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Telomere, aging and age-related diseases

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Abstract

Aging is an inevitable biological process that affects most living organisms. The process of aging is regulated at the level of the organism, as well as at the level of tissues and cells. Despite the enormous consequences associated with the aging process, relatively little systematic effort has been expended on the scientific understanding of this important life process. Many theories have been proposed to explain the aging process, the centerpiece of which is molecular damage. Located at the ends of eukaryotic chromosomes and synthesized by telomerase, telomeres maintain the stabilization of chromosomes. Thus, the loss of telomeres may lead to DNA damage. The relationship between cellular senescence and telomere shortening is well established. Furthermore, telomere attrition occurs with age, and is proposed to be a fundamental factor in the aging process. Here, we review the contemporary literatures to explore the current views on the correlation of telomere loss and telomerase action with aging and age-related diseases.

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References

  1. Reaper PM, di Fagagna FD, Jackson SP (2004) Activation of the DNA damage response by telomere attrition—a passage to cellular senescence. Cell Cycle 3:543–546

    Article  PubMed  CAS  Google Scholar 

  2. Shammas MA (2011) Telomeres, lifestyle, cancer, and aging. Current Opinion Clin Nutr Metab Care 14:28–34

    Article  CAS  Google Scholar 

  3. Takubo K, Aida J, Izumiyama-Shimomura N, Ishikawa N, Sawabe M, Kurabayashi R, Shiraishi H et al (2010) Changes of telomere length with aging. Geriatr Gerontol Int 10:S197–S206

    Article  PubMed  Google Scholar 

  4. Aubert G, Lansdorp PM (2008) Telomeres and aging. Physiol Rev 88:557–579

    Article  PubMed  CAS  Google Scholar 

  5. Wong LSM, van der Harst P, de Boer RA, Huzen J, van Gilst WH, van Veldhuisen DJ (2010) Aging, telomeres and heart failure. Heart Fail Rev 15:479–486

    Article  PubMed  CAS  Google Scholar 

  6. Huzen J, de Boer RA, van Veldhuisen DJ, van Gilst WH, van der Harst P (2010) The emerging role of telomere biology in cardiovascular disease. Frontiers Biosci Landmark 15:35–45

    Article  Google Scholar 

  7. Oeseburg H, de Boer RA, van Gilst WH, van der Harst P (2010) Telomere biology in healthy aging and disease. Pflugers Arch 459:259–268

    Article  PubMed  CAS  Google Scholar 

  8. Lin KW, Yan J (2005) The telomere length dynamic and methods of its assessment. J Cell Mol Med 9:977–989

    Article  PubMed  CAS  Google Scholar 

  9. Zakian VA (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141–172

    Article  PubMed  CAS  Google Scholar 

  10. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Mammalian telomeres end in a large duplex loop. Cell 97:503–514

    Article  PubMed  CAS  Google Scholar 

  11. Stewart JA, Chaiken MF, Wang F, Price CM (2012) Maintaining the end: roles of telomere proteins in end-protection, telomere replication and length regulation. Mutat Res 730:12–19

    Article  PubMed  CAS  Google Scholar 

  12. Broccoli D, Smogorzewska A, Chong L, de Lange T (1997) Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet 17:231–235

    Article  PubMed  CAS  Google Scholar 

  13. Kim SH, Kaminker P, Campisi J (1999) TIN2, a new regulator of telomere length in human cells. Nat Genet 23:405–412

    Article  PubMed  CAS  Google Scholar 

  14. McKerlie MA, Lin S, Zhu XD (2012) ATM regulates proteasome-dependent subnuclear localization of TRF1, which is important for telomere maintenance. Nucleic Acids Res 40:3975–3989

