Mechanisms of aging: public or private?

Ageing — the decline in survival and fecundity with advancing age — is caused by damage to macromolecules and tissues. Ageing is not a programmed process, in the sense that no genes are known to have evolved specifically to cause damage and ageing. Mechanisms of ageing might therefore not be expected to be as highly conserved between distantly related organisms as are mechanisms of development and metabolism. However, evidence is mounting that modulators of the rate of ageing are conserved over large evolutionary distances. As we discuss in this review, this conservation might stem from mechanisms that match reproductive rate to nutrient supply.

[1]  S. Hekimi The Molecular Genetics of Aging , 2000, Results and Problems in Cell Differentiation.

[2]  Mark D. Johnson,et al.  Early neonatal death in mice homozygous for a null allele of the insulin receptor gene , 1996, Nature Genetics.

[3]  M. Klass,et al.  Non-ageing developmental variant of Caenorhabditis elegans , 1976, Nature.

[4]  C. Kosack,et al.  LABORATORY , 1949, American journal of public health and the nation's health.

[5]  Chance, Development, and Aging by Caleb E. Finch and T.B.L. Kirkwood, Oxford University Press, New York, USA , 2000, Biogerontology.

[6]  Yau-Huei Wei,et al.  Oxidative Damage and Mutation to Mitochondrial DNA and Age‐dependent Decline of Mitochondrial Respiratory Function a , 1998, Annals of the New York Academy of Sciences.

[7]  D L Riddle,et al.  daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. , 2000, Genes & development.

[8]  R. S. Sohal,et al.  Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse , 1994, Mechanisms of Ageing and Development.

[9]  S. Bennett,et al.  Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[10]  T. Work,et al.  Biogenesis of Mitochondria , 1966, Nature.

[11]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[12]  J. Kopchick,et al.  Is the Laron mouse an accurate model of Laron syndrome? , 1999, Molecular genetics and metabolism.

[13]  A. Leroi,et al.  Evolution of germ-line signals that regulate growth and aging in nematodes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  B. Lakowski,et al.  The genetics of caloric restriction in Caenorhabditis elegans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Wanke,et al.  Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: Lessons from transgenic animal models , 1993, Mechanisms of Ageing and Development.

[16]  A. Bartke Delayed aging in Ames dwarf mice. Relationships to endocrine function and body size. , 2000, Results and problems in cell differentiation.

[17]  Andrzej Bartke,et al.  Dwarf mice and the ageing process , 1996, Nature.

[18]  Eka Swadiansa The hypothesis , 1990 .

[19]  Douglas C. Wallace,et al.  Radicals r'aging , 1998, Nature Genetics.

[20]  D. Clemmons,et al.  Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. , 2000, Endocrinology.

[21]  A. Spradling,et al.  Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. , 2001, Developmental biology.

[22]  A. Leroi,et al.  Molecular signals versus the Loi de Balancement. , 2001, Trends in ecology & evolution.

[23]  B. Charlesworth,et al.  Unravelling the Evolutionary Advantage of Sex : a Commentary on ' Mutation–selection Balance and the Evolutionary Advantage of Sex and Recombination ' , 2022 .

[24]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[25]  K. Hughes,et al.  A test of evolutionary theories of aging , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Simon A. Levin,et al.  Ecology: Achievement and Challenge , 2001 .

[27]  M R Rose,et al.  Evolution of senescence: late survival sacrificed for reproduction. , 1991, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[28]  J. Haldane New paths in genetics , 1942 .

[29]  S. Austad,et al.  The evolution of the antiaging action of dietary restriction: a hypothesis. , 1996, The journals of gerontology. Series A, Biological sciences and medical sciences.

[30]  C. Kenyon A Conserved Regulatory System for Aging , 2001, Cell.

[31]  M. Klass,et al.  Aging in the nematode Caenorhabditis elegans: Major biological and environmental factors influencing life span , 1977, Mechanisms of Ageing and Development.

[32]  D. Ingram,et al.  Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta) , 2000, Mechanisms of Ageing and Development.

[33]  E. Hafen,et al.  An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control , 2001, Current Biology.

[34]  S. Leevers,et al.  The genetic control of organ growth: insights from Drosophila. , 2000, Current opinion in genetics & development.

[35]  T. Wagner,et al.  A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Pier Paolo Pandolfi,et al.  The p66shc adaptor protein controls oxidative stress response and life span in mammals , 1999, Nature.

[37]  L. Partridge,et al.  Optimally, mutation and the evolution of ageing , 1993, Nature.

[38]  L. Partridge,et al.  Insulin/IGF signalling and ageing: seeing the bigger picture. , 2001, Current opinion in genetics & development.

