Biochemistry (Moscow)

, Volume 79, Issue 10, pp 1004–1016 | Cite as

The programmed aging paradigm: How we get old

  • Giacinto LibertiniEmail author


According to the traditional explanations (“old paradigm”), aging is due to the progressive accumulation of heterogeneous damages that are insufficiently contrasted by natural selection. An opposite interpretation (“new paradigm”) sees aging as selectively advantageous in terms of supra-individual natural selection, and this implies the indispensable existence of genetically controlled specific mechanisms that determine it. The aim of this work is to expound synthetically the progressive alterations that mark the aging by showing how these changes are clearly defined and regulated by genes. The possibility of such a description, based on sound evidence, is an essential element for the plausibility of the new paradigm, and a fundamental argument against the tenability of the old paradigm.

Key words

aging phenoptosis programmed aging paradigm non-programmed aging paradigm cell turnover cell senescence Alzheimer ARMD 


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  1. 1.
    Goldsmith, T. (2013) The Evolution of Aging, 3rd Edn., Azinet Press, USA.Google Scholar
  2. 2.
    Kirkwood, T. B. L., and Austad, S. N. (2000) Why do we age? Nature, 408, 233–238.PubMedCrossRefGoogle Scholar
  3. 3.
    Libertini, G. (1988) An adaptive theory of the increasing mortality with increasing chronological age in populations in the wild, J. Theor. Biol., 132, 145–162.PubMedCrossRefGoogle Scholar
  4. 4.
    Skulachev, V. P. (1997) Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann’s hypothesis, Biochemistry (Moscow), 62, 1191–1195.Google Scholar
  5. 5.
    Libertini, G. (2012) Classification of phenoptotic phenomena, Biochemistry (Moscow), 77, 707–715.CrossRefGoogle Scholar
  6. 6.
    Finch, C. E. (1990) Longevity, Senescence and the Genome, University of Chicago Press, London.Google Scholar
  7. 7.
    Skulachev, V. P. (2002) Programmed death phenomena: from organelle to organism, Ann. N. Y. Acad. Sci., 959, 214–237.PubMedCrossRefGoogle Scholar
  8. 8.
    Libertini, G. (2008) Empirical evidence for various evolutionary hypotheses on species demonstrating increasing mortality with increasing chronological age in the wild, Sci. World J., 8, 183–193.CrossRefGoogle Scholar
  9. 9.
    Kerr, J. F. R., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics, Br. J. Cancer, 26, 239–257.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Libertini, G. (2009) The role of telomere-telomerase system in age-related fitness decline, a tameable process, in Telomeres: Function, Shortening and Lengthening (Mancini, L., ed.) Nova Science Publishers, New York, pp. 77–132.Google Scholar
  11. 11.
    Reed, J. C. (1999) Dysregulation of apoptosis in cancer, J. Clin. Oncol., 17, 2941–2953.PubMedGoogle Scholar
  12. 12.
    Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (eds.) (2013) Essential Cell Biology, 4th Edn., Garland Science, New York.Google Scholar
  13. 13.
    Anversa, P., Kajstura, J., Leri, A., and Bolli, R. (2006) Life and death of cardiac stem cells, Circulation, 113, 1451–1463.PubMedCrossRefGoogle Scholar
  14. 14.
    Richardson, B. R., Allan, D. S., and Le, Y. (2014) Greater organ involution in highly proliferative tissues associated with the early onset and acceleration of ageing in humans, Exp. Gerontol., 55, 80–91.PubMedCrossRefGoogle Scholar
  15. 15.
    Hayflick, L., and Moorhead, P. S. (1961) The serial cultivation of human diploid cell strains, Exp. Cell Res., 25, 585–621.PubMedCrossRefGoogle Scholar
  16. 16.
    Olovnikov, A. M. (1973) A theory of marginotomy: the incomplete copying of template margin in enzyme synthesis of polynucleotides and biological significance of the problem, J. Theor. Biol., 41, 181–190.PubMedCrossRefGoogle Scholar
  17. 17.
