Skip to main content
SpringerLink
Log in

Telomere shortening: The main mechanism of natural and radiation aging

  • Radiobiology and Radioecology
  • Published:
Biophysics Aims and scope Submit manuscript

Abstract

We present evidence that telomere shortening is the main or even sole mechanism of natural and radiation aging. All apparent contradictions, primarily, the absence of exact inverse correlation between residual telomere length and donor age, are explained using telomere theory. We try to explain in how telomere shortening might be the cause of aging and longevity limitation. We also show the inability of oxidative theory to explain a number of indisputable facts easily explained by telomere theory, such as unlimited growth of tumor cells or why a newborn child starts to age from zero level rather than the level reached by the cells of his parents at the moment of conception. We postulate that if oxidative damage were entirely absent, telomeres would nevertheless shorten with each mitotic cycle, because such is the mechanism of DNA replication, and aging would progress, which we invariantly observe in the presence of any antioxidants. However, if telomeres do not shorten, as happens in transformed cells because telomerase works there, aging does cease and the transformed cells show no senescence. We also observe it in spite of the damaging effect of reactive oxygen species. which may be even more than in normal cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L. Hayflick and P. C. Moorhead, Exp. Cell. Res. 25, 585 (1961).

    Article  Google Scholar 

  2. A. M. Olovnikov, Dokl. Acad. Sci. 201(6), 1496 (1971).

    Google Scholar 

  3. A. M. Olovnikov, J. Theor. Biol. 41(1), 181 (1973).

    Article  Google Scholar 

  4. C. W. Greider and E. H. Blackburn, Cell 51(6), 887 (1987).

    Article  Google Scholar 

  5. A. G. Bodnar, M. Ouellette, M. Frolkis, et al., Science 279(5349), 349 (1998).

    Article  ADS  Google Scholar 

  6. K. M. Eisenhauer, R. M. Gerstain, C. P. Chiu, et al., Biol. Reprod. 56(5), 1120 (1997).

    Article  Google Scholar 

  7. R. C. Allsopp, H. Vaziri, C. Patterson, et al., Proc. Natl. Acad. Sci. USA 89(21), 10114 (1992).

    Article  ADS  Google Scholar 

  8. F. S. Wyllie, C. J. Jones, J.W. Skinner, et al., Nat. Genet. 24(1), 16 (2000).

    Article  Google Scholar 

  9. U. Herbig, M. Ferreira, L. Condel, et al., Science 311(5765), 1257 (2006).

    Article  Google Scholar 

  10. V. J. Cristofalo, R. G. Allen, R. J. Pignolo, et al., Proc. Natl. Acad. Sci. USA 95(18), 10614 (1998).

    Article  ADS  Google Scholar 

  11. V. J. Cristofalo, A. Lorenzini, and R. G. Allen, Mech. Aging Dev. 125(10–11), 827 (2004).

    Article  Google Scholar 

  12. C. Mondello, C. Petropoulou, D. Monti, et al., Exp Cell. Res. 248(1), 234 (1999).

    Article  Google Scholar 

  13. J. N. Buchholz, E. J. Behringer, W. J. Pottorf, et al., Aging Cell 6(3), 285 (2007).

    Article  Google Scholar 

  14. D. Harman, Gerontol. 11, 298 (1956).

    Google Scholar 

  15. L. Hayflick, Ann. N.Y. Acad. Sci. 1100, 1 (2007).

    Article  ADS  Google Scholar 

  16. A. M. Olovnikov, J. Alzheim. Dis. 11(2), 241 (2007).

    Google Scholar 

