Skip to main content
SpringerLink
Log in

Can Aging Be Programmed?

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Aging diminishes individual fitness, and aging could never evolve as an adaptive program according to the most prevalent model of evolutionary theory. On the other hand, some mechanisms of aging have been found to be conserved since the Cambrian explosion, and the physiology of aging sometimes looks like programmed self–destruction. Biostatisticians find evidence of an epigenetic aging clock, extending the clock that controls the growth and development into a realm of inexorably increasing mortality. These and other observations have suggested to some biologists that our understanding of aging is being constrained by restrictive evolutionary paradigms. Several computational models have been proposed; but evolution of an aging program requires group selection on a scale that goes beyond the theory of multilevel selection, a perspective that is already controversial. So, the question whether plausible models exist that can account for aging as a group–selected adaptation is central to our understanding of what aging is, where it comes from and, importantly, how anti–aging medicine might most propitiously be pursued. In a 2016 Aging Cell article, Kowald and Kirkwood reviewed computational models that evolve aging as an adaptation. They find fault with each of these models in turn, based on theory alone, and on this basis, they endorse the standing convention that aging must be understood in terms of trade–off models. But consideration of the corpus of experimental evidence creates a picture that stands in counterpoint to the conclusions of that review. Presented herein is a broad summary of that evidence, together with a description of one model that Kowald and Kirkwood omitted, the demographic theory of aging, which may be the most conservative, and therefore most plausible of the alternative evolutionary theories, and which is the subject of a book by the present author, published contemporaneously with Kowald and Kirkwood.

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.

Similar content being viewed by others

References

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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  CAS  PubMed  Google Scholar 

  3. Bredesen, D. E. (2004) The non–existent aging program: how does it work? Aging Cell, 3, 255–259.

    Article  CAS  PubMed  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. Goldsmith, T. (2003) The Evolution of Aging, Azinet Press.

    Google Scholar 

  6. Fabrizio, P., Battistella, L., Vardavas, R., Gattazzo, C., Lion, L. L., Diaspro, A., Dossen, J. W., Gralla, E. B., and Longo, V. D. (2004) Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae, J. Cell Biol., 166, 1055–1067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dytham, C., and Travis, J. M. (2006) Evolving dispersal and age at death, Oikos, 113, 530–538.

    Article  Google Scholar 

  8. Fahy, G. (2010) Precedents for the biological control of aging: postponement, prevention and reversal of aging processes, in Approaches to the Control of Aging: Building a Pathway to Human Life Extension (Fahy, G. M., ed.) Springer, New York.

    Google Scholar 

  9. Bowles, J. T. (1998) The evolution of aging: a new approach to an old problem of biology, Med. Hypotheses, 51, 179–221.

    Article  CAS  PubMed  Google Scholar 

  10. Dilman, V. M., and Dean, W. (1992) The Neuroendocrine Theory of Aging and Degenerative Disease, Center for BioGerontology, Pensacola, Florida.

    Google Scholar 

  11. Bernardes de Jesus, B., and Blasco, M. A. (2012) Potential of telomerase activation in extending health span and longevity, Curr. Opin. Cell Biol., 24, 739–743.

    Article  CAS  PubMed  Google Scholar 

  12. Andrews, W. H., Briggs, L., Brown, L. K., Foster, C. A., and Piatyszek, M. A. (2007) Assays for TERT Promoter Modulatory Agents Using Telomerase Structural RNA Component, US Grant US7226744B2, U. P. Office, USA.

    Google Scholar 

  13. Fossel, M. (1997) Reversing Human Aging, HarperCollins Publishers, New York.

    Google Scholar 

  14. Fossel, M. (2015) The Telomerase Revolution: the Enzyme that Holds the Key to Human Aging…and Will Soon Lead to Longer, Healthier Lives, Ben Bella Books, New York.

    Google Scholar 

  15. Barja, G. (2004) Free radicals and aging, Trends Neurosci., 27, 595–600.

    Article  CAS  PubMed  Google Scholar 

  16. Martinez–Cisuelo, V., Gomez, J., Garcia–Junceda, I., Naudi, A., Cabre, R., Mota–Martorell, N., Lopez–Torres, M., Gonzalez–Sanchez, M., Pamplona, R., and Barja, G. (2016) Rapamycin reverses age–related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle–aged mice, Exp. Gerontol., 83, 130–138.

    PubMed  Google Scholar 

  17. Pepper, J. W., and Smuts, B. B. (2002) A mechanism for the evolution of altruism among nonkin: positive assortment through environmental feedback, Am. Nat., 160, 205–213.

