H, Firpo MA, et al. Inverse association between adiposity and telomere length: the Fels Longitudinal Study. Am J Hum Biol. 2011;23(1):100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Garcia-Calzon S, Gea A, Razquin C, et al. Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: the PREDIMED-NAVARRA trial. Int J Obes (Lond). 2014;38(2):177–82.

    Article  CAS  Google Scholar 

  75. Buxton JL, Das S, Rodriguez A, et al. Multiple measures of adiposity are associated with mean leukocyte telomere length in the northern Finland birth cohort 1966. PLoS One. 2014;9(6):e99133.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Kim S, Parks CG, DeRoo LA, et al. Obesity and weight gain in adulthood and telomere length. Cancer Epidemiol Biomark Prev. 2009;18(3):816–20.

    Article  CAS  Google Scholar 

  77. Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking, and telomere length in women. Lancet. 2005;366(9486):662–4.

    Article  CAS  PubMed  Google Scholar 

  78. Chen S, Yeh F, Lin J, et al. Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study. Aging (Albany NY). 2014;6(5):380–9.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Bekaert S, De Meyer T, Rietzschel ER, et al. Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease. Aging Cell. 2007;6(5):639–47.

    Article  CAS  PubMed  Google Scholar 

  80. Diaz VA, Mainous AG, Player MS, et al. Telomere length and adiposity in a racially diverse sample. Int J Obes (Lond). 2010;34(2):261–5.

    Article  CAS  Google Scholar 

  81. Buxton JL, Walters RG, Visvikis-Siest S, et al. Childhood obesity is associated with shorter leukocyte telomere length. J Clin Endocrinol Metab. 2011;96(5):1500–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Al-Attas OS, Al-Daghri N, Bamakhramah A, et al. Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth. Acta Paediatr. 2010;99(6):896–9.

    Article  CAS  PubMed  Google Scholar 

  83. Nordfjall K, Eliasson M, Stegmayr B, et al. Telomere length is associated with obesity parameters but with a gender difference. Obesity (Silver Spring). 2008;16(12):2682–9.

    Article  PubMed  CAS  Google Scholar 

  84. Garcia-Calzon S, Moleres A, Marcos A, et al. Telomere length as a biomarker for adiposity changes after a multidisciplinary intervention in overweight/obese adolescents: the EVASYON study. PLoS One. 2014;9(2):e89828.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Shen Q, Zhao X, Yu L, et al. Association of leukocyte telomere length with type 2 diabetes in mainland Chinese populations. J Clin Endocrinol Metab. 2012;97(4):1371–4.

    Article  CAS  PubMed  Google Scholar 

  86. Testa R, Olivieri F, Sirolla C, et al. Leukocyte telomere length is associated with complications of type 2 diabetes mellitus. Diabet Med. 2011;28(11):1388–94.

    Article  CAS  PubMed  Google Scholar 

  87. Olivieri F, Lorenzi M, Antonicelli R, et al. Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction. Atherosclerosis. 2009;206(2):588–93.

    Article  CAS  PubMed  Google Scholar 

  88. Sampson MJ, Winterbone MS, Hughes JC, et al. Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care. 2006;29(2):283–9.

    Article  CAS  PubMed  Google Scholar 

  89. Gardner JP, Li S, Srinivasan SR, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation. 2005;111(17):2171–7.

    Article  CAS  PubMed  Google Scholar 

  90. Zhao J, Zhu Y, Lin J, et al. Short leukocyte telomere length predicts risk of diabetes in American Indians: the strong heart family study. Diabetes. 2014;63(1):354–62.

    Article  CAS  PubMed  Google Scholar 

  91. You NC, Chen BH, Song Y, et al. A prospective study of leukocyte telomere length and risk of type 2 diabetes in postmenopausal women. Diabetes. 2012;61(11):2998–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Panayiotou AG, Nicolaides AN, Griffin M, et al. Leukocyte telomere length is associated with measures of subclinical atherosclerosis. Atherosclerosis. 2010;211(1):176–81.