  17. S. R. Terlecky, J. L. Koepke, and P. A. Walton, Biochem. Biophys. Acta 1763(12), 1749 (2006).

    Article  Google Scholar 

  18. Y. Kim and H. Sun, Aging Cell 6(4), 489 (2007).

    Article  Google Scholar 

  19. V. N. Anisimov, L. E. Bakeeva, P. A. Egormin, et al., Biochem (Mosc) 73(12), 1329 (2008).

    Article  Google Scholar 

  20. V. M. Mikhelson, Mech. Ageing Dev. 122(13), 1361 (2001).

    Article  Google Scholar 

  21. G. Martin, C. Sprague, and C. Epstein, Lab. Invest. 23(1), 86 (1970).

    Google Scholar 

  22. T. H. Brummendorf, N. Rufer, T. L. Holyoake, et al., Ann. N.Y. Acad. Sci. 938, 293 (2001).

    Article  ADS  Google Scholar 

  23. O. T. Njajou, R. M. Cawthon, C. M. Damcott, et al., Proc. Natl. Acad. Sci. USA 104(29), 12135 (2007).

    Article  ADS  Google Scholar 

  24. J. Barwell, L. Pangon, A. Georgiou, et al., Br. J. Cancer 97(12), 1696 (2007).

    Article  Google Scholar 

  25. R. S. Maser and R. A. DePinho, DNA Repair (Amst.) 54(8–9), 480 (2004).

    Google Scholar 

  26. L. Freitag, P. Litterst, B. Obertrifter, et al., Pneumologie 54(11), 480 (2000).

    Article  Google Scholar 

  27. C. Frías, C. García-Aranda, C. De Juan, et al., Lung Cancer 60(3), 416 (2008).

    Article  Google Scholar 

  28. Z. Li, Z. H. Meng, A. Sayeed, et al., Cancer Res 62(20), 5980 (2002).

    Google Scholar 

  29. M. L. Dumble, E. J. Croager, G. C. Yeoh, and E. A. Quail, Carcinogenesis 23(3), 435 (2002).

    Article  Google Scholar 

  30. T. Kanamaru, K. Tanaka, J. Kotani, et al., Int. J. Mol. Med. 10(2), 205 (2002).

    Google Scholar 

  31. A. Ohali, S. Avigad, S. Ash, et al., Cancer 107(6), 1391 (2006).

    Article  Google Scholar 

  32. S. Avigad, I. Naumov, A. Ohali, et al., Clin. Cancer Res., 2007, vol. 13, no. 19, pp. 5777–5783.

    Article  Google Scholar 

  33. C. Martin-Ruiz, H. O. Dickinson, B. Keys, et al., Ann. Neurol. 60(2), 174 (2006).

    Article  Google Scholar 

  34. P. Zhang, C. Dilley, and M. P. Mattson, Neuroscience 145(4), 1439 (2007).

    Article  Google Scholar 

  35. A. Aviv, J. Mol. Med. 80(11), 689 (2002).

    Article  Google Scholar 

  36. Y. E. Yegorov, I. V. Semenova, D. N. Karachentsev, et al., Membr Cell Biol. 14(6), 855 (2001).

    Google Scholar 

  37. F. A. Goytisolo, E. Samper, S. Edmonson, et al., Mol Cell Biol. 21(11), 3642 (2001).

    Article  Google Scholar 

  38. M. A. Blasko, EMBO 24(6), 1095 (2005).

    Article  Google Scholar 

  39. M. T. Hemann and C. W. Greider, Nucleic Acids Res. 28(22), 4474 (2000).

    Article  Google Scholar 

  40. E. L. Manning, J. Crossland, M. J. Dewey, and G. Van Zant, Mamm Genome 13(5), 234 (2002).

    Article  Google Scholar 

  41. L. Y. Hao, M. Armanios, M. A. Strong, et al., Cell 123(6), 1121 (2005).

    Article  Google Scholar 

  42. I. A. Gamale@i, Yu. S. Polozov, K. M. Kirpichnikova, et al., Tsitologiya 43(7), 633 (2001).

    Google Scholar 

  43. C. Hwang, A. J. Sinskey, and H. F. Lodish, Science 257(5076), 1496 (1992).

    Article  ADS  Google Scholar 

  44. J. L. Martindale and N. J. Holbrook, J. Cell Physiol. 192(1), 1 (2002).

    Article  Google Scholar 

  45. C. Pantano, N. L. Reynaert, A. van der Vliet, and Y. M. Janssen-Heininger, Antioxid Redox Signal 8(9–10), 1791 (2006).