    Article  PubMed  Google Scholar 

  18. Stevens, L. (1989) The genetics and evolution of cannibalism in flour beetles (genus Tribolium), Evolution, 43, 169–179.

    PubMed  Google Scholar 

  19. Partridge, L., and Gems, D. (2002) Mechanisms of ageing: public or private? Nature Rev. Genet., 3, 165–175.

    Article  CAS  PubMed  Google Scholar 

  20. Guarente, L., and Kenyon, C. (2000) Genetic pathways that regulate ageing in model organisms, Nature, 408, 255–262.

    Article  CAS  PubMed  Google Scholar 

  21. Kenyon, C. (2001) A conserved regulatory system for aging, Cell, 105, 165–168.

    Article  CAS  PubMed  Google Scholar 

  22. Werfel, J., Ingber, D. E., and Bar–Yam, Y. (2015) Programed death is favored by natural selection in spatial systems, Phys. Rev. Lett., 114, 238103.

    Article  CAS  PubMed  Google Scholar 

  23. Mitteldorf, J. (2004) Aging selected for its own sake, Evol. Ecol. Res., 6, 1–17.

    Google Scholar 

  24. De Cabo, R., Carmona–Gutierres, D., Bernier, M., Yall, M. N., and Madeo, F. (2014) The search for antiaging interventions: from elixirs to fasting regimens, Cell, 157, 1515–1526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Katcher, H. (2013) Studies that shed new light on aging, Biochemistry (Moscow), 78, 1061–1070.

    Article  CAS  Google Scholar 

  26. Horvath, S. (2013) DNA methylation age of human tissues and cell types, Genome Biol., 14, R115.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Horvath, S., and Raj, K. J. (2018) DNA methylation–based biomarkers and the epigenetic clock theory of ageing, Nat. Rev. Genet., 19, 371–384.

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  29. De Magalhaes, J. P., Curado, J., and Church, G. M. (2009) Meta–analysis of age–related gene expression profiles identifies common signatures of aging, Bioinformatics, 25, 875–881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mitteldorf, J. (2016) Aging is a Group–Selected Adaptation: Theory, Evidence, and Medical Implications, CRC Press.

    Book  Google Scholar 

  31. Clark, W. R. (2004) Reflections on an unsolved problem of biology: the evolution of senescence and death, Adv. Gerontol., 14, 7–20.

    CAS  PubMed  Google Scholar 

  32. Williams, G. (1957) Pleiotropy, natural selection, and the evolution of senescence, Evolution, 11, 398–411.

    Google Scholar 

  33. Mitteldorf, J. (2006) Chaotic population dynamics and the evolution of aging: proposing a demographic theory of senescence, Evol. Ecol. Res., 8, 561–574.

    Google Scholar 

  34. Mitteldorf, J., and Goodnight, C. (2012) Post–reproductive life span and demographic stability, Oikos, 121, 1370–1378.

    Article  Google Scholar 

  35. Masoro, E. J., and Austad, S. N. (1996) The evolution of the antiaging action of dietary restriction: a hypothesis, J. Gerontol. Ser. A Biol. Sci. Med. Sci., 51, 387–391.

    Article  Google Scholar 

  36. Masoro, E. J. (2007) The role of hormesis in life extension by dietary restriction, Interdiscip. Top. Gerontol., 35, 1–17.

    CAS  PubMed  Google Scholar 

  37. Clark, W. R. (1998) Sex and the Origins of Death, Oxford University Press, USA.

    Google Scholar 

  38. Clark, W. R. (1999) A Means to an End: the Biological Basis of Aging and Death, Oxford University Press, Oxford–New York.

    Google Scholar 

  39. Cawthon, R. M., Smithn, K. R., O’Brien, E., Sivatchenko, A., and Kerber, R. A. (2003) Association between telomere length in blood and mortality in people aged 60 years or older, Lancet, 361, 393–395.

    Article  CAS  PubMed  Google Scholar 

  40. Rode, L., Nordestgaard, B. G., and Bojesen, S. E. (2015) Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population, J. Nat. Cancer Inst., 107, djv074.

    Article  CAS  PubMed  Google Scholar 

  41. Gordeeva, A. V., Labas, Y. A., and Zvyagilskaya, R. A. (2004) Apoptosis in unicellular organisms: mechanisms and evolution, Biochemistry (Moscow), 69, 1055–1066.