    Article  CAS  PubMed  Google Scholar 

  93. Fitzpatrick AL, Kronmal RA, Gardner JP, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol. 2007;165(1):14–21.

    Article  PubMed  Google Scholar 

  94. Yang Z, Huang X, Jiang H, et al. Short telomeres and prognosis of hypertension in a Chinese population. Hypertension. 2009;53(4):639–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Demissie S, Levy D, Benjamin EJ, et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell. 2006;5(4):325–30.

    Article  CAS  PubMed  Google Scholar 

  96. van der Harst P, van der Steege G, de Boer RA, et al. Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol. 2007;49(13):1459–64.

    Article  PubMed  CAS  Google Scholar 

  97. Willeit P, Willeit J, Brandstatter A, et al. Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2010;30(8):1649–56.

    Article  CAS  PubMed  Google Scholar 

  98. Farzaneh-Far R, Cawthon RM, Na B, et al. Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study. Arterioscler Thromb Vasc Biol. 2008;28(7):1379–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet. 2007;369(9556):107–14.

    Article  CAS  PubMed  Google Scholar 

  100. Haycock PC, Heydon EE, Kaptoge S, et al. Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2014;349:g4227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Zee RY, Castonguay AJ, Barton NS, et al. Relative leukocyte telomere length and risk of incident ischemic stroke in men: a prospective, nested case-control approach. Rejuvenation Res. 2010;13(4):411–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Perez-Rivera JA, Pabon-Osuna P, Cieza-Borrella C, et al. Effect of telomere length on prognosis in men with acute coronary syndrome. Am J Cardiol. 2014;113(3):418–21.

    Article  CAS  PubMed  Google Scholar 

  103. Cawthon RM, Smith KR, O’Brien E, et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361(9355):393–5.

    Article  CAS  PubMed  Google Scholar 

  104. Epel ES, Merkin SS, Cawthon R, et al. The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men. Aging (Albany NY). 2009;1(1):81–8.

    Article  CAS  Google Scholar 

  105. Lee HW, Blasco MA, Gottlieb GJ, et al. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392(6676):569–74.

    Article  CAS  PubMed  Google Scholar 

  106. Herrera E, Samper E, Martin-Caballero J, et al. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 1999;18(11):2950–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Rudolph KL, Chang S, Lee HW, et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. 1999;96(5):701–12.

    Article  CAS  PubMed  Google Scholar 

  108. Perez-Rivero G, Ruiz-Torres MP, Rivas-Elena JV, et al. Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production. Circulation. 2006;114(4):309–17.

    Article  CAS  PubMed  Google Scholar 

  109. Wong KK, Maser RS, Bachoo RM, et al. Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature. 2003;421(6923):643–8.

    Article  CAS  PubMed  Google Scholar 

  110. Chang S, Multani AS, Cabrera NG, et al. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet. 2004;36(8):877–82.

    Article  CAS  PubMed  Google Scholar 

  111. Bhayadia R, Schmidt BM, Melk A, et al. Senescence-induced oxidative stress causes endothelial dysfunction. J Gerontol A Biol Sci Med Sci. 2016;71(2):161–9.

    Article  PubMed  Google Scholar 

  112. Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Li H, Horke S, Forstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis. 2014;237(1):208–19.

    Article  CAS  PubMed  Google Scholar 

  114. Watson JD. Type 2 diabetes as a redox disease. Lancet. 2014;383(9919):841–3.

    Article  PubMed  Google Scholar 

  115. Fredman G, Ozcan L, Tabas I. Common therapeutic targets in cardiometabolic disease. Sci Transl Med. 2014;6(239):239ps5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Salpea KD, Maubaret CG, Kathagen A, et al. The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. PLoS One. 2013;8(9):e73756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kurz DJ, Decary S, Hong Y, et al. Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci. 2004;117(Pt 11):2417–26.