    Article  Google Scholar 

  46. G. N. Rao and B. C. Berk, Circ Res. 702(3), 593 (1992).

    ADS  Google Scholar 

  47. R. H. Burdon, D. Alliangana, and V. Gill, Free Radic Res. 23(5), 471 (1995).

    Article  Google Scholar 

  48. M. Sekharam, A. Trotti, J. M. Cunnick, and J. Wu, Toxicol Appl Pharmacol. 149(2), 210 (1998).

    Article  Google Scholar 

  49. I. A. Gamaley, N. D. Aksenov, T. N. Efremova, and K. M. Kirpichnikova, Tsitologiya 45(1), 26 (2003).

    Google Scholar 

  50. N. Li and T.D. Oberley, J. Cell Physiol. 177(1), 148 (1998).

    Article  Google Scholar 

  51. N. Li, T. D. Oberley, L. W. Oberley, and W. Zhong, J. Cell Physiol. 175(3), 359 (1998).

    Article  Google Scholar 

  52. N. Li, T. D. Oberley, L. W. Oberley, and W. Zhong, Prostate 35(3), 221 (1998).

    Article  Google Scholar 

  53. H. Sauer, G. Rahimi, J. Hescheler, and M. Wartenberg, FEBS Lett. 476(3), 218 (2000).

    Article  Google Scholar 

  54. H. Sauer, M. Wartenberg, and J. Hescheler, Cell Physiol. Biochem. 11(4), 173 (2001).

    Article  Google Scholar 

  55. N. R. Forsyth, A. P. Evans, J. W. Shay, and W. E. Wright, Aging Cell. 2(5), 235 (2003).

    Article  Google Scholar 

  56. Z. Spolarics and J. X. Wu, Am. J. Physiol. 273(6 Pt 1), G1304 (1997).

    Google Scholar 

  57. S. G. Rhee, Y. S. Bae, S. R. Lee, and J. Kwon, Sci STKE 2000(50), 1 (2000).

    Google Scholar 

  58. G. I. Giles, Curr Pharm Des. 12(34), 4427 (2006).

    Article  Google Scholar 

  59. I. A. Gamaley and I. V. Klyubin, Int Rev Cytol. 188, 203 (1999).

    Article  Google Scholar 

  60. T. A. Thompson, K. Kim, and M. N. Gould, Cancer Res. 58(22), 5097 (1998).

    Google Scholar 

  61. K. Irani and P. J. Goldschmidt-Clermont, Biochem. Pharmacol. 55(9), 1339 (1998).

    Article  Google Scholar 

  62. K. Irani, Y. Xia, J. L. Zweier, et al., Science 275(5306), 1649 (1997).

    Article  Google Scholar 

  63. H. Aebi, M. Cantz, and H. Suter, Experientia 21(12), 713 (1965).

    Article  Google Scholar 

  64. A. M. Baker, L. W. Oberley, and M. B. Cohen, Prostate 322(4), 229 (1997).

    Article  Google Scholar 

  65. I. Gamaley, T. Efremova, K. Kirpichnikova, et al., Cell Biol. Int. 30(4), 319 (2006).

    Article  Google Scholar 

  66. T. Palomares, A. Alonso-Varona, A. Alvarez, et al., Clin. Exp. Metastasis. 15(3), 329 (1997).

    Article  Google Scholar 

  67. Y. Calle, T. Palomares, B. Castro, et al., Chemotherapy 46(6), 408 (2000).

    Article  Google Scholar 

  68. R. G. Allen and A. K. Balin, Exp. Cell Res. 289(2), 307 (2003).

    Article  Google Scholar 

  69. A. K. Balin, L. Pratt, and R. G. Allen, Free Radic. Biol. Med. 32(3), 257 (2002).

    Article  Google Scholar 

  70. R. A. Bridges, H. Berendes, and R. A. Good, Am. J. Dis. Child. 97(4), 387 (1959).

    Google Scholar 