    Article  PubMed  CAS  Google Scholar 

  15. Mason M, Schuller A, Skordalakes E (2011) Telomerase structure function. Curr Opin Struct Biol 21:92–100

    Article  PubMed  CAS  Google Scholar 

  16. Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31:9–18

    Article  PubMed  CAS  Google Scholar 

  17. Landberg G, Nielsen NH, Nilsson P, Emdin SO, Cajander J, Roos G (1997) Telomerase activity is associated with cell cycle deregulation in human breast cancer. Cancer Res 57:549–554

    PubMed  CAS  Google Scholar 

  18. Halvorsen TL, Leibowitz G, Levine F (1999) Telomerase activity is sufficient to allow transformed cells to escape from crisis. Mol Cell Biol 19:1864–1870

    PubMed  CAS  Google Scholar 

  19. Shay JW, Wright WE (2005) Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26:867–874

    Article  PubMed  CAS  Google Scholar 

  20. Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, Mak J et al (2000) Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science 288:665–669

    Article  PubMed  CAS  Google Scholar 

  21. Lansdorp PM (2000) Repair of telomeric DNA prior to replicative senescence. Mech Ageing Dev 118:23–34

    Article  PubMed  CAS  Google Scholar 

  22. Martinez P, Blasco MA (2011) Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 11:161–176

    Article  PubMed  CAS  Google Scholar 

  23. Diaz VA, Mainous AG 3rd, Everett CJ, Schoepf UJ, Codd V, Samani NJ (2010) Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium. Am J Cardiol 106:659–663

    Article  PubMed  CAS  Google Scholar 

  24. Cassidy A, De Vivo I, Liu Y, Han J, Prescott J, Hunter DJ, Rimm EB (2010) Associations between diet, lifestyle factors, and telomere length in women. Am J Clin Nutr 91:1273–1280

    Article  PubMed  CAS  Google Scholar 

  25. Ornish D, Lin J, Daubenmier J, Weidner G, Epel E, Kemp C, Magbanua MJ et al (2008) Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol 9:1048–1057

    Article  PubMed  CAS  Google Scholar 

  26. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW et al (1992) Telomere Length Predicts Replicative Capacity of Human Fibroblasts. Proc Natl Acad Sci USA 89:10114–10118

    Article  PubMed  CAS  Google Scholar 

  27. Greenberg RA (2005) Telomeres, crisis and cancer. Curr Mol Med 5:213–218

    Article  PubMed  CAS  Google Scholar 

  28. di Fagagna FD, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, von Zglinicki T, Saretzki G et al (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426:194–198

    Article  Google Scholar 

  29. Karlseder J, Broccoli D, Dai YM, Hardy S, de Lange T (1999) p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283:1321–1325

    Article  PubMed  CAS  Google Scholar 

  30. Wright WE, Brasiskyte D, Piatyszek MA, Shay JW (1996) Experimental elongation of telomeres extends the lifespan of immortal x normal cell hybrids. EMBO J 15:1734–1741

    PubMed  CAS  Google Scholar 

  31. Allsopp RC, Harley CB (1995) Evidence for a critical telomere length in senescent human fibroblasts. Exp Cell Res 219:130–136

    Article  PubMed  CAS  Google Scholar 

  32. Huang XQ, Wang J, Liu JP, Feng H, Liu WB, Yan Q, Liu Y et al (2005) hTERT extends proliferative lifespan and prevents oxidative stress-induced apoptosis in human lens epithelial cells. Invest Ophthalmol Vis Sci 46:2503–2513

    Article  PubMed  Google Scholar 

  33. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352

    Article  PubMed  CAS  Google Scholar 

  34. Wieser M, Stadler G, Jennings P, Streubel B, Pfaller W, Ambros P, Riedl C et al (2008) hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics. Am J Physiol Renal Physiol 295:F1365–F1375

    Article  PubMed  CAS  Google Scholar 

  35. Njajou OT, Hsueh WC, Blackburn EH, Newman AB, Wu SH, Li RL, Simonsick EM et al (2009) Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J Gerontol Ser A Biol Sci Med Sci 64:860–864