    Article  CAS  PubMed  Google Scholar 

  118. Ottaviani A, Gilson E, Magdinier F. Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie. 2008;90(1):93–107.

    Article  CAS  PubMed  Google Scholar 

  119. Baur JA, Zou Y, Shay JW, et al. Telomere position effect in human cells. Science. 2001;292(5524):2075–7.

    Article  CAS  PubMed  Google Scholar 

  120. Robin JD, Ludlow AT, Batten K, et al. Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances. Genes Dev. 2014;28(22):2464–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Koering CE, Pollice A, Zibella MP, et al. Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. 2002;3(11):1055–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hernandez-Caballero E, Herrera-Gonzalez NE, Salamanca-Gomez F, et al. Role of telomere length in subtelomeric gene expression and its possible relation to cellular senescence. BMB Rep. 2009;42(11):747–51.

    Article  CAS  PubMed  Google Scholar 

  123. Ning Y, Xu JF, Li Y, et al. Telomere length and the expression of natural telomeric genes in human fibroblasts. Hum Mol Genet. 2003;12(11):1329–36.

    Article  CAS  PubMed  Google Scholar 

  124. Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet. 2013;45(4):422–7 (7e1–2).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Masi S, D’Aiuto F, Martin-Ruiz C, et al. Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort. Eur Heart J. 2014;35(46):3296–303.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Baragetti A, Palmen J, Garlaschelli K, et al. Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population. J Intern Med. 2015;277(4):478–87.

    Article  CAS  PubMed  Google Scholar 

  127. Cherkas LF, Hunkin JL, Kato BS, et al. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008;168(2):154–8.

    Article  PubMed  Google Scholar 

  128. Du M, Prescott J, Kraft P, et al. Physical activity, sedentary behavior, and leukocyte telomere length in women. Am J Epidemiol. 2012;175(5):414–22.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Ludlow AT, Zimmerman JB, Witkowski S, et al. Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc. 2008;40(10):1764–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Savela S, Saijonmaa O, Strandberg TE, et al. Physical activity in midlife and telomere length measured in old age. Exp Gerontol. 2013;48(1):81–4.

    Article  CAS  PubMed  Google Scholar 

  131. Song Z, von Figura G, Liu Y, et al. Lifestyle impacts on the aging-associated expression of biomarkers of DNA damage and telomere dysfunction in human blood. Aging Cell. 2010;9(4):607–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Cassidy A, De Vivo I, Liu Y, et al. Associations between diet, lifestyle factors, and telomere length in women. Am J Clin Nutr. 2010;91(5):1273–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Diaz VA, Mainous AG 3rd, Everett CJ, et al. Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium. Am J Cardiol. 2010;106(5):659–63.

    Article  CAS  PubMed  Google Scholar 

  134. Fujishiro K, Diez-Roux AV, Landsbergis PA, et al. Current employment status, occupational category, occupational hazard exposure and job stress in relation to telomere length: the Multiethnic Study of Atherosclerosis (MESA). Occup Environ Med. 2013;70(8):552–60.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Kim JH, Ko JH, Lee DC, et al. Habitual physical exercise has beneficial effects on telomere length in postmenopausal women. Menopause. 2012;19(10):1109–15.

    Article  PubMed  Google Scholar 

  136. Garland SN, Johnson B, Palmer C, et al. Physical activity and telomere length in early stage breast cancer survivors. Breast Cancer Res. 2014;16(4):413.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Loprinzi PD. Leisure-time screen-based sedentary behavior and leukocyte telomere length: implications for a new leisure-time screen-based sedentary behavior mechanism. Mayo Clin Proc. 2015;90(6):786–90.

    Article  CAS  PubMed  Google Scholar 

  138. Sjogren P, Fisher R, Kallings L, et al. 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(19):1407–9.

    Article  PubMed  Google Scholar 

  139. Washburn RA, Smith KW, Jette AM, et al. The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46(2):153–62.

    Article  CAS  PubMed  Google Scholar 

  140. Lee JY, Bang HW, Ko JH, et al. Leukocyte telomere length is independently associated with gait speed in elderly women. Maturitas. 2013;75(2):165–9.

    Article  CAS  PubMed  Google Scholar 

  141. Maeda T, Oyama J, Sasaki M, et al. The physical ability of elderly female Japanese patients with cerebrovascular disease correlates with telomere length in their peripheral blood leukocytes. Aging Clin Exp Res. 2011;23(1):22–8.

