БИОХИМИЯ, 2019, том 84, вып. 12, с. 1781–1791

УДК 577.24

Возрастные нарушения функций клеток, тканей и органов: доказательства их существования и их связь с факторами риска и защитными лекарствами

Обзор

© 2019 Г. Либертини 1*#, Г. Корби 2#, М. Челлурале 3, Н. Феррара 3

Independent researcher, Member of the Italian Society for Evolutionary Biology, Italy; E-mail: giacinto.libertini@yahoo.com

Department of Medicine and Health Sciences, University of Molise, and Italian Society of Gerontology and Geriatrics (SIGG), Campobasso, Italy; E-mail: graziamaria.corbi@unimol.it

Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy; E-mail: mikicellurale@alice.it, nicola.ferrara@unina.it

Поступила в редакцию 16.03.2019
После доработки 13.08.2019
Принята к публикации 23.08.2019

DOI: 10.1134/S0320972519120030

КЛЮЧЕВЫЕ СЛОВА: старение, теломера, субтеломера, парадигма программированного старения, парадигма непрограммированного старения, факторы риска, защитные лекарства.

Аннотация

Для теорий, которые интерпретируют биологическое старение как феномен, которому благоприятствует естественный отбор, необходимы доказательства существования специфических, генетически предопределенных и регулируемых механизмов, которые связаны с постепенным повышением смертности индивидов в связи с их возрастом. Механизмы, которые определены в соответствии с теорией субтеломеры–теломеры, предполагают, что постепенное ослабление процесса обновления клеток и снижение клеточных функций регулируются системой субтеломера–теломера–теломераза, которая вызывает прогрессирующий «синдром атрофии» во всех тканях и органах. Если  механизмы, лежащие в основе возрастных нарушений функций, действительно аналогичны друг другу, и имеют общее происхождение, можно предположить, что равные интервенции могут привести к получению сходных результатов. В настоящем обзоре рассмотрена роль отдельных факторов (сахарный диабет, ожирение/дислипидемия, повышенное давление, курение, умеренное потребление алкоголя или злоупотреблением им) и различных типов лекарств (статины, ингибиторы ACE/сартаны) в ускорении и предвкушении или в противостоянии процессу старения. Имеющиеся доказательства согласуются с парадигмой программированного старения и механизмами, определенными в рамках теории программированного старения. В то же время, нет очевидного определения, на основании которого можно будет проводить различия с теорией непрограммированного старения. Кроме того, существование механизмов, которые определяются системой субтеломера–теломера–теломераза, вызывающей постепенное возрастное снижение приспособленности (фитнеса) организма в связи с постепенным старением клеток и процесса клеточного старения, не оправдано без эволюционной мотивации. Их существование вполне ожидаемо в рамках парадигмы программированного старения, но не совместимо с противоположной парадигмой.

Сноски

* Адресат для корреспонденции.

# Авторы внесли равный вклад в работу.

Финансирование

Выполнение данной работы не было поддержено какими-либо грантами от фондов, финансирующих осуществление проектов в сфере общественных, коммерческих или некоммерческих организаций.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с использованием людей и животных в качестве объектов.

Список литературы

1. 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.

2. Finch, C.E. (1990) Longevity, senescence, and the genome, The University of Chicago Press, Chicago.

3. Hill, K., and Hurtado, A.M. (1996) Ache life history, Aldine De Gruyter, New York.

4. Ricklefs, R.E. (1998) Evolutionary theories of aging: confirmation of a fundamental prediction, with implications for the genetic basis and evolution of life span, Am. Nat., 152, 24–44.

5. Nussey, D.H., Froy, H., Lemaitre, J.F., Gaillard, J.M., and Austad, S.N. (2013) Senescence in natural populations of animals: widespread evidence and its implications for biogerontology, Ageing Res. Rev., 12, 214–225.

6. Medvedev, Z.A. (1990) An attempt at a rational classification of theories of ageing, Biol. Rev. Camb. Philos. Soc., 65, 375–398.

7. Libertini, G., Rengo, G., and Ferrara, N. (2017) Aging and aging theories, J. Gerontol. Geriatrics, 65, 59–77.

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, 182–193.