    Article  CAS  Google Scholar 

  42. Deponte, M. J. B. (2008) Programmed cell death in protists, Biochim. Biophys. Acta, 1783, 1396–1405.

    Article  CAS  PubMed  Google Scholar 

  43. Su, J. H., Anderson, A. J., and Cummings, B. J. (1994) Immunohistochemical evidence for apoptosis in Alzheimer’s disease, Neuroreport, 5, 2529–2533.

    Article  CAS  PubMed  Google Scholar 

  44. D’Amelio, M., Cavallucci, V., Middei, S., Marchetti, C., Pacioni, S., Ferri, A., Diamantini, A., De Zio, D., Carrara, P., Battistini, L., Moreno, S., Bacci, A., Ammassari–Teule, M., Marie, H., and Cecconi, F. (2011) Caspase–3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease, Nat. Neurosci., 14, 69–76.

    Article  CAS  PubMed  Google Scholar 

  45. Behl, C. (2000) Apoptosis and Alzheimer’s disease, J. Neur. Trans., 107, 1325–1344.

    Article  CAS  Google Scholar 

  46. Marzetti, E., and Leeuwenburgh, C. (2006) Skeletal muscle apoptosis, sarcopenia and frailty at old age, Exp. Gerontol., 41, 1234–1238.

    CAS  Google Scholar 

  47. Pistilli, E. E., Jackson, J. R., and Alway, S. E. (2006) Death receptor–associated pro–apoptotic signaling in aged skeletal muscle, Apoptosis, 11, 2115–2126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shen, J., and Tower, J. (2009) Programmed cell death and apoptosis in aging and life span regulation, Discov. Med., 8, 223–226.

    PubMed  Google Scholar 

  49. Chaloupka, J., and Vinter, V. J. F. (1996) Programmed cell death in bacteria, Folia Microbiol., 41, 451–464.

    Article  CAS  Google Scholar 

  50. Neafsey, P. J. (1990) Longevity hormesis. A review, Mech. Ageing Dev., 51, 1–31.

    Article  CAS  PubMed  Google Scholar 

  51. Luckey, T. D. (1991) Radiation Hormesis, CRC Press.

    Google Scholar 

  52. Calabrese, E. J. (2005) Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology, Toxicol. Appl. Pharmacol., 204, 1–8.

    Article  CAS  PubMed  Google Scholar 

  53. Forbes, V. (2000) Is hormesis an evolutionary expectation? Funct. Ecol., 4, 12–24.

    Article  Google Scholar 

  54. Blagosklonny, M. V. (2011) Hormesis does not make sense except in the light of TOR–driven aging, Aging (Albany N. Y.), 3, 1051–1062.

    CAS  Google Scholar 

  55. Olsen, A., Vantipalli, M. C., and Lithgow, G. J. (2006) Lifespan extension of Caenorhabditis elegans following repeated mild hormetic heat treatments, Biogerontology, 7, 221–230.

    Article  PubMed  Google Scholar 

  56. Holloszy, J. O., and Smith, E. K. (1986) Longevity of cold-exposed rats: a reevaluation of the “rate–of–living theory”, J. Appl. Physiol., 61, 1656–1660.

    Article  CAS  PubMed  Google Scholar 

  57. Heywood, R., Sortwell, R. J., Noel, P. R., Street, A. E., Prentice, D. E., Roe, F. J., Wadsworth, P. F., Worden, A. N., and Van Abbe, N. J. (1979) Safety evaluation of tooth–paste containing chloroform. III. Long–term study in beagle dogs, J. Environ. Pathol. Toxicol., 2, 835–851.

    CAS  PubMed  Google Scholar 

  58. Hekimi, S., Lapointe, J., and Wen, Y. (2011) Taking a “good” look at free radicals in the aging process, Trends Cell Biol., 21, 569–576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ristow, M., and Schmeisser, S. (2011) Extending life span by increasing oxidative stress, Free Radic. Biol. Med., 51, 327–336.

    Article  CAS  PubMed  Google Scholar 

  60. Caratero, A., Courtade, M., Bonnet, L., Planel, H., and Caratero, C. (1997) Effect of a continuous gamma irradiation at a very low dose on the life span of mice, Gerontology, 44, 272–276.

    Article  Google Scholar 

  61. Phelan, J., and Austad, S. (1988) Natural selection, dietary restriction, and extended longevity, Growth Dev. Aging, 53, 4–6.