    Article  PubMed  Google Scholar 

  142. Maeda T, Oyama J, Higuchi Y, et al. The physical ability of Japanese female elderly with cerebrovascular disease correlates with the telomere length and subtelomeric methylation status in their peripheral blood leukocytes. Gerontology. 2011;57(2):137–43.

    Article  PubMed  Google Scholar 

  143. Bendix L, Gade MM, Staun PW, et al. Leukocyte telomere length and physical ability among Danish twins age 70+. Mech Ageing Dev. 2011;132(11–12):568–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Baylis D, Ntani G, Edwards MH, et al. Inflammation, telomere length, and grip strength: a 10-year longitudinal study. Calcif Tissue Int. 2014;95(1):54–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Soares-Miranda L, Imamura F, Siscovick D, et al. Physical activity, physical fitness, and leukocyte telomere length. Med Sci Sports Exerc. 2015;47(12):2525–34.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Zhu H, Wang X, Gutin B, et al. Leukocyte telomere length in healthy Caucasian and African-American adolescents: relationships with race, sex, adiposity, adipokines, and physical activity. J Pediatr. 2011;158(2):215–20.

    Article  PubMed  Google Scholar 

  147. Garatachea N, Santos-Lozano A, Sanchis-Gomar F, et al. Elite athletes live longer than the general population: a meta-analysis. Mayo Clin Proc. 2014;89(9):1195–200.

    Article  PubMed  Google Scholar 

  148. Werner C, Furster T, Widmann T, et al. Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall. Circulation. 2009;120(24):2438–47.

    Article  PubMed  Google Scholar 

  149. LaRocca TJ, Seals DR, Pierce GL. Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity. Mech Ageing Dev. 2010;131(2):165–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Denham J, Nelson CP, O’Brien BJ, et al. Longer leukocyte telomeres are associated with ultra-endurance exercise independent of cardiovascular risk factors. PLoS One. 2013;8(7):e69377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Denham J, O’Brien BJ, Prestes PR, et al. Increased expression of telomere-regulating genes in endurance athletes with long leukocyte telomeres. J Appl Physiol (1985). 2015;120(2):148–58.

    Article  Google Scholar 

  152. Mathur S, Ardestani A, Parker B, et al. Telomere length and cardiorespiratory fitness in marathon runners. J Investig Med. 2013;61(3):613–5.

    Article  PubMed  Google Scholar 

  153. Laine MK, Eriksson JG, Kujala UM, et al. Effect of intensive exercise in early adult life on telomere length in later life in men. J Sports Sci Med. 2015;14(2):239–45.

    PubMed  PubMed Central  Google Scholar 

  154. Mason C, Risques RA, Xiao L, et al. Independent and combined effects of dietary weight loss and exercise on leukocyte telomere length in postmenopausal women. Obesity (Silver Spring). 2013;21(12):E549–54.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Krauss J, Farzaneh-Far R, Puterman E, et al. Physical fitness and telomere length in patients with coronary heart disease: findings from the Heart and Soul Study. PLoS One. 2011;6(11):e26983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Osthus IB, Sgura A, Berardinelli F, et al. Telomere length and long-term endurance exercise: does exercise training affect biological age? A pilot study. PLoS One. 2012;7(12):e52769.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Ponsot E, Lexell J, Kadi F. Skeletal muscle telomere length is not impaired in healthy physically active old women and men. Muscle Nerve. 2008;37(4):467–72.

    Article  CAS  PubMed  Google Scholar 

  158. Venturelli M, Morgan GR, Donato AJ, et al. Cellular aging of skeletal muscle: telomeric and free radical evidence that physical inactivity is responsible and not age. Clin Sci (Lond). 2014;127(6):415–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Collins M, Renault V, Grobler LA, et al. Athletes with exercise-associated fatigue have abnormally short muscle DNA telomeres. Med Sci Sports Exerc. 2003;35(9):1524–8.

