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
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
Shammas MA (2011) Telomeres, lifestyle, cancer, and aging. Current Opinion Clin Nutr Metab Care 14:28–34
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
Aubert G, Lansdorp PM (2008) Telomeres and aging. Physiol Rev 88:557–579
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
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
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
Lin KW, Yan J (2005) The telomere length dynamic and methods of its assessment. J Cell Mol Med 9:977–989
Zakian VA (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141–172
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
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
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
Kim SH, Kaminker P, Campisi J (1999) TIN2, a new regulator of telomere length in human cells. Nat Genet 23:405–412
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
Mason M, Schuller A, Skordalakes E (2011) Telomerase structure function. Curr Opin Struct Biol 21:92–100
Artandi SE, DePinho RA (2010) Telomeres and telomerase in cancer. Carcinogenesis 31:9–18
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
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
Shay JW, Wright WE (2005) Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26:867–874
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
Lansdorp PM (2000) Repair of telomeric DNA prior to replicative senescence. Mech Ageing Dev 118:23–34
Martinez P, Blasco MA (2011) Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 11:161–176
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
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
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
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
Greenberg RA (2005) Telomeres, crisis and cancer. Curr Mol Med 5:213–218
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
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
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
Allsopp RC, Harley CB (1995) Evidence for a critical telomere length in senescent human fibroblasts. Exp Cell Res 219:130–136
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
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
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
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
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
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
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
Andrews NP, Fujii H, Goronzy JJ, Weyand CM (2010) Telomeres and immunological diseases of aging. Gerontology 56:390–403
von Zglinicki T, Martin-Ruiz CM (2005) Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med 5:197–203
Harley CB (2005) Telomerase therapeutics for degenerative diseases. Curr Mol Med 5:205–211
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
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
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
Chang E, Harley CB (1995) Telomere length and replicative aging in human vascular tissues. Proc Natl Acad Sci USA 92:11190–11194
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Hahn WC (2003) Role of telomeres and telomerase in the pathogenesis of human cancer. J Clin Oncol 21:2034–2043
Chung HK, Cheong C, Song J, Lee HW (2005) Extratelomeric functions of telomerase. Curr Mol Med 5:233–241
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
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
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
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
Perry PJ, Arnold JRP, Jenkins TC (2001) Telomerase inhibitors for the treatment of cancer: the current perspective. Expert Opin Investig Drugs 10:2141–2156
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
Agrawal A, Dang S, Gabrani R (2012) Recent patents on anti-telomerase cancer therapy. Recent Pat Anticancer Drug Discov 7:102–117
Malavolta M, Mocchegiani E, Bertoni-Freddari C (2004) New trends in biomedical aging research. Gerontology 50:420–424
Goronzy JJ, Fujii H, Weyand CM (2006) Telomeres, immune aging and autoimmunity. Exp Gerontol 41:246–251
Effros RB (2003) Genetic alterations in the ageing immune system: impact on infection and cancer. Mech Ageing Dev 124:71–77
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
Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A (2004) Is immunosenescence infectious? Trends Immunol 25:406–410
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
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
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
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
Weng NP (2001) Interplay between telomere length and telomerase in human leukocyte differentiation and aging. J Leukoc Biol 70:861–867
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
Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402:551–555
Mason PJ, Wilson DB, Bessler M (2005) Dyskeratosis congenita—a disease of dysfunctional telomere maintenance. Curr Mol Med 5:159–170
Walne AJ, Marrone A, Dokal I (2005) Dyskeratosis congenita: a disorder of defective telomere maintenance? Int J Hematol 82:184–189
Bessler M, Wilson DB, Mason PJ (2004) Dyskeratosis congenita and telomerase. Curr Opin Pediatr 16:23–28
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
Cong YS, Shay JW (2008) Actions of human telomerase beyond telomeres. Cell Res 18:725–732
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
Acknowledgments
This work was supported by grants from the National Natural and Science Foundation of China (30830062, 30971529, 30840047).
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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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DOI: https://doi.org/10.1007/s40520-013-0021-1