Abstract
Telomeres are distinctive structures, composed of a repetitive DNA sequence and associated proteins, that cap the ends of linear chromosomes. Telomeres are essential for maintaining the integrity and stability of eukaryotic genomes. In addition, under some circumstances, telomeres can influence cellular gene expression. In mammals, the length, structure, and function of telomeres have been proposed to contribute to cellular and organismal phenotypes associated with cancer and aging. Here, we discuss what is known about the basis for the links between telomeres, aging and cancer, and some of the known and proposed consequences of telomere dysfunction and maintenance for mammalian cells and organisms.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Allsopp RC, Chang E, Kashefi-Aazam M, Rogaev EI, Piatyszek MA, Shay JW, Harley CB . 1995 Exp. Cell Res. 220: 194–200
Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA . 2000 Nature 406: 641–645
Bailey S, Meyne J, Chen DJ, Kurimasa A, Li GC, Lehnert BE, Goodwin EH . 1999 Proc. Natl. Acad. Sci. USA 96: 14899–14904
Bailey SM, Cornforth MN, Kurimasa A, Chen DJ, Goodwin EH . 2001 Science 293: 2462–2465
Baumann P, Cech T . 2001 Science 292: 1171–1175
Blackburn EH . 2000 Nature 408: 53–56
Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW . 1997 Cell 91: 25–34
Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE . 1998 Science 279: 349–352
Broccoli D, Smogorzewska A, Chong L, de Lange T . 1997 Nat. Genet. 17: 231–235
Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel R . 1997 Nature Med. 3: 1271–1274
Buchkovich KJ, Greider CW . 1996 Mol. Cell. Biol. 7: 1443–1454
Cahill DP, Kinzler KW, Vogelstein B, Lengauer C . 1999 Trends Cell Biol. 9: M57–M60
Campisi J, Dimri GP, Hara E . 1996 Handbook of the Biology of Aging E Schneider, J Rowe (eds) Academic Press: New York pp 121–149
Campisi J . 1999 The Molecular Basis of Cell Cycle and Growth Control Stein G, Baserga R, Giordano A, Denhardt D (eds) Wiley-Liss Press: New York pp 348–373
Campisi J . 2000 In Vivo 14: 183–188
Campisi J . 2001 Exp. Gerontol. 36: 607–618
Cha RS, Thilly WG, Zarbl H . 1994 Proc. Natl. Acad. Sci. USA 91: 3749–3753
Chang E, Harley CB . 1995 Proc. Natl. Acad. Sci. USA 92: 11190–11194
Chen Q, Bartholomew JC, Campisi J, Acosta M, Reagen JD, Ames B . 1998 Biochem. J. 332: 43–50
Chi NW, Lodish HF . 2000 J. Biol. Chem. 275: 38437–38444
Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA . 1999 Cell 97: 527–538
Chiu CP, Harley CB . 1997 Proc. Soc. Exp. Biol. Med. 214: 99–106
Chong L, van Steensel B, Broccoli D, Erdjument-Briomage H, Hanish J, Tempst P, de Lange T . 1995 Science 270: 1663–1667
Coviello-McLaughlin GM, Prowse KR . 1997 Nucl. Acids Res. 25: 3051–3058
d'Adda di Fagagna F, Hande MP, Tong WM, Lansdorp PM, Wang ZQ, Jackson SP . 1999 Nat. Genet. 23: 76–80
D'Amours D, Desnoyers S, D'Silva I, Poirier GG . 1999 Biochem. J. 342: 249–268
Deng G, Lu Y, Zlotnikov G, Thor AD, Smith HS . 1996 Science 274: 2057–2059
DePinho R . 2000 Nature 408: 248–254
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith OM, Peacocke M, Campisi J . 1995 Proc. Natl. Acad. Sci. USA 92: 9363–9367
Dollé ME, Giese H, Hopkins CL, Martus HJ, Hausdorff JM, Vijg J . 1997 Nat. Genet. 17: 431–434
Dollé ME, Snyder WK, Gossen JA, Lohman PH, Vijg J . 2000 Proc. Natl. Acad. Sci. USA 97: 8403–8408
Dubrana K, Perrod S, Gasser SM . 2001 Curr. Opin. Cell Biol. 13: 281–289