    Article  CAS  PubMed  Google Scholar 

  160. Rae DE, Vignaud A, Butler-Browne GS, et al. Skeletal muscle telomere length in healthy, experienced, endurance runners. Eur J Appl Physiol. 2010;109(2):323–30.

    Article  PubMed  Google Scholar 

  161. Kadi F, Ponsot E, Piehl-Aulin K, et al. The effects of regular strength training on telomere length in human skeletal muscle. Med Sci Sports Exerc. 2008;40(1):82–7.

    Article  PubMed  Google Scholar 

  162. Ornish D, Lin J, Daubenmier J, et al. Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol. 2008;9(11):1048–57.

    Article  CAS  PubMed  Google Scholar 

  163. Ornish D, Lin J, Chan JM, et al. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol. 2013;14(11):1112–20.

    Article  CAS  PubMed  Google Scholar 

  164. Melk A, Tegtbur U, Hilfiker-Kleiner D, et al. Improvement of biological age by physical activity. Int J Cardiol. 2014;176(3):1187–9.

    Article  PubMed  Google Scholar 

  165. Puterman E, Lin J, Blackburn E, et al. The power of exercise: buffering the effect of chronic stress on telomere length. PLoS One. 2010;5(5):e10837.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Denham J, Marques FZ, Charchar FJ. Leukocyte telomere length variation due to DNA extraction method. BMC Res Notes. 2014;7(1):877.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Aviv A. The epidemiology of human telomeres: faults and promises. J Gerontol A Biol Sci Med Sci. 2008;63(9):979–83.

    Article  PubMed  Google Scholar 

  168. Aviv A, Hunt SC, Lin J, et al. Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucleic Acids Res. 2011;39(20):e134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Martin-Ruiz CM, Baird D, Roger L, et al. Reproducibility of telomere length assessment: an international collaborative study. Int J Epidemiol. 2015;44(5):1673–83.

    Article  PubMed  Google Scholar 

  170. Bouchard C, Daw EW, Rice T, et al. Familial resemblance for VO2max in the sedentary state: the HERITAGE family study. Med Sci Sports Exerc. 1998;30(2):252–8.

    Article  CAS  PubMed  Google Scholar 

  171. Bouchard C, An P, Rice T, et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol (1985). 1999;87(3):1003–8.

    CAS  Google Scholar 

  172. Dyrstad SM, Hansen BH, Holme IM, et al. Comparison of self-reported versus accelerometer-measured physical activity. Med Sci Sports Exerc. 2014;46(1):99–106.

    Article  PubMed  Google Scholar 

  173. Garriguet D, Colley RC. A comparison of self-reported leisure-time physical activity and measured moderate-to-vigorous physical activity in adolescents and adults. Health Rep. 2014;25(7):3–11.

    PubMed  Google Scholar 

  174. Tully MA, Panter J, Ogilvie D. Individual characteristics associated with mismatches between self-reported and accelerometer-measured physical activity. PLoS One. 2014;9(6):e99636.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Ludlow AT, Witkowski S, Marshall MR, et al. Chronic exercise modifies age-related telomere dynamics in a tissue-specific fashion. J Gerontol A Biol Sci Med Sci. 2012;67(9):911–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Werner C, Hanhoun M, Widmann T, et al. Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol. 2008;52(6):470–82.

    Article  CAS  PubMed  Google Scholar 

  177. Wolf SA, Melnik A, Kempermann G. Physical exercise increases adult neurogenesis and telomerase activity, and improves behavioral deficits in a mouse model of schizophrenia. Brain Behav Immun. 2011;25(5):971–80.

    Article  CAS  PubMed  Google Scholar 

  178. Chilton WL, Marques FZ, West J, et al. Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells. PLoS One. 2014;9(4):e92088.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Laye MJ, Solomon TP, Karstoft K, et al. Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event. J Appl Physiol (1985). 2012;112(5):773–81.

    Article  CAS  Google Scholar 

  180. Ludlow AT, Lima LC, Wang J, et al. Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK. J Appl Physiol (1985). 2012;113(11):1737–46.