9. Libertini, G. (2015) Non-programmed versus programmed aging paradigm, Curr. Aging Sci., 8, 56–68.

10. Kuhn, T.S. (1962) The Structure of Scientific Revolutions, The University of Chicago Press, Chicago.

11. Hayflick, L. (2007) Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both, PLoS Genet., 3, 220, doi: 10.1371/journal.pgen.0030220.

12. Libertini, G. (2015) Phylogeny of aging and related phenoptotic phenomena, Biochemistry (Moscow), 80, 1529–1546.

13. Travis, J.M. (2004) The evolution of programmed death in a spatially structured population, J. Gerontol. A Biol. Sci. Med. Sci., 59, 301–305.

14. Skulachev, V.P., and Longo, V.D. (2005) Aging as a mitochondria-mediated atavistic program: can aging be switched off? Ann. N. Y. Acad. Sci., 1057, 145–164.

15. Martins, A.C. (2011) Change and aging senescence as an adaptation, PLoS One, 6, 24328, doi: 10.1371/journal.pone.0024328.

16. Yang, J-N. (2013) Viscous populations evolve altruistic programmed ageing in ability conflict in a changing environment, Evol. Ecol. Res., 15, 527–543.

17. Mitteldorf, J., and Martins, A.C. (2014) Programmed life span in the context of evolvability, Am. Nat., 184, 289–302.

18. Skulachev, V.P. (1999) Phenoptosis: programmed death of an organism, Biochemistry (Moscow), 64, 1418–1426.

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

20. Olshansky, S.J., Hayflick, L., and Carnes, B.A. (2002) Position statement on human aging, J. Gerontol. A Biol. Sci. Med. Sci., 57, 292–297.

21. Hayflick, L. (2007) Biological aging is no longer an unsolved problem, Ann. N. Y. Acad. Sci., 1100, 1–13.

22. Kirkwood, T.B., and Melov, S. (2011) On the programmed/non-programmed nature of ageing within the life history, Curr. Biol., 21, 701–707.

23. De Grey, A.D. (2015) Do we have genes that exist to hasten aging? New data, new arguments, but the answer is still no, Curr. Aging Sci., 8, 24–33.

24. Gladyshev, V.N. (2016) Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes, Aging Cell, 15, 594–602.

25. Kowald, A., and Kirkwood, T.B. (2016) Can aging be programmed? A critical literature review, Aging Cell, 15, 986–998.

26. Mitteldorf, J. (2013) Telomere biology: cancer firewall or aging clock? Biochemistry (Moscow), 78, 1054–1060.

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

28. Libertini, G. (2009) The role of telomere-telomerase system in age-related fitness decline, a nameable process, in Telomeres: Function, Shortening and Lengthening (Mancini, L., ed.), Nova Science Publ. Inc., New York, pp. 77–132.

29. Libertini, G. (2014) The programmed aging paradigm: how we get old, Biochemistry (Moscow), 79, 1004–1016.

30. Libertini, G., and Ferrara, N. (2016) Aging of perennial cells and organ parts according to the programmed aging paradigm, Age (Dordr.), 38, 1–13.

31. 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., eds), Nova Science Publishers Inc., New York, pp. 35–96.

32. Goldsmith, T.C. (2008) Aging, evolvability, and the individual benefit requirement; medical implications of aging theory controversies, J. Theor. Biol., 252, 764–768.

33. Olovnikov, A.M. (2015) Chronographic theory of development, aging, and origin of cancer: role of chronomeres and printomeres, Curr. Aging Sci., 8, 76–88.

34. Skulachev, M.V., and Skulachev, V.P. (2014) New data on programmed aging – slow phenoptosis, Biochemistry (Moscow), 79, 977–993.

35. Moyzis, R.K., Buckingham, J.M., Cram, L.S., Dani, M., Deaven, L.L., Jones, M.D., Meyne, J., Ratliff, R.L., and Wu, J.R. (1988) A highly conserved repetitive DNA sequence (TTAGGG)n, present at the telomeres of human chromosomes, Proc. Natl. Acad. Sci. USA, 85, 6622–6626.