    Article  Google Scholar 

  36. Hunt SC, Chen W, Gardner JP, Kimura M, Srinivasan SR, Eckfeldt JH, Berenson GS et al (2008) Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study. Aging Cell 7:451–458

    Article  PubMed  CAS  Google Scholar 

  37. Ren F, Li CY, Xi HJ, Wen YF, Huang KQ (2009) Estimation of human age according to telomere shortening in peripheral blood leukocytes of Tibetan. Am J Forensic Med Pathol 30:252–255

    Article  PubMed  CAS  Google Scholar 

  38. Vaziri H, Schachter F, Uchida I, Wei L, Zhu XM, Effros R, Cohen D et al (1993) Loss of telomeric DNA during aging of normal and trisomy-21 human-lymphocytes. Am J Hum Genet 52:661–667

    PubMed  CAS  Google Scholar 

  39. Andrews NP, Fujii H, Goronzy JJ, Weyand CM (2010) Telomeres and immunological diseases of aging. Gerontology 56:390–403

    Article  PubMed  CAS  Google Scholar 

  40. von Zglinicki T, Martin-Ruiz CM (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5:197–203

    Article  Google Scholar 

  41. Harley CB (2005) Telomerase therapeutics for degenerative diseases. Curr Mol Med 5:205–211

    Article  PubMed  CAS  Google Scholar 

  42. Asselbergs FW, van der Harst P, Jessurun GAJ, Tio RA, van Gilst WH (2005) Clinical impact of vasomotor function assessment and the role of ACE-inhibitors and statins. Vascul Pharmacol 42:125–140

    Article  PubMed  CAS  Google Scholar 

  43. Mainous AG, Diaz VA (2010) Telomere length as a risk marker for cardiovascular disease: the next big thing? Expert Rev Mol Diagn 10:969–971

    Article  PubMed  CAS  Google Scholar 

  44. De Meyer T, Rietzschel ER, De Buyzere ML, Van Criekinge W, Bekaert S (2011) Telomere length and cardiovascular aging: the means to the ends? Ageing Res Rev 10:297–303

    Article  PubMed  Google Scholar 

  45. Chang E, Harley CB (1995) Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci USA 92:11190–11194

    Article  PubMed  CAS  Google Scholar 

  46. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I (2002) Endothelial cell senescence in human atherosclerosis—role of telomere in endothelial dysfunction. Circulation 105:1541–1544

    Article  PubMed  CAS  Google Scholar 

  47. Fenton M, Barker S, Kurz DJ, Erusalimsky JD (2001) Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries. Arterioscler Thromb Vasc Biol 21:220–226

    Article  PubMed  CAS  Google Scholar 

  48. Yang ZW, Huang X, Jiang H, Zhang YR, Liu HX, Qin C, Eisner GM et al (2009) Short telomeres and prognosis of hypertension in a chinese population. Hypertension 53:639–695

    Article  PubMed  CAS  Google Scholar 

  49. Imanishi T, Moriwaki C, Hano T, Nishio I (2005) Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 23:1831–1837

    Article  PubMed  CAS  Google Scholar 

  50. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, Nadal-Ginard B et al (2003) Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. EMBO J 22:131–139

    Article  PubMed  CAS  Google Scholar 

  51. Wong LSM, de Boer RA, Samani NJ, van Veldhuisen DJ, Harst PD (2008) Telomere biology in heart failure. Eur J Heart Fail 10:1049–1056

    Article  PubMed  CAS  Google Scholar 

  52. van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, van Gilst WH et al (2007) Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol 49:1459–1464

    Article  PubMed  Google Scholar 

  53. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A et al (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA 100:10440–10445

    Article  PubMed  CAS  Google Scholar 

  54. Oh H, Wang SC, Prahash A, Sano M, Moravec CS, Taffett GE, Michael LH et al (2003) Telomere attrition and Chk2 activation in human heart failure. Proc Natl Acad Sci USA 100:5378–5383

    Article  PubMed  CAS  Google Scholar 

  55. Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F et al (2003) Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 93:604–613