    Article  CAS  PubMed Central  Google Scholar 

  181. Schuler G, Adams V, Goto Y. Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J. 2013;34(24):1790–9.

    Article  CAS  PubMed  Google Scholar 

  182. Sanz C, Gautier JF, Hanaire H. Physical exercise for the prevention and treatment of type 2 diabetes. Diabetes Metab. 2010;36(5):346–51.

    Article  CAS  PubMed  Google Scholar 

  183. Slentz CA, Houmard JA, Kraus WE. Modest exercise prevents the progressive disease associated with physical inactivity. Exerc Sport Sci Rev. 2007;35(1):18–23.

    Article  PubMed  Google Scholar 

  184. Oeseburg H, de Boer RA, van Gilst WH, et al. Telomere biology in healthy aging and disease. Pflugers Arch. 2010;459(2):259–68.

    Article  CAS  PubMed  Google Scholar 

  185. Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009;3(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  186. Ludlow AT, Spangenburg EE, Chin ER, et al. Telomeres shorten in response to oxidative stress in mouse skeletal muscle fibers. J Gerontol A Biol Sci Med Sci. 2014;69(7):821–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Gleeson M, Bishop NC, Stensel DJ, et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011;11(9):607–15.

    Article  CAS  PubMed  Google Scholar 

  188. Leeuwenburgh C, Heinecke JW. Oxidative stress and antioxidants in exercise. Curr Med Chem. 2001;8(7):829–38.

    Article  CAS  PubMed  Google Scholar 

  189. Shin YA, Lee JH, Song W, et al. Exercise training improves the antioxidant enzyme activity with no changes of telomere length. Mech Ageing Dev. 2008;129(5):254–60.

    Article  CAS  PubMed  Google Scholar 

  190. Dinami R, Ercolani C, Petti E, et al. miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res. 2014;74(15):4145–56.

    Article  CAS  PubMed  Google Scholar 

  191. Luke B, Lingner J. TERRA: telomeric repeat-containing RNA. EMBO J. 2009;28(17):2503–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Benetti R, Gonzalo S, Jaco I, et al. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008;15(9):998.

    Article  CAS  PubMed  Google Scholar 

  193. Yamada Y, Nishida T, Horibe H, et al. Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. Int J Mol Med. 2014;33(5):1355–63.

    CAS  PubMed  Google Scholar 

  194. Ribel-Madsen R, Fraga MF, Jacobsen S, et al. Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes. PLoS One. 2012;7(12):e51302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Denham J, Marques FZ, O’Brien BJ, et al. Exercise: putting action into our epigenome. Sports Med. 2014;44(2):189–209.

    Article  PubMed  Google Scholar 

  196. Voisin S, Eynon N, Yan X, et al. Exercise training and DNA methylation in humans. Acta Physiol (Oxf). 2015;213(1):39–59.

    Article  CAS  PubMed  Google Scholar 

  197. McGee SL, Hargreaves M. Histone modifications and exercise adaptations. J Appl Physiol (1985). 2011;110(1):258–63.

    Article  CAS  Google Scholar 

  198. Denham J, O’Brien BJ, Marques FZ, et al. Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise. J Appl Physiol (1985). 2015;118(4):475–88.

    Article  CAS  Google Scholar 

  199. Guilleret I, Benhattar J. Unusual distribution of DNA methylation within the hTERT CpG island in tissues and cell lines. Biochem Biophys Res Commun. 2004;325(3):1037–43.

    Article  CAS  PubMed  Google Scholar 

  200. Zhu J, Zhao Y, Wang S. Chromatin and epigenetic regulation of the telomerase reverse transcriptase gene. Protein Cell. 2010;1(1):22–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Renaud S, Loukinov D, Bosman FT, et al. CTCF binds the proximal exonic region of hTERT and inhibits its transcription. Nucleic Acids Res. 2005;33(21):6850–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Liu L, Saldanha SN, Pate MS, et al. Epigenetic regulation of human telomerase reverse transcriptase promoter activity during cellular differentiation. Genes Chromosomes Cancer. 2004;41(1):26–37.