36. Blackburn, E.H. (1991) Structure and function of telomeres, Nature, 350, 569–573.

37. Olovnikov, A.M. (1971) Principle of marginotomy in template synthesis of polynucleotides, Dokl. Biochem., 201, 394–397.

38. 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.

39. Greider, C.W., and Blackburn, E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts, Cell, 43, 405–413.

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

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

42. Hayflick, L. (1965) The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res., 37, 614–636.

43. Gottschling, D.E., Aparicio, O.M., Billington, B.L., and Zakian, V.A. (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription, Cell, 63, 751–762.

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

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

46. Klapper, W., Heidorn, K., Kühne, K., Parwaresch, R., and Krupp, G. (1998) Telomerase activity in «immortal» fish, FEBS Lett., 434, 409–412.

47. Bodnar, A.G., Ouellette, M., Frolkis, M., Holt, S.E., Chiu, C., Morin, G.B., Harley, C.B., Shay, J.W., Lichtsteiner, S., and Wright, W.E. (1998) Extension of life-span by introduction of telomerase into normal human cells, Science, 279, 349–352.

48. Van Deursen, J.M. (2014) The role of senescent cells in ageing, Nature, 509, 439–446.

49. Beauséjour, C.M., Krtolica, A., Galimi, F., Narita, M., Lowe, S.W., Yaswen, P., and Campisi, J. (2003) Reversal of human cellular senescence: roles of the p53 and p16 pathways, EMBO J., 22, 4212–4222.

50. Libertini, G. (2013) Evidence for aging theories from the study of a hunter–gatherer people (ache of paraguay), Biochemistry (Moscow), 78, 1023–1032.

51. Rando, T.A., and Wyss-Coray, T. (2014) Stem cells as vehicles for youthful regeneration of aged tissues, J. Gerontol. A Biol. Sci. Med. Sci., 69, 39–42.

52. Mistriotis, P., and Andreadis, S.T. (2017) Vascular aging: molecular mechanisms and potential treatments for vascular rejuvenation, Ageing Res. Rev., 37, 94–116.

53. Libertini, G., and Ferrara, N. (2016) Possible interventions to modify aging, Biochemistry (Moscow), 81, 1413–1428.

54. Hill, J.M., Zalos, G., Halcox, J.P., 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.

55. Wilson, P.W., Castelli, W.P., and Kannel, W.B. (1987) Coronary risk prediction in adults (the framingham heart study), Am. J. Cardiol., 59, 91–94.

56. Webster, C., and Blau, H.M. (1990) Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: implications for cell and gene therapy, Somat. Cell Mol. Genet., 16, 557–565.

57. Seale, P., Asakura, A., and Rudnicki, M.A. (2001) The potential of muscle stem cells, Dev. Cell, 1, 333–342.

58. Tyner, S.D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., Park, S.H., Thompson, T., Karsenty, G., Bradley, A., and Donehower, L.A. (2002) p53 mutant mice that display early ageing-associated phenotypes, Nature, 415, 45–53.

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

60. Su, J.B. (2015) Vascular endothelial dysfunction and pharmacological treatment, World J. Cardiol., 7, 719–741.

61. Walter, D.H., Rittig, K., Bahlmann, F.H., Kirchmair, R., Silver, M., Murayama, T., Nishimura, H., Losordo, D.W., Asahara, T., and Isner, J.M. (2002) Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells, Circulation, 105, 3017–3024.

62. Quik, M., Huang, L.Z., Parameswaran, N., Bordia, T., Campos, C., and Perez, X.A. (2009) Multiple roles for nicotine in Parkinson’s disease, Biochem. Pharmacol., 78, 677–685.

63. Feingold, K.R., and Grunfeld, C. (2016) Cholesterol lowering drugs. In: De Groot, L. J., et al. (eds), Source Endotext, 2016 (www.endotext.org).

64. Cai, R., Yuan, Y., Sun, J., Xia, W., Huang, R., Tian, S., Dong, X., Shen, Y., and Wang, S. (2016) Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: a meta-analysis, Expert Opin. Pharmacother., 17, 1839–1849.