    Article  PubMed  CAS  Google Scholar 

  56. Zee RYL, Castonguay AJ, Barton NS, Germer S, Martin M (2010) Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study. Transl Res 155:166–169

    Article  PubMed  CAS  Google Scholar 

  57. Salpea KD, Talmud PJ, Cooper JA, Maubaret CG, Stephens JW, Abelak K, Humphries SE (2010) Association of telomere length with type 2 diabetes, oxidative stress and UCP2 gene variation. Atherosclerosis 209:42–50

    Article  PubMed  CAS  Google Scholar 

  58. Fyhrquist F, Tiitu A, Saijonmaa O, Forsblom C, Groop PH (2010) Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes. J Intern Med 267:278–286

    Article  PubMed  CAS  Google Scholar 

  59. Astrup AS, Tarnow L, Jorsal A, Lajer M, Nzietchueng R, Benetos A, Rossing P et al (2010) Telomere length predicts all-cause mortality in patients with type 1 diabetes. Diabetologia 53:45–48

    Article  PubMed  CAS  Google Scholar 

  60. Kuhlow D, Florian S, von Figura G, Weimer S, Schulz N, Petzke KJ, Zarse K et al (2010) Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging (US) 2:650–658

    CAS  Google Scholar 

  61. Adaikalakoteswari A, Balasubramanyam M, Ravikumar R, Deepa R, Mohan V (2007) Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy. Atherosclerosis 195:83–89

    Article  PubMed  CAS  Google Scholar 

  62. Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A, Kimura M et al (2006) Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 5:325–330

    Article  PubMed  CAS  Google Scholar 

  63. Hahn WC (2003) Role of telomeres and telomerase in the pathogenesis of human cancer. J Clin Oncol 21:2034–2043

    Article  PubMed  CAS  Google Scholar 

  64. Chung HK, Cheong C, Song J, Lee HW (2005) Extratelomeric functions of telomerase. Curr Mol Med 5:233–241

    Article  PubMed  CAS  Google Scholar 

  65. Wu XF, Amos CI, Zhu Y, Zhao H, Grossman BH, Shay JW, Luo S et al (2003) Telomere dysfunction: a potential cancer predisposition factor. J Natl Cancer Inst 95:1211–1218

    Article  PubMed  CAS  Google Scholar 

  66. Mu YC, Zhang Q, Mei LH, Liu XS, Yang WL, Yu JR (2011) Telomere shortening occurs early during gastrocarcinogenesis. Med Oncol. doi:10.1007/s12032-011-9866-3

  67. Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL et al (1999) Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5:1164–1170

    Article  PubMed  CAS  Google Scholar 

  68. Guittat L, Alberti P, Mergny JL, Riou JF, Teulade-Fichou MP, Mailliet P (2001) Telomerase inhibitors: possible consequences in cancer therapy. M S-Med Sci 17:1076–1081

    Google Scholar 

  69. Perry PJ, Arnold JRP, Jenkins TC (2001) Telomerase inhibitors for the treatment of cancer: the current perspective. Expert Opin Investig Drugs 10:2141–2156

    Article  PubMed  CAS  Google Scholar 

  70. Hashizume R, Gupta N (2010) Telomerase inhibitors for the treatment of brain tumors and the potential of intranasal delivery. Curr Opin Mol Ther 12:168–175

    PubMed  CAS  Google Scholar 

  71. Agrawal A, Dang S, Gabrani R (2012) Recent patents on anti-telomerase cancer therapy. Recent Pat Anticancer Drug Discov 7:102–117

    Article  PubMed  CAS  Google Scholar 

  72. Malavolta M, Mocchegiani E, Bertoni-Freddari C (2004) New trends in biomedical aging research. Gerontology 50:420–424

    Article  PubMed  Google Scholar 

  73. Goronzy JJ, Fujii H, Weyand CM (2006) Telomeres, immune aging and autoimmunity. Exp Gerontol 41:246–251

    Article  PubMed  CAS  Google Scholar 

  74. Effros RB (2003) Genetic alterations in the ageing immune system: impact on infection and cancer. Mech Ageing Dev 124:71–77