  71. B. L. Schapiro, P. E. Newburger, M. S. Klempner, and M. C. Dinauer, N. Engl. J. Med. 325(25), 1786 (1991).

    Article  Google Scholar 

  72. L. Góth, P. Rass, and A. Páy, Mol. Diagn. 8(3), 141 (2004).

    Article  Google Scholar 

  73. V. J. Cristofalo, A. Lorenzini, R. G. Allen, et al., Mech. Ageing. Dev. 125(10–11), 827 (2004).

    Article  Google Scholar 

  74. J. N. Buchholz, E. J. Behringer, and W. J. Pottorf, Aging Cell. 62(3), 285 (2007).

    Article  Google Scholar 

  75. T. von Zglinicki, G. Saretzki, W. Döcke, et al., Exp. Cell Res. 20(1), 186 (1995).

    Article  Google Scholar 

  76. T. von Zglinicki, R. Pilger, and N. Sitte, Free Radic. Biol. Med. 28(1), 64 (2000).

    Article  Google Scholar 

  77. T. von Zglinicki, Trends Biochem. Sci. 27(7), 339 (2002).

    Article  Google Scholar 

  78. J. F. Passos and T. von Zglinicki, Free Radic. Res. 40(12), 1277 (2006)

    Article  Google Scholar 

  79. J. F. Passos, G. Saretzki, and T. von Zglinicki, Nucleic Acids Res. 35(22), 7505 (2007).

    Article  Google Scholar 

  80. A. Ayouaz, C. Raynaud, C. Heride, et al., Biochimie 90(1), 60 (2008).

    Article  Google Scholar 

  81. J. P. Newman, B. Banerjee, W. Fang, et al., J. Cell Physiol. 214(3), 796 (2008).

    Article  Google Scholar 

  82. H. J. Curtis, Gerontologist 6(3), 143 (1966).

    Google Scholar 

  83. I. E. Vorobtsova and A. V. Semenov, Radiats Biol. Radioecol. 46(2), 140 (2006).

    Google Scholar 

  84. M. Castella, S. Puerto, A. Creus, et al., Toxicol. Lett. 172(1–2), 29 (2007).

    Article  Google Scholar 

  85. E. S. Epel, E. H. Blackburn, J. Lin, et al., Proc. Natl. Acad. Sci U S A. 101(49), 17312 (2004).

    Article  ADS  Google Scholar 

  86. E. S. Epel, J. Lin, F. H. Wilhelm, et al., Psychoneuroendocrinology 31(3), 277 (2006).

    Article  Google Scholar 

  87. S. Misri, S. Pandita, R. Kumar, and T. K. Pandita, Cytogenet Genome Res. 122(3–4), 297 (2008).

    Article  Google Scholar 

  88. A. Ayouaz, C. Raynaud, C. Heride, et al., Biochimie 90(1), 60 (2008).

    Article  Google Scholar 

  89. N. M. Emanuel and L. K. Obukhova, Exp. Gerontol. 13(1–2), 25 (1978).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia

    V. M. Mikhelson & I. A. Gamaley

Authors
  1. V. M. Mikhelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. A. Gamaley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. M. Mikhelson.

Additional information

Original Russian Text © V.M. Mikhelson, I.A. Gamaley, 2010, published in Radiatsionnaya Biologiya. Radioekologiya, 2010, Vol. 50, No. 3, pp. 269–275.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mikhelson, V.M., Gamaley, I.A. Telomere shortening: The main mechanism of natural and radiation aging. BIOPHYSICS 55, 848–853 (2010). https://doi.org/10.1134/S0006350910050295

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006350910050295

Keywords

Search

Navigation