65. Liao, J.K., and Laufs, U. (2005) Pleiotropic effects of statins, Annu. Rev. Pharmacol. Toxicol., 45, 89–118.

66. Li, W., Du, D.Y., Liu, Y., Jiang, F., Zhang, P., and Li, Y.T. (2017) Long-term nicotine exposure induces dysfunction of mouse endothelial progenitor cells, Exp. Ther. Med., 13, 85–90.

67. Forero, D.A., González-Giraldo, Y., López-Quintero, C., Castro-Vega, L.J., Barreto, G.E., and Perry, G. (2016) Meta-analysis of telomere length in Alzheimer’s disease, J. Gerontol. A Biol. Sci. Med. Sci., 71, 1069–1073.

68. Falah, M., Najafi, M., Houshmand, M., and Farhadi, M. (2016) Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment, Clin. Interv. Aging, 11, 1003–1008.

69. Birch, J., Anderson, R.K., Correia-Melo, C., Jurk, D., Hewitt, G., Marques, F.M., Green, N.J., Moisey, E., Birrell, M.A., Belvisi, M.G., Black, F., Taylor, J.J., Fisher, A.J., De Soyza, A., and Passos, J.F. (2015) DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease, Am. J. Physiol. Lung Cell. Mol. Physiol., 309, 1124–1137.

70. Jonassaint, N.L., Guo, N., Califano, J.A., Montgomery, E.A., and Armanios, M. (2013) The gastrointestinal manifestations of telomere-mediated disease, Aging Cell, 12, 319–323.

71. Ueha, R., Ueha, S., Kondo, K., Sakamoto, T., Kikuta, S., Kanaya, K., Nishijima, H., Matsushima, K., and Yamasoba, T. (2016) Damage to olfactory progenitor cells is involved in cigarette smoke-induced olfactory dysfunction in mice, Am. J. Pathol., 186, 579–586.

72. Das, U.N. (2016) Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions, Arch. Med. Sci., 12, 1142–1157.

73. Vicente Miranda, H., El-Agnaf, O.M., and Outeiro, T.F. (2016) Glycation in Parkinson’s disease and Alzheimer’s disease, Mov. Disord., 31, 782–790.

74. Spielman, L.J., Little, J.P., and Klegeris, A. (2014) Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration, J. Neuroimmunol., 273, 8–21.

75. Han, C., Linser, P., Park, H.J., Kim, M.J., White, K., Vann, J.M., Ding, D., Prolla, T.A., and Someya, S. (2016) Sirt1 deficiency protects cochlear cells and delays the early onset of age-related hearing loss in C57BL/6 mice, Neurobiol. Aging, 43, 58–71.

76. Yun, J.H., Morrow, J., Owen, C.A., Qiu, W., Glass, K., Lao, T., Jiang, Z., Perrella, M.A., Silverman, E.K., Zhou, X., and Hersh, C.P. (2017) Transcriptomic analysis of lung tissue from cigarette smoke induced emphysema murine models and human COPD show shared and distinct pathways, Am. J. Respir. Cell. Mol. Biol., 57, 47–58.

77. Sung, I.Y., Park, B.C., Hah, Y.S., Cho, H.Y., Yun, J.W., Park, B.W., Kang, Y.H., Kim, H.C., Hwang, S.C., Rho, G.J., Kim, U.K., Woo, D.K., Oh, S.H., and Byun, J.H. (2015) FOXO1 is involved in the effects of cigarette smoke extract on osteoblastic differentiation of cultured human periosteum-derived cells, Int. J. Med. Sci., 12, 881–890.

78. Carmeli, E., and Reznick, A.Z. (1994) The physiology and biochemistry of skeletal muscle atrophy as a function of age, Proc. Soc. Exp. Biol. Med., 206, 103–113.

79. Zeng, H., Vaka, V.R., He, X., Booz, G.W., and Chen, J.X. (2015) High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss, J. Cell. Mol. Med., 19, 1847–1856.

80. Scheen, A.J. (2005) Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion? Diabetes Metab., 31, 5S27–5S34.

81. Yayama, K., Miyagi, R., Sugiyama, K., Sugaya, T., Fukamizu, A., and Okamoto, H. (2008) Angiotensin II regulates liver regeneration via type 1 receptor following partial hepatectomy in mice, Biol. Pharm. Bull., 31, 1356–1361.