    Takubo, K., Aida, J., Izumiyama-Shimomura, N., Ishikawa, N., Sawabe, M., Kurabayashi, R., Shiraishi, H., Arai, T., and Nakamura, K-I. (2010) Changes of telomere length with aging, Geriatr. Gerontol. Int., 10, S197–206.PubMedCrossRefGoogle Scholar
  18. 18.
    Blackburn, E. H., and Gall, J. G. (1978) A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena, J. Mol. Biol., 120, 33–53.PubMedCrossRefGoogle Scholar
  19. 19.
    Greider, C. W., and Blackburn, E. H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts, Cell, 51, 405–413.CrossRefGoogle Scholar
  20. 20.
    Van Steensel, B., and de Lange, T. (1997) Control of telomere length by the human telomeric protein TRF1, Nature, 385, 740–743.PubMedCrossRefGoogle Scholar
  21. 21.
    Blackburn, E. H. (2000) Telomere states and cell fates, Nature, 408, 53–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Fossel, M. B. (2004) Cells, Aging and Human Disease, Oxford University Press, New York.Google Scholar
  23. 23.
    Ben-Porath, I., and Weinberg, R. (2005) The signals and pathways activating cellular senescence, Int. J. Biochem. Cell. Biol., 37, 961–976.PubMedCrossRefGoogle Scholar
  24. 24.
    Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., and Wright, W. E. (1998) Extension of lifespan by introduction of telomerase into normal human cells, Science, 279, 349–352.PubMedCrossRefGoogle Scholar
  25. 25.
    Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., and Weinberg, R. A. (1998) Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization, Proc. Natl. Acad. Sci. USA, 95, 14723–14728.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Vaziri, H. (1998) Extension of life span in normal human cells by telomerase activation: a revolution in cultural senescence, J. Anti-Aging Med., 1, 125–130.CrossRefGoogle Scholar
  27. 27.
    Vaziri, H., and Benchimol, S. (1998) Reconstitution of telomerase activity in normal cells leads to elongation of telomeres and extended replicative life span, Curr. Biol., 8, 279–282.PubMedCrossRefGoogle Scholar
  28. 28.
    De Lange, T., and Jacks, T. (1999) For better or worse? Telomerase inhibition and cancer, Cell, 98, 273–275.PubMedCrossRefGoogle Scholar
  29. 29.
    Jaskelioff, M., Muller, F. L., Paik, J. H., Thomas, E., Jiang, S., Adams, A. C., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadinanos, J., Horner, J. W., Maratos-Flier, E., and Depinho, R. A. (2011) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice, Nature, 469, 102–106.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    DePinho, R. A. (2000) The age of cancer, Nature, 408, 248–254.PubMedCrossRefGoogle Scholar
  31. 31.
    Hill, J. M., Zalos, G., Halcox, J. P. J., Schenke, W. H., Waclawiw, M. A., Quyyumi, A. A., and Finkel, T. (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk, N. Engl. J. Med., 348, 593–600.PubMedCrossRefGoogle Scholar
  32. 32.
    Werner, N., Kosiol, S., Schiegl, T., Ahlers, P., Walenta, K., Link, A., Bohm, M., and Nickenig, G. (2005) Circulating endothelial progenitor cells and cardiovascular outcomes, N. Engl. J. Med., 353, 999–1007.PubMedCrossRefGoogle Scholar
  33. 33.
    Tallis, R. C., Fillit, H. M., and Brocklehurst, J. C. (eds.) (1998) Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., Churchill Livingstone, New York.Google Scholar
  34. 34.
    Davidson, M. H. (2007) Overview of prevention and treatment of atherosclerosis with lipid-altering therapy for pharmacy directors, Am. J. Manag. Care, 13, S260-269.Google Scholar
  35. 35.
    Weir, M. R. (2007) Effects of rennin-angiotensin system inhibition on end-organ protection: can we do better? Clin. Ther., 29, 1803–1824.PubMedCrossRefGoogle Scholar
  36. 36.