    Google Scholar 

  62. Harrison, D. E., and Archer, J. R. (1989) Natural selection for extended longevity from food restriction, Growth Dev. Aging, 53,3.

    CAS  PubMed  Google Scholar 

  63. Kirkwood, T. (1977) Evolution of aging, Nature, 270, 301–304.

    Article  CAS  PubMed  Google Scholar 

  64. Shanley, D. P., and Kirkwood, T. B. (2000) Calorie restriction and aging: a life–history analysis, Evol. Int. J. Org. Evol., 54, 740–750.

    Article  CAS  Google Scholar 

  65. Reimers, C. D., Knapp, G., and Reimers, A. K. (2012) Does physical activity increase life expectancy? A review of the literature, J. Aging Res., 2012, Article ID 243958.

  66. Holloszy, J. O. (1993) Exercise increases average longevity of female rats despite increased food intake and no growth retardation, J. Gerontol., 48, 97–100.

    Article  Google Scholar 

  67. Bronikowski, A. M., Carter, P. A., Morgan, T. J., Garland, T., Jr., Ung, N., Pugh, T. D., Weindruch, R., and Prolla, T. A. (2003) Lifelong voluntary exercise in the mouse prevents age–related alterations in gene expression in the heart, Physiol. Genomics, 12, 129–138.

    Article  CAS  PubMed  Google Scholar 

  68. Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., and Bluher, M. (2009) Antioxidants prevent health–promoting effects of physical exercise in humans, Proc. Natl. Acad. Sci. USA, 106, 8665–8670.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Johnson, T. E. (1990) Increased life–span of age–1 mutants in Caenorhabditis elegans and lower gompertz rate of aging, Science, 249, 908–912.

    Article  CAS  PubMed  Google Scholar 

  70. Johnson, T. E., Tedesco, P. M., and Lithgow, G. J. (1993) Comparing mutants, selective breeding, and transgenics in the dissection of aging processes of Caenorhabditis elegans, Genetica, 91, 65–77.

    CAS  PubMed  Google Scholar 

  71. Kenyon, C. (2005) The plasticity of aging: insights from long–lived mutants, Cell, 120, 449–460.

    Article  CAS  PubMed  Google Scholar 

  72. Jenkins, N. L., McColl, G., and Lithgow, G. J. (2004) Fitness cost of extended lifespan in Caenorhabditis elegans, Proc. Biol. Sci., 271, 2523–2526.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Mattison, J., Wright, C., Bronson, R. T., Roth, G. S., Ingram, D. K., and Bartke, A. (2000) Studies of aging in ames dwarf mice: effects of caloric restriction, J. Am. Aging Assoc., 23, 9–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Bartke, A., Wright, J. C., Mabtison, J. A., Ingram, D. K., Miller, R. A., and Roth, G. S. (2001) Longevity: extending the lifespan of long–lived mice, Nature, 414,412.

    Article  CAS  PubMed  Google Scholar 

  75. Rogina, B., Helfand, S., and Frankel, S. L. (2002) Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction, Science, 298, 1745.

    Article  CAS  PubMed  Google Scholar 

  76. Tissenbaum, H. A., and Guarente, L. J. N. (2001) Increased dosage of a sir–2 gene extends lifespan in Caenorhabditis elegans, Nature, 410, 227–230.

    Article  CAS  PubMed  Google Scholar 

  77. Van Raamsdonk, J. M., and Hekimi, S. (2009) Deletion of the mitochondrial superoxide dismutase sod–2 extends lifespan in Caenorhabditis elegans, PLoS Genet., 5, e1000361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Arantes–Oliveira, N., Berman, J. R., and Kenyon, M. C. (2003) Healthy animals with extreme longevity, Science, 302,611.

    Article  PubMed  Google Scholar 

  79. Trubitsyn, A. (2006) Evolutionary mechanisms of species–specific lifespan, Adv. Gerontol., 19, 13–24.

    CAS  PubMed  Google Scholar 

  80. Gilpin, M. E. (1975) Group Selection in Predator–Prey Communities, Monographs in Population Biology, Vol. 9, Princeton University Press, Princeton.

    Google Scholar 

  81. Jones, O. R., Scheuerlein, A., Salguero–Gomez, R., and Camarda, C. G. (2014) Diversity of ageing across the tree of life, Nature, 505, 169–173.