    Article  CAS  PubMed  Google Scholar 

  203. Benetti R, Gonzalo S, Jaco I, et al. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008;15(3):268–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Borghini A, Giardini G, Tonacci A, et al. Chronic and acute effects of endurance training on telomere length. Mutagenesis. 2015;30(5):711–6.

    Article  CAS  PubMed  Google Scholar 

  205. Loprinzi PD, Loenneke JP, Blackburn EH. Movement-based behaviors and leukocyte telomere length among US adults. Med Sci Sports Exerc. 2015;47(11):2347–52.

    Article  CAS  PubMed  Google Scholar 

  206. Weischer M, Bojesen SE, Nordestgaard BG. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4576 general population individuals with repeat measurements 10 years apart. PLoS Genet. 2014;10(3):e1004191.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Yang JH, Han H, Jang SY, et al. A comparison of the Ghent and revised Ghent nosologies for the diagnosis of Marfan syndrome in an adult Korean population. Am J Med Genet A. 2012;158A(5):989–95.

    Article  PubMed  Google Scholar 

  208. Kingma EM, de Jonge P, van der Harst P, et al. The association between intelligence and telomere length: a longitudinal population based study. PLoS One. 2012;7(11):e49356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Mirabello L, Huang WY, Wong JY, et al. The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer. Aging Cell. 2009;8(4):405–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Woo J, Tang N, Leung J. No association between physical activity and telomere length in an elderly Chinese population 65 years and older. Arch Intern Med. 2008;168(19):2163–4.

    Article  PubMed  Google Scholar 

  211. Loprinzi PD. Cardiorespiratory capacity and leukocyte telomere length among adults in the United States. Am J Epidemiol. 2015;182(3):198–201.

    Article  PubMed  Google Scholar 

  212. Maynard S, Keijzers G, Hansen AM, et al. Associations of subjective vitality with DNA damage, cardiovascular risk factors and physical performance. Acta Physiol (Oxf). 2015;213(1):156–70.

    Article  CAS  PubMed  Google Scholar 

  213. Simpson RJ, Cosgrove C, Chee MM, et al. Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans. Exerc Immunol Rev. 2010;16:40–55.

    PubMed  Google Scholar 

  214. Bruunsgaard H, Jensen MS, Schjerling P, et al. Exercise induces recruitment of lymphocytes with an activated phenotype and short telomeres in young and elderly humans. Life Sci. 1999;65(24):2623–33.

    Article  CAS  PubMed  Google Scholar 

  215. Hovatta I, de Mello VD, Kananen L, et al. Leukocyte telomere length in the Finnish Diabetes Prevention Study. PLoS One. 2012;7(4):e34948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Botha M, Grace L, Bugarith K, et al. The impact of voluntary exercise on relative telomere length in a rat model of developmental stress. BMC Res Notes. 2012;5:697.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to express their gratitude to the Federation University Australia “Self-sustaining Regions Research and Innovation Initiative”, an Australian Government Collaborative Research Network (CRN).

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  1. School of Science and Technology, University of New England, Armidale, NSW, Australia

    Joshua Denham

  2. Faculty of Health, Federation University Australia, University Drive, Mt Helen, VIC, Australia

    Brendan J. O’Brien

  3. Faculty of Science and Technology, Federation University Australia, University Drive, Mt Helen, VIC, Australia

    Fadi J. Charchar

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Correspondence to Joshua Denham.

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Joshua Denham is supported by an Australian Post-graduate Award scholarship. Fadi Charchar is supported by the Lew Carty Charitable fund and National Health and Medical Research Council. No other sources of funding were used to assist in the preparation of this article.

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Joshua Denham, Brendan O’Brien and Fadi Charchar declare that they have no conflicts of interest relevant to the content of this review.

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Denham, J., O’Brien, B.J. & Charchar, F.J. Telomere Length Maintenance and Cardio-Metabolic Disease Prevention Through Exercise Training. Sports Med 46, 1213–1237 (2016). https://doi.org/10.1007/s40279-016-0482-4

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