    Urbanek, K., Quaini, F., Tasca, G., Torella, D., Castaldo, C., Nadal-Ginard, B., Leri, A., Kajstura, J., Quaini, E., and Anversa, P. (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy, Proc. Natl. Acad. Sci. USA, 100, 10440–10445.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Leri, A., Barlucchi, L., Limana, F., Deptala, A., Darzynkiewicz, Z., Hintze, T. H., Kajstura, J., Nadal-Ginard, B., and Anversa, P. (2001) Telomerase expression and activity are coupled with myocyte proliferation and preservation of telomeric length in the failing heart, Proc. Natl. Acad. Sci. USA, 98, 8626–8631.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Chimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., Di Meglio, F., Nadal-Ginard, B., Frustaci, A., Leri, A., Maseri, A., and Anversa, P. (2003) Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure, Circ. Res., 93, 604–613.PubMedCrossRefGoogle Scholar
  39. 39.
    Olivetti, G., Melissari, M., Capasso, J. M., and Anversa, P. (1991) Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy, Circ. Res., 68, 1560–1568.PubMedCrossRefGoogle Scholar
  40. 40.
    Aronow, W. S. (1998) Effects of aging on the heart, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 255–262.Google Scholar
  41. 41.
    Caird, F. I., and Dall, J. L. C. (1978) The cardiovascular system, in Textbook of Geriatric Medicine and Gerontology (Brocklehurst, J. C., ed.) 2nd Edn., Churchill Livingstone, New York, pp. 125–157.Google Scholar
  42. 42.
    Jibrini, M. B., Molnar, J., and Arora, R. R. (2008) Prevention of atrial fibrillation by way of abrogation of the rennin-angiotensin system: a systematic review and metaanalysis, Am. J. Ther., 15, 36–43.PubMedCrossRefGoogle Scholar
  43. 43.
    Fauchier, L., Pierre, B., de Labriolle, A., Grimard, C., Zannad, N., and Babuty, D. (2008) Anti-arrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trials, J. Am. Coll. Cardiol., 51, 828–835.PubMedCrossRefGoogle Scholar
  44. 44.
    Griffiths, C. E. M. (1998) Aging of the skin, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1293–1298.Google Scholar
  45. 45.
    Brodie, S. E. (1998) Aging and disorders of the eye, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 659–672.Google Scholar
  46. 46.
    Devlin, H., and Ferguson, M. W. J. (1998) Aging and the orofacial tissues, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 789–802.Google Scholar
  47. 47.
    Reinus, J. F., and Brandt, L. J. (1998) The upper gastrointestinal tract, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 803–826.Google Scholar
  48. 48.
    Gilleece, M. H., and Dexter, T. M. (1998) Aging and the blood, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1241–1246.Google Scholar
  49. 49.
    MacGregor, R. R., and Shalit, M. (1990) Neutrophil function in healthy elderly subjects, J. Gerontol., 45, M55-60.Google Scholar
  50. 50.
    Schwab, R., Hausman, P. B., Rinnooy-Kan, E., and Weksler, M. E. (1985) Immunological studies of ageing. X. Impaired T lymphocytes and normal monocyte response from elderly humans to the mitogenic antibodies OKT3 and Leu4, Immunology, 55, 677–684.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Murasko, D. M., Nelson, B. J., Silver, R., Matour, D., and Kaye, D. (1986) Immunologic response in an elderly population with a mean age of 85, Am. J. Med., 81, 612–618.PubMedCrossRefGoogle Scholar
  52. 52.
    Geiger, H., and Van Zant, G. (2002) The aging of lymphohematopoietic stem cells, Nat. Immunol., 3, 329–333.PubMedCrossRefGoogle Scholar
  53. 53.
    Webster, S. G. P. (1978) The gastrointestinal system — c. The pancreas and the small bowel, in Textbook of Geriatric Medicine and Gerontology (Brocklehurst, J. C., ed.) 2nd Edn., Churchill Livingstone, New York, pp. 358–368.Google Scholar
  54. 54.
    Baime, M. J., Nelson, J. B., and Castell, D. O. (1994) Aging of the gastrointestinal system, in Principles of Geriatric Medicine and Gerontology (Hazzard, W. R., et al., eds.) 3rd Edn., McGraw-Hill, New York, pp. 665–681.Google Scholar
  55. 55.
    Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., and Clevers, H. (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5, Nature, 449, 1003–1007.PubMedCrossRefGoogle Scholar
  56. 56.
    Grimby, G., Danneskiold-Samsoe, B., Hvid, K., and Saltin, B. (1982) Morphology and enzymatic capacity in arm and leg muscles in 78-81 year old men and women, Acta Physiol. Scand., 115, 125–134.PubMedCrossRefGoogle Scholar
  57. 57.
    Lexell, J., Taylor, C. C., and Sjostrom, M. (1988) What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men, J. Neurol. Sci., 84, 275–294.PubMedCrossRefGoogle Scholar
  58. 58.
    Cumming, W. J. K. (1998) Aging and neuromuscular disease, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1115–1130.Google Scholar
  59. 59.
    Adams, V., Gielen, S., Hambrecht, R., and Schuler, G. (2001) Apoptosis in skeletal muscle, Front. Biosci., 6, D1–D11.PubMedCrossRefGoogle Scholar
  60. 60.
    Young, A., Stokes, M., and Crowe, M. (1984) Size and strength of the quadriceps muscles of old and young women, Eur. J. Clin. Invest., 14, 282–287.PubMedCrossRefGoogle Scholar
  61. 61.
    Young, A., Stokes, M., and Crowe, M. (1985) The size and strength of the quadriceps muscles of old and young men, Clin. Physiol., 5, 145–154.PubMedCrossRefGoogle Scholar
  62. 62.
    Vandervoort, A. A., and McComas, A. J. (1986) Contractile changes in opposing muscles of the human ankle joint with aging, J. Appl. Physiol., 61, 361–367.PubMedGoogle Scholar
  63. 63.
    Davies, C. T. M., Thomas, D. O., and White, M. J. (1986) Mechanical properties of young and elderly human muscle, Acta Med. Scand., 711, S219–226.Google Scholar
  64. 64.
    Klitgaard, H., Mantoni, M., Schiaffino, S., Ausoni, S., Gorza, L., Laurent-Winter, C., Schnohr, P., and Saltin, B. (1990) Function, morphology and protein expression of ageing skeletal muscle: a cross-sectional study of elderly men with different training backgrounds, Acta Physiol. Scand., 140, 41–54.PubMedCrossRefGoogle Scholar
  65. 65.
    Rutherford, O. M., and Jones, D. A. (1992) The relationship of muscle and bone loss and activity levels with age in women, Age Ageing, 21, 286–293.PubMedCrossRefGoogle Scholar
  66. 66.
    Philips, S. K., Bruce, S. A., Newton, D., and Woledge, R. C. (1992) The weakness of old age is not due to failure of muscle activation, J. Gerontol. Med. Sci., 47, M45-49.Google Scholar
  67. 67.
    Marchesini, G., Bua, V., Brunori, A., Bianchi, G., Pisi, P., Fabbri, A., Zoli, M., and Pisi, E. (1988) Galactose elimination capacity and liver volume in aging man, Hepatology, 8, 1079–1083.PubMedCrossRefGoogle Scholar
  68. 68.
    Wynne, H. A., Cope, L. H., Mutch, E., Rawlins, M. D., Woodhouse, K. W., and James, O. F. (1989) The effect of age upon liver volume and apparent liver blood flow in healthy man, Hepatology, 9, 297–301.PubMedCrossRefGoogle Scholar
  69. 69.
    David, H., and Reinke, P. (1988) Liver morphology with aging, in Aging in Liver and Gastrointestinal Tracts (Bianchi, L., Holt, P., and James, O. F. W., eds.) MTP Press, Lancaster (UK), pp. 143–159.Google Scholar
  70. 70.
    Watanabe, T., and Tanaka, Y. (1982) Age-related alterations in the size of human epatocytes: study of mononuclear and binuclear cells, Virchow Arch., 39, 9–20.CrossRefGoogle Scholar
  71. 71.