    Article  CAS  PubMed  Google Scholar 

  82. Harper, J. L. (2010) Population Biology of Plants, Blackburn Press.

    Google Scholar 

  83. Slobodkin, L. B. (1968) How to be a predator, Am. Zool., 8, 43–51.

    Article  Google Scholar 

  84. Benton, T., and Grant, A. (2000) Evolutionary fitness in ecology: comparing measures of fitness in stochastic, density–dependent environments, Evol. Ecol. Res., 2, 769–789.

    Google Scholar 

  85. Mitteldorf, J., and Pepper, J. (2009) Senescence as an adaptation to limit the spread of disease, J. Theor. Biol., 260, 186–195.

    Article  PubMed  Google Scholar 

  86. Socolar, J., Richards, S., and Wilson, W. G. (2001) Evolution in a spatially structured population subject to rare epidemics, Phys. Rev., 63, 1–8.

    Google Scholar 

  87. Bryant, M. J., and Reznick, D. (2004) Comparative studies of senescence in natural populations of guppies, Am. Nat., 163, 55–68.

    Article  PubMed  Google Scholar 

  88. Reznick, D., Nunney, L., and Tessier, A. (2000) Big houses, big cars, superfleas and the costs of reproduction, Trends Ecol. Evol., 15, 421–425.

    Article  CAS  Google Scholar 

  89. Spitze, K. (1991) Chaoborus predation and life history evolution in Daphnia pulex: temporal pattern of population diversity, fitness, and mean life history, Evolution, 45, 82–92.

    Google Scholar 

  90. Mitteldorf, J. (2012) Adaptive aging in the context of evolutionary theory, Biochemistry (Moscow), 77, 716–725.

    Article  CAS  Google Scholar 

  91. Mitteldorf, J., and Pepper, J. (2007) How can evolutionary theory accommodate recent empirical results on organismal senescence? Theory Biosci., 126, 3–8.

    Article  PubMed  Google Scholar 

  92. Goranson, N., Ebersole, J., and Brault, S. (2005) Resolving an adaptive conundrum: reproduction in Caenorhabditis elegans is not sperm–limited when food is scarce, Evol. Ecol. Res., 7, 325–333.

    Google Scholar 

  93. Lack, D. J. (1947) The significance of clutch size, Ibis, 89, 302–352.

    Article  Google Scholar 

  94. Ydenberg, R., and Bertram, D. (1989) Lack’s clutch size hypothesis and brood enlargement studies on colonial seabirds, Colonial Waterbirds, 12, 134–137.

    Article  Google Scholar 

  95. Charlesworth, B. (1980) The cost of sex in relation to mating system, J. Theor. Biol., 84, 655–671.

    Article  CAS  PubMed  Google Scholar 

  96. Williams, G. (1975) Sex and Evolution, Princeton University Press, Princeton, NJ.

    Google Scholar 

  97. Bell, G. (1982) The Masterpiece of Nature: the Evolution and Genetics of Sexuality, University of California Press, Berkeley.

    Google Scholar 

  98. Maynard Smith, J. (1978) The Evolution of Sex, Cambridge University Press, Cambridge, UK.

    Google Scholar 

  99. Ridley, M. (1993) The Red Queen, Penguin, London.

    Google Scholar 

  100. Villeda, S. A., Plambeck, K. E., Middeldorp, J., Castellano, J. M., Mosher, K. I., Luo, J., Smith, L. K., Bieri, G., Lin, K., Berdnik, D., Wabl, R., Udeochu, J., Wheatley, E. D., Zou, B., Simmons, D. A., Xie, X. S., Longo, F. M., and Wyss–Coray, T. (2014) Young blood reverses age–related impairments in cognitive function and synaptic plasticity in mice, Nat. Med., 20, 659–663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Conboy, I., Wagers, A. J., Girma, E. R., Irving, L., Weissman, I. L., and Thomas, A. (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment, Nature, 433, 760–764.

    Article  CAS  PubMed  Google Scholar 

  102. Elabd, C., Cosin, W., Upadhyayula, P., Chen, R. Y., Chooljian, M. S., Li, J., Kung, S., Jiang, K. P., and Couboy, I. M. (2014) Oxytocin is an age–specific circulating hormone that is necessary for muscle maintenance and regeneration, Nat. Comm., 5, 1–11.

    Article  CAS  Google Scholar 

  103. Ruckh, J. M., Zhao, J. W., Shadrach, J. L., van Wijngaarden, P., Rao, T. N., Wagers, T. N., and Franklin, R. J. (2012) Rejuvenation of regeneration in the aging central nervous system, Cell Stem Cell, 10, 96–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., Li, B., Liu, G., and Cai, D. (2013) Hypothalamic programming of systemic ageing involving IKK–[bgr], NF–[kgr]B and GnRH, Nature, 497, 211–216.