    Article  PubMed  CAS  Google Scholar 

  75. Georgin-Lavialle S, Aouba A, Mouthon L, Londono-Vallejo JA, Lepelletier Y, Gabet AS, Hermine O (2010) The telomere/telomerase system in autoimmune and systemic immune-mediated diseases. Autoimmun Rev 9:646–651

    Article  PubMed  CAS  Google Scholar 

  76. Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A (2004) Is immunosenescence infectious? Trends Immunol 25:406–410

    Article  PubMed  CAS  Google Scholar 

  77. Akbar AN, Beverley PCL, Salmon M (2004) Opinion: will telomere erosion lead to a loss of T-cell memory? Nat Rev Immunol 4:737–743

    Article  PubMed  CAS  Google Scholar 

  78. Effros RB, Boucher N, Porter V, Zhu XM, Spaulding C, Walford RL, Kronenberg M et al (1994) Decline in Cd28(+) T-cells in centenarians and in long-term t-cell cultures—a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol 29:601–609

    Article  PubMed  CAS  Google Scholar 

  79. Weng NP, Levine BL, June CH, Hodes RJ (1996) Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med 183:2471–2479

    Article  PubMed  CAS  Google Scholar 

  80. Spaulding C, Guo W, Effros RB (1999) Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Exp Gerontol 34:633–644

    Article  PubMed  CAS  Google Scholar 

  81. Weng NP (2001) Interplay between telomere length and telomerase in human leukocyte differentiation and aging. J Leukoc Biol 70:861–867

    PubMed  CAS  Google Scholar 

  82. Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395

    Article  PubMed  CAS  Google Scholar 

  83. Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555

    Article  PubMed  CAS  Google Scholar 

  84. Mason PJ, Wilson DB, Bessler M (2005) Dyskeratosis congenita—a disease of dysfunctional telomere maintenance. Curr Mol Med 5:159–170

    Article  PubMed  CAS  Google Scholar 

  85. Walne AJ, Marrone A, Dokal I (2005) Dyskeratosis congenita: a disorder of defective telomere maintenance? Int J Hematol 82:184–189

    Article  PubMed  CAS  Google Scholar 

  86. Bessler M, Wilson DB, Mason PJ (2004) Dyskeratosis congenita and telomerase. Curr Opin Pediatr 16:23–28

    Article  PubMed  Google Scholar 

  87. Mather KA, Jorm AF, Parslow RA, Christensen H (2011) Is telomere length a biomarker of aging? A review. J Gerontol Ser A Biol Sci Med Sci 66:202–213

    Article  Google Scholar 

  88. Cong YS, Shay JW (2008) Actions of human telomerase beyond telomeres. Cell Res 18:725–732

    Article  PubMed  CAS  Google Scholar 

  89. Egan CA, Savre-Train I, Shay JW, Wilson SE, Bourne WM (1998) Analysis of telomere lengths in human corneal endothelial cells from donors of different ages. Invest Ophthalmol Vis Sci 39:648–653

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural and Science Foundation of China (30830062, 30971529, 30840047).

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Authors and Affiliations

  1. Institute of Anthropology, Liaoning Medical University, No.40, Section 3, Songpo Road, Jinzhou, Liaoning, 121001, People’s Republic of China

    Huanjiu Xi, Fu Ren & Hailong Zhang

  2. Department of Physiology, School of Basic Medical Sciences, Wuhan University, Hubei, 430071, People’s Republic of China

    Changyong Li

  3. Department of Anatomy, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Luping Zhang

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  1. Huanjiu Xi
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Correspondence to Huanjiu Xi.

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Xi, H., Li, C., Ren, F. et al. Telomere, aging and age-related diseases. Aging Clin Exp Res 25, 139–146 (2013). https://doi.org/10.1007/s40520-013-0021-1

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