    Artandi, S. E. (2002) Telomere shortening and cell fates in mouse models of neoplasia, Trends Mol. Med., 8, 44–47.PubMedCrossRefGoogle Scholar
  72. 72.
    Finegood, D. T., Scaglia, L., and Bonner-Weir, S. (1995) Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model, Diabetes, 44, 249–256.PubMedCrossRefGoogle Scholar
  73. 73.
    Bonner-Weir, S. (2000) Islet growth and development in the adult, J. Mol. Endocrinol., 24, 297–302.PubMedCrossRefGoogle Scholar
  74. 74.
    Cerasi, E., Kaiser, N., and Leibowitz, G. (2000) Type 2 diabetes and beta cell apoptosis, Diabetes Metab., 26, 13–16.PubMedGoogle Scholar
  75. 75.
    Martin, G. M., and Oshima, J. (2000) Lessons from human progeroid syndromes, Nature, 408, 263–266.PubMedCrossRefGoogle Scholar
  76. 76.
    Harris, M. I., Hadden, W. C., Knowler, W. C., and Bennett, P. H. (1987) Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr, Diabetes, 36, 523–534.PubMedCrossRefGoogle Scholar
  77. 77.
    McCall, K. L., Craddock, D., and Edwards, K. (2006) Effect of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on the rate of new-onset diabetes mellitus: a review and pooled analysis, Pharmacotherapy, 26, 1297–1306.PubMedCrossRefGoogle Scholar
  78. 78.
    Ostergren, J. (2007) Renin-angiotensin system blockade in the prevention of diabetes, Diabetes Res. Clin. Pract., 78, S13-21.Google Scholar
  79. 79.
    Dieppe, P., and Tobias, J. (1998) Bone and joint aging, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1131–1136.Google Scholar
  80. 80.
    Francis, R. M. (1998) Metabolic bone disease, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1137–1154.Google Scholar
  81. 81.
    Connolly, M. J. (1998) Age-related changes in the respiratory system, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1073–1078.Google Scholar
  82. 82.
    Enright, P. L., Kronmal, R. A., Higgins, M., Schenker, M., and Haponik, E. F. (1993) Spirometry reference values for women and men 65 to 85 years of age. Cardiovascular health study, Am. Rev. Respir. Dis., 147, 125–133.PubMedCrossRefGoogle Scholar
  83. 83.
    Alexeeff, S. E., Litonjua, A. A., Sparrow, D., Vokonas, P. S., and Schwartz, J. (2007) Statin use reduces decline in lung function, Am. J. Respir. Crit. Care Med., 176, 742–747.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Jassal, V., Fillit, H., and Oreopoulos, D. G. (1998) Aging of the urinary tract, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 919–924.Google Scholar
  85. 85.
    Weir, M. R. (2007) Microalbuminuria and cardiovascular disease, Clin. J. Am. Soc. Nephrol., 2, 581–590.PubMedCrossRefGoogle Scholar
  86. 86.
    Berger, J. W., Fine, S. L., and Maguire, M. G. (1999) Age-Related Macular Degeneration, Mosby, St. Louis, USA.Google Scholar
  87. 87.
    Fine, S. L., Berger, J. W., Maguire, M. G., and Ho, A. C. (2000) Age-related macular degeneration, N. Engl. J. Med., 342, 483–492.PubMedCrossRefGoogle Scholar
  88. 88.
    Klein, R., Deng, Y., Klein, B. E., Hyman, L., Seddon, J., Frank, R. N., Wallace, R. B., Hendrix, S. L., Kuppermann, B. D., Langer, R. D., Kuller, L., Brunner, R., Johnson, K. C., Thomas, A. M., and Haan, M. (2007) Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: women’s health initiative sight exam ancillary study, Am. J. Ophthalmol., 143, 473–483.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Fossel, M. B. (1996) Reversing Human Aging, William Morrow and Company, New York.Google Scholar
  90. 90.
    Flanary, B. (2009) Telomeres: function, shortening, and lengthening, in Telomeres: Function, Shortening and Lengthening (Mancini, L., ed.) Nova Science Publishers, New York, pp. 431–438.Google Scholar
  91. 91.