Dunham MA, Neumann AA, Fasching CL, Reddel RR . 2000 Nat. Genet. 26: 447–450
Effros RB . 1998 Am. J. Hum. Genet. 62: 1003–1007
Funk WD, Wang CK, Shelton DN, Harley CB, Pagon GD, Hoeffler WK . 2000 Exp. Cell Res. 258: 270–278
Gasser SM . 2000 Science 288: 1377–1379
Gonzalez-Suarez E, Samper E, Flores JM, Blasco MA . 2000 Nat. Genet. 26: 114–117
Gonzalez-Suarez E, Samper E, Flores JM, Blasco MA . 2001 EMBO J. 20: 2619–2630
Gray JW, Collins C . 2000 Carcinog. 21: 443–452
Greenberg RA, Chin L, Femino A, Lee KH, Gottlieb GJ, Singer RH, Greider CW, DePinho RA . 1999 Cell 97: 515–525
Greider CW . 1996 Annu. Rev. Biochem. 65: 337–365
Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T . 1999 Cell 97: 503–514
Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen R, Knoll JHM, Meyerson M, Weinberg RA . 1999a Nature Med. 5: 1164–1170
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA . 1999b Nature 400: 464–468
Harlebachor C, Boukamp P . 1996 Proc. Natl. Acad. Sci. USA 93: 6476–6481
Hemann MT, Greider CW . 2000 Nucl. Acid Res. 28: 4474–4478
Herrera E. Samper E, Martin-Caballero J, Flores JM, Lee HW, Blasco MA . 1999 EMBO J. 18: 2950–2960
Herrera E, Martinez AC, Blasco MA . 2000 EMBO J. 19: 472–481
Holt SE, Wright WE, Shay JW . 1997 Eur. J. Canc. 33: 761–766
Hsu HL, Gilley D, Blackburn EH, Chen DJ . 1999 Proc. Natl. Acad. Sci. USA 96: 12454–12458
Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ . 2000 Genes Dev. 14: 2807–2812
Jiang XR, Jimenez G, Chang E, Frolkis M, Jusler B, Sage M, Beeche M, Bodnar AG, Wahl GM, Tlsty TD, Chiu CP . 1999 Nat. Genet. 21: 111–114
Jonason AS, Kunala S, Price GT, Restifo RJ, Spinelli HM, Persing JA, Leffell DJ, Tarone RE, Brash DE . 1996 Proc. Natl. Acad. Sci. USA 93: 14025–14029
Kakuo S, Asaoka K, Ide T . 1999 Biochem. Biophys. Res. Comm. 263: 308–314
Kaminker P, Kim SH, Taylor RD, Zebarjadian Y, Funk WD, Morin GB, Yaswen P, Campisi J . 2001 J. Biol. Chem. 276: 35891–35899
Karlseder J, Broccoli D, Dai Y, Hardy S, de Lange T . 1999 Science 283: 1321–1325
Kim NW, Platyszek M, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW . 1994 Science 266: 2011–2015
Kim SH, Kaminker P, Campisi J . 1999 Nat. Genet. 23: 405–412
Kirkwood TB, Austad SN . 2000 Nature 408: 233–238
Klapper W, Parwaresch R, Krupp G . 2001 Mech. Ageing Dev. 122: 695–712
Kohn KW . 1999 Mol. Biol. Cell 10: 2703–2734
Krtolica A, Parrinello S, Lockette S, Desprez P, Campisi J . 2001 Proc. Natl. Acad. Sci. USA 98: 12071–12077
Lee HW, Blasco MA, Gottlieb GJ, Horner JW, Greider CW, DePinho RA . 1998 Nature 392: 569–574
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB . 1992 J. Mol. Biol. 225: 951–960
Li B, Oestreich S, de Lange T . 2000 Cell 101: 471–483
Lingner J, Cech TR . 1998 Curr. Opin. Genet. Dev. 8: 226–232
Lundberg AS, Hahn WC, Gupta P, Weinberg RA . 2000 Curr. Opin. Cell Biol. 12: 705–709
Makarov VL, Hirose Y, Langmore JP . 1997 Cell 88: 657–666
McEachern MJ, Krauskopf A, Blackburn EH . 2000 Annu. Rev. Genet. 34: 331–358
Miller RA . 1991 Cancer 68: 2496–2501
Mishima K, Handa JT, Aotaki-Keen A, Lutty GA, Morse LS, Hjelmeland LM . 1999 Invest. Ophthalmol. Vis. Sci. 40: 1590–1593
Mitchell JR, Wood E, Collins K . 1999 Nature 402: 551–555
Morales CP, Holt SE, Ouellette M, Kaur KJ, Yan Y, Wilson KS, White MA, Wright WE, Shay JW . 1999 Nat. Genet. 21: 115–118
Munoz-Jordan JL, Cross GA, de Lange T, Griffith JD . 2001 EMBO J. 20: 579–588