    CAS  Google Scholar 

  105. Carlson, M. E., Conboy, M. J., Hsu, M., Barchas, L., Jeong, J., Agrawal, A., Mikels, A. J., Agrawal, S., Schaffer, D. V., and Conboy, I. M. (2009) Relative roles of TGF–β1 and Wnt in the systemic regulation and aging of satellite cell responses, Aging Cell, 8, 676–689.

    Article  CAS  PubMed  Google Scholar 

  106. Merry, B. J., and Holehan, A. M. (1981) Serum profiles of LH, FSH, testosterone and 5 alpha–DHT from 21 to 1000 days of age in ad libitum fed and dietary restricted rats, Exp. Gerontol., 16, 431–444.

    CAS  Google Scholar 

  107. Peltoketo, H., Strauss, L., Karjalainen, R., Zhang, M., Stamp, G., Segaloff, D., Poutanen, M., and Huhtaniemi, I. (2010) Female mice expressing constitutively active FSH receptor present with a phenotype of premature follicle depletion, premature aging and teratomas, Endocr. Abs., 21,326.

    Google Scholar 

  108. Burger, H. G., Dudley, E. C., Robertson, D. M., and Denntrstein, L. (2002) Hormonal changes in the menopause transition, Recent Prog. Horm. Res., 7, 257–276.

    Article  Google Scholar 

  109. Kulju, K. S., and Lehman, J. M. (1995) Increased p53 protein associated with aging in human diploid fibroblasts, Exp. Cell Res., 217, 336–345.

    Article  CAS  PubMed  Google Scholar 

  110. Donehower, L. (2002) Does p53 affect organismal aging? J. Cell. Physiol., 192, 23–33.

    Article  CAS  PubMed  Google Scholar 

  111. Dorszewska, J., and Adamczewska–Goncerzewicz, Z. (2004) Oxidative damage to DNA, p53 gene expression and p53 protein level in the process of aging in rat brain, Respir. Physiol. Neurobiol., 139, 227–236.

    CAS  Google Scholar 

  112. Anisimov, V. N., Popovich, I. G., Zabezhinski, M. A., Anisimov, S. V., Vesnushkin, G. M., and Vinogradova, I. A. (2006) Melatonin as antioxidant, geroprotector and anticarcinogen, Biochim. Biophys. Acta, 1757, 573–589.

    Article  CAS  PubMed  Google Scholar 

  113. Sharman, E. H., Bondy, S. C., Sharman, K. G., Lahiri, D., Cotman, C. W., and Perreau, V. M. (2007) Effects of melatonin and age on gene expression in mouse CNS using microarray analysis, Neurochem. Int., 50, 336–344.

    Article  CAS  PubMed  Google Scholar 

  114. Aveleira, C. A., Botelho, M., and Cavadas, C. (2015) NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging? Autophagy, 11, 1431–1433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Medawar, P. B. (1952) An Unsolved Problem of Biology, Published for the college by H. K. Lewis, London.

    Google Scholar 

  116. Edney, E. B., and Gill, R. W. (1968) Evolution of senescence and specific longevity, Nature, 220, 281–282.

    Article  CAS  PubMed  Google Scholar 

  117. Bonduriansky, R., and Brassil, C. E. (2002) Senescence: rapid and costly ageing in wild male flies, Nature, 420,377.

    Article  CAS  PubMed  Google Scholar 

  118. Promislow, D. E. (1991) Senescence in natural populations of mammals: a comparative study, Evolution, 45, 1869–1887.

    Article  PubMed  Google Scholar 

  119. Ricklefs, R. (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.

    CAS  PubMed  Google Scholar 

  120. Nussey, D. H., Froy, H., Lemaitre, J. F., Gaillard, J. M., and Austad, S. N. (2012) Senescence in natural populations of animals: widespread evidence and its implications for bio–gerontology, Ageing Res. Rev., 12, 214–225.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute of Biological Sciences, 102206, Beijing, China

    J. Mitteldorf

Authors
  1. J. Mitteldorf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Mitteldorf.

Additional information

Published in Russian in Biokhimiya, 2018, Vol. 83, No. 12, pp. 1870–1883.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mitteldorf, J. Can Aging Be Programmed?. Biochemistry Moscow 83, 1524–1533 (2018). https://doi.org/10.1134/S0006297918120106

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297918120106

Keywords

Search

Navigation