    Qiu, W. Q., Walsh, D. M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M. B., Rosner, M. R., Safavi, A., Hersh, L. B., and Selkoe, D. J. (1998) Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation, J. Biol. Chem., 273, 32730–32738.PubMedCrossRefGoogle Scholar
  92. 92.
    Vekrellis, K., Ye, Z., Qiu, W. Q., Walsh, D., Hartley, D., Chesneau, V., Rosner, M. R., and Selkoe, D. J. (2000) Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme, J. Neurosci., 20, 1657–1665.PubMedGoogle Scholar
  93. 93.
    Bertram, L., Blacker, D., Mullin, K., Keeney, D., Jones, J., Basu, S., Yhu, S., McInnis, M. G., Go, R. C., Vekrellis, K., Selkoe, D. J., Saunders, A. J., and Tanzi, R. E. (2000) Evidence for genetic linkage of Alzheimer’s disease to chromosome 10q, Science, 290, 2302–2303.PubMedCrossRefGoogle Scholar
  94. 94.
    Von Zglinicki, T., Serra, V., Lorenz, M., Saretzki, G., Lenzen-Grossimlighaus, R., Gessner, R., Risch, A., and Steinhagen-Thiessen, E. (2000) Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? Lab. Invest., 80, 1739–1747.CrossRefGoogle Scholar
  95. 95.
    Gorelick, P. B. (2004) Risk factors for vascular dementia and Alzheimer disease, Stroke, 35, 2620–2622.PubMedCrossRefGoogle Scholar
  96. 96.
    Tassin, J., Malaise, E., and Courtois, Y. (1979) Human lens cells have an in vitro proliferative capacity inversely proportional to the donor age, Exp. Cell Res., 123, 388–392.PubMedCrossRefGoogle Scholar
  97. 97.
    Klein, B. E., Klein, R., Lee, K. E., and Grady, L. M. (2006) Statin use and incident nuclear cataract, JAMA, 295, 2752–2758.PubMedCrossRefGoogle Scholar
  98. 98.
    Marciniak, R., and Guarente, L. (2001) Human genetics. Testing telomerases, Nature, 413, 370–372.PubMedCrossRefGoogle Scholar
  99. 99.
    Fillit, H. M., Rockwood, K., and Woodhouse, K. (eds.) (2010) Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 7th Edn., Saunders Elsevier, Philadelphia.Google Scholar
  100. 100.
    Weismann, A. (1892) Essays upon Heredity and Kindred Biological Problems, Vol. II, Clarendon Press, Oxford.Google Scholar
  101. 101.
    Kirkwood, T. B. L., and Cremer, T. (1982) Cytogerontology since 1881: a reappraisal of August Weissmann and a review of modern progress, Hum. Genet., 60, 101–121.PubMedCrossRefGoogle Scholar
  102. 102.
    Szilard, L. (1959) On the nature of the aging process, Proc. Natl. Acad. Sci. USA, 45, 30–45.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Skulachev, V. P. (2012) What is “phenoptosis” and how to fight it? Biochemistry (Moscow), 77, 827–846.CrossRefGoogle Scholar
  104. 104.
    Campisi, J. (1997) The biology of replicative senescence, Eur. J. Cancer, 33, 703–709.PubMedCrossRefGoogle Scholar
  105. 105.
    Wright, W. E., and Shay, J. W. (2005) Telomere biology in aging and cancer, J. Am. Geriatr. Soc., 53, S292-294.Google Scholar
  106. 106.
    Libertini, G. (2013) Evidence for aging theories from the study of a Hunter-Gatherer people (Ache of Paraguay), Biochemistry (Moscow), 78, 1023–1032.CrossRefGoogle Scholar
  107. 107.
    Libertini, G. (2009) Prospects of a longer life span beyond the beneficial effects of a healthy lifestyle, in Handbook on Longevity: Genetics, Diet & Disease (Bentely, J. V., and Keller, M. A., eds.) Nova Science Publishers, New York, pp. 35–95.Google Scholar

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© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Biochemistry (Moscow) OfficeMoscowRussia

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