Ouellette MM, Liao M, Herbert BS, Johnson M, Holt SE, Liss HS, Shay JW, Wright WE . 2000 J. Biol. Chem. 275: 10072–10076
Paradis V, Youssef N, Dargere D, Ba N, Bonvoust F, Bedossa P . 2001 Hum. Pathol. 32: 327–332
Park CC, Bissell MJ, Barcellos-Hoff MH . 2000 Molec. Med. Today 6: 324–329
Pendergrass WR, Lane MA, Bodkin NL, Hansen BC, Ingram DK, Roth GS, Yi L, Bin H, Wolf NS . 1999 J. Cell. Physiol. 180: 123–130
Prowse KR, Greider CW . 1995 Proc. Natl. Acad. Sci. USA 92: 4818–4822
Rinehart CA, Torti VR . 1997 Molec. Carcinog. 18: 187–192
Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA . 1999 Cell 96: 701–712
Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA . 2000 EMBO Rep. 1: 244–252
Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW . 1997 Cell 88: 593–602
Shay JW, Pereira-Smith OM, Wright WE . 1991 Exp. Cell Res. 196: 33–39
Shay JW, Wright WE . 2001 Novartis Found. Symp. 235: 116–125
Sherr CJ, DePinho RA . 2000 Cell 102: 407–410
Shore D . 1997 Trends Biochem. Sci. 22: 233–235
Smith S, Giriat I, Schmitt A, de Lange T . 1998 Science 282: 1484–1487
Smith S, de Lange T . 1999 J. Cell Sci. 112: 3649–3656
Smith GC, Jackson SP . 1999 Genes Dev. 13: 916–934
Song K, Jung D, Jung Y, Lee SG, Lee I . 2000 FEBS Lett. 48: 81–85
Vaziri H, Benchimol S . 1998 Curr. Biol. 8: 279–282
Vaziri H, Squire JA, Pandita TK, Bradley G, Kuba RM, Zhang H, Gulyas S, Hill RP, Nolan GP, Benchimol S . 1999 Mol. Cell. Biol. 19: 2373–2379
van Steensel B, Smogorzewska A, de Lange T . 1998 Cell 92: 410–413
Wei S, Wei S, Sedivy JM . 1999 Cancer Res. 59: 1539–1543
Wellinger RJ, Sen D . 1997 Eur. J. Cancer 33: 735–749
Weng NP, Levine BL, June C, Hodes RJ . 1996 J. Exp. Med. 183: 2471–2479
Wright WE, Shay JW . 1996 Modern Cell Biology Series–Cellular Aging and Cell Death. Holbrook NJ, Martin GR, Lockshin RA, (eds) Wiley & Sons, NY pp 153–167
Wright WE, Shay JW . 2000 Nature Med. 6: 849–851
Wu G, Lee WH, Chen PL . 2000 J. Biol. Chem. 275: 30618–30622
Yang J, Chang E, Cherry AM, Bangs CD, Oei Y, Bodnar A, Bronstein A, Chiu CP, Herron GS . 1999 J. Biol. Chem. 274: 26141–26148
Yang L, Suwa T, Wright WE, Shay JW, Hornsby PJ . 2001 Mech. Ageing Dev. 122: 1685–1694
Zhang X, Mar V, Zhou W, Harrrington L, Robinson MO . 1999 Genes Dev. 13: 2388–2399
Zhu L, Hathcock KS, Hande P, Lansdorp PM, Seldin MF, Hodes RJ . 1998 Proc. Natl. Acad. Sci. USA 95: 8648–8653
Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T . 2000 Nat. Genet. 25: 347–352
Acknowledgements
We thank present and past members of our laboratory for their hard work and stimulating discussions, our many colleagues and collaborators for generously sharing their reagents and ideas, and the National Institute on Aging, Ellison Medical Foundation, California Breast Cancer Research Program, and Department of Energy for research support.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, Sh., Kaminker, P. & Campisi, J. Telomeres, aging and cancer: In search of a happy ending. Oncogene 21, 503–511 (2002). https://doi.org/10.1038/sj.onc.1205077
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205077
Keywords
This article is cited by
-
Balancing self-renewal against genome preservation in stem cells: How do they manage to have the cake and eat it too?
Cellular and Molecular Life Sciences (2016)
-
Population-specific association of genes for telomere-associated proteins with longevity in an Italian population
Biogerontology (2015)