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The programmed aging paradigm: How we get old

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Abstract

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.

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References

  1. Goldsmith, T. (2013) The Evolution of Aging, 3rd Edn., Azinet Press, USA.

    Google Scholar 

  2. Kirkwood, T. B. L., and Austad, S. N. (2000) Why do we age? Nature, 408, 233–238.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  5. Libertini, G. (2012) Classification of phenoptotic phenomena, Biochemistry (Moscow), 77, 707–715.

    Article  CAS  Google Scholar 

  6. Finch, C. E. (1990) Longevity, Senescence and the Genome, University of Chicago Press, London.

    Google Scholar 

  7. Skulachev, V. P. (2002) Programmed death phenomena: from organelle to organism, Ann. N. Y. Acad. Sci., 959, 214–237.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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. Reed, J. C. (1999) Dysregulation of apoptosis in cancer, J. Clin. Oncol., 17, 2941–2953.

    PubMed  CAS  Google Scholar 

  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. Anversa, P., Kajstura, J., Leri, A., and Bolli, R. (2006) Life and death of cardiac stem cells, Circulation, 113, 1451–1463.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  15. Hayflick, L., and Moorhead, P. S. (1961) The serial cultivation of human diploid cell strains, Exp. Cell Res., 25, 585–621.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  19. Greider, C. W., and Blackburn, E. H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts, Cell, 51, 405–413.

    Article  Google Scholar 

  20. Van Steensel, B., and de Lange, T. (1997) Control of telomere length by the human telomeric protein TRF1, Nature, 385, 740–743.

    Article  PubMed  Google Scholar 

  21. Blackburn, E. H. (2000) Telomere states and cell fates, Nature, 408, 53–56.

    Article  PubMed  CAS  Google Scholar 

  22. Fossel, M. B. (2004) Cells, Aging and Human Disease, Oxford University Press, New York.

    Google Scholar 

  23. Ben-Porath, I., and Weinberg, R. (2005) The signals and pathways activating cellular senescence, Int. J. Biochem. Cell. Biol., 37, 961–976.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  28. De Lange, T., and Jacks, T. (1999) For better or worse? Telomerase inhibition and cancer, Cell, 98, 273–275.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. DePinho, R. A. (2000) The age of cancer, Nature, 408, 248–254.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

  35. Weir, M. R. (2007) Effects of rennin-angiotensin system inhibition on end-organ protection: can we do better? Clin. Ther., 29, 1803–1824.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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. 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. 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. 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. MacGregor, R. R., and Shalit, M. (1990) Neutrophil function in healthy elderly subjects, J. Gerontol., 45, M55-60.

  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.

    PubMed  CAS  PubMed Central  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  52. Geiger, H., and Van Zant, G. (2002) The aging of lymphohematopoietic stem cells, Nat. Immunol., 3, 329–333.

    Article  PubMed  CAS  Google Scholar 

  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. 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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Adams, V., Gielen, S., Hambrecht, R., and Schuler, G. (2001) Apoptosis in skeletal muscle, Front. Biosci., 6, D1–D11.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  71. Artandi, S. E. (2002) Telomere shortening and cell fates in mouse models of neoplasia, Trends Mol. Med., 8, 44–47.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  73. Bonner-Weir, S. (2000) Islet growth and development in the adult, J. Mol. Endocrinol., 24, 297–302.

    Article  PubMed  CAS  Google Scholar 

  74. Cerasi, E., Kaiser, N., and Leibowitz, G. (2000) Type 2 diabetes and beta cell apoptosis, Diabetes Metab., 26, 13–16.

    PubMed  CAS  Google Scholar 

  75. Martin, G. M., and Oshima, J. (2000) Lessons from human progeroid syndromes, Nature, 408, 263–266.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  78. Ostergren, J. (2007) Renin-angiotensin system blockade in the prevention of diabetes, Diabetes Res. Clin. Pract., 78, S13-21.

  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. Francis, R. M. (1998) Metabolic bone disease, in Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 5th Edn., pp. 1137–1154.

    Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. Weir, M. R. (2007) Microalbuminuria and cardiovascular disease, Clin. J. Am. Soc. Nephrol., 2, 581–590.

    Article  PubMed  Google Scholar 

  86. Berger, J. W., Fine, S. L., and Maguire, M. G. (1999) Age-Related Macular Degeneration, Mosby, St. Louis, USA.

    Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Fossel, M. B. (1996) Reversing Human Aging, William Morrow and Company, New York.

    Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  95. Gorelick, P. B. (2004) Risk factors for vascular dementia and Alzheimer disease, Stroke, 35, 2620–2622.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  97. Klein, B. E., Klein, R., Lee, K. E., and Grady, L. M. (2006) Statin use and incident nuclear cataract, JAMA, 295, 2752–2758.

    Article  PubMed  CAS  Google Scholar 

  98. Marciniak, R., and Guarente, L. (2001) Human genetics. Testing telomerases, Nature, 413, 370–372.

    Article  PubMed  CAS  Google Scholar 

  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. Weismann, A. (1892) Essays upon Heredity and Kindred Biological Problems, Vol. II, Clarendon Press, Oxford.

    Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  102. Szilard, L. (1959) On the nature of the aging process, Proc. Natl. Acad. Sci. USA, 45, 30–45.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  103. Skulachev, V. P. (2012) What is “phenoptosis” and how to fight it? Biochemistry (Moscow), 77, 827–846.

    Article  CAS  Google Scholar 

  104. Campisi, J. (1997) The biology of replicative senescence, Eur. J. Cancer, 33, 703–709.

    Article  PubMed  CAS  Google Scholar 

  105. Wright, W. E., and Shay, J. W. (2005) Telomere biology in aging and cancer, J. Am. Geriatr. Soc., 53, S292-294.

  106. Libertini, G. (2013) Evidence for aging theories from the study of a Hunter-Gatherer people (Ache of Paraguay), Biochemistry (Moscow), 78, 1023–1032.

    Article  CAS  Google Scholar 

  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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  1. Biochemistry (Moscow) Office, Maronovsky Pereulok 26, 119049, Moscow, Russia

    Giacinto Libertini

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Published in Russian in Biokhimiya, 2014, Vol. 79, No. 10, pp. 1237–1251.

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Libertini, G. The programmed aging paradigm: How we get old. Biochemistry Moscow 79, 1004–1016 (2014). https://doi.org/10.1134/S0006297914100034

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