[39]  L. Partridge,et al.  EVOLUTIONARY EFFECTS OF SELECTION ON AGE AT REPRODUCTION IN LARVAL AND ADULT: DROSOPHILA MELANOGASTER , 1993, Evolution; international journal of organic evolution.

[40]  J. Apfeld,et al.  Cell Nonautonomy of C. elegans daf-2 Function in the Regulation of Diapause and Life Span , 1998, Cell.

[41]  J. M. Wattiaux,et al.  CUMULATIVE PARENTAL AGE EFFECTS IN DROSOPHILA SUBOBSCURA , 1968, Evolution; international journal of organic evolution.

[42]  T. Wagner,et al.  Fertility of transgenic female mice expressing bovine growth hormone or human growth hormone variant genes. , 1991, Biology of reproduction.

[43]  J. Curtsinger,et al.  Age-specific properties of spontaneous mutations affecting mortality in Drosophila melanogaster. , 1998, Genetics.

[44]  J. Apfeld,et al.  Regulation of Life-Span by Germ-Line Stem Cells in Caenorhabditis elegans , 2002, Science.

[45]  C. Geyer,et al.  Toward reconciling inferences concerning genetic variation in senescence in Drosophila melanogaster. , 1999, Genetics.

[46]  G. Ruvkun,et al.  The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans , 1997, Nature.

[47]  B. Merry,et al.  THE EXPERIMENTAL MANIPULATION OF AGEING BY DIET , 1986, Biological reviews of the Cambridge Philosophical Society.

[48]  J. Apfeld,et al.  Regulation of lifespan by sensory perception in Caenorhabditis elegans , 1999, Nature.

[49]  J. Campisi,et al.  Aging and Cancer: The Double‐Edged Sword of Replicative Senescence , 1997, Journal of the American Geriatrics Society.

[50]  Michael A. Costa,et al.  Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. , 2001, Genes & development.

[51]  L. Partridge,et al.  A delayed wave of death from reproduction in Drosophila. , 1999, Science.

[52]  B. Halliwell,et al.  Free radicals in biology and medicine , 1985 .

[53]  R. Miskin,et al.  Transgenic mice overexpressing urokinase-type plasminogen activator in the brain exhibit reduced food consumption, body weight and size, and increased longevity. , 1997, The journals of gerontology. Series A, Biological sciences and medical sciences.

[54]  M. Tatar,et al.  A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function , 2001, Science.

[55]  L. Keller,et al.  Extraordinary lifespans in ants: a test of evolutionary theories of ageing , 1997, Nature.

[56]  P. Medawar Old Age and Natural Death , 2019, The Uniqueness of the Individual.

[57]  R. Weindruch,et al.  Decreased mitochondrial RNA levels without accumulation of mitochondrial DNA deletions in aging Drosophila melanogaster. , 1998, Mutation research.

[58]  Cynthia Kenyon,et al.  Signals from the reproductive system regulate the lifespan of C. elegans , 1999, Nature.

[59]  D. Riddle,et al.  Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. , 1998, Genetics.

[60]  D. Hartl,et al.  Principles of population genetics , 1981 .

[61]  D. Riddle,et al.  Genes that regulate both development and longevity in Caenorhabditis elegans. , 1995, Genetics.

[62]  Brian Charlesworth,et al.  A genetic analysis of senescence in Drosophila , 1994, Nature.

[63]  K. Hughes,et al.  Age-specific inbreeding depression and components of genetic variance in relation to the evolution of senescence. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[64]  J. Vanfleteren,et al.  The gerontogenes age‐1 and daf‐2 determine metabolic rate potential in aging Caenorhabditis elegans , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[65]  L. Partridge,et al.  Another set of responses and correlated responses to selection on age at reproduction in Drosophila melanogaster , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[66]  Andrzej Bartke,et al.  Longevity: Extending the lifespan of long-lived mice , 2001, Nature.

[67]  L. Partridge,et al.  Female fitness in Drosophila melanogaster: an interaction between the effect of nutrition and of encounter rate with males , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[68]  Donald L. Lee The Biology of Nematodes , 2002 .

[69]  G. Bartosz Free Radicals in Biology and Medicine , 2000 .

[70]  D. Promislow,et al.  Age-specific patterns of genetic variance in Drosophila melanogaster. II. Fecundity and its genetic covariance with age-specific mortality. , 1996, Genetics.

[71]  Marco Festa-Bianchet,et al.  AGE‐SPECIFIC SURVIVAL IN FIVE POPULATIONS OF UNGULATES: EVIDENCE OF SENESCENCE , 1999 .

[72]  S. Austad,et al.  Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials. , 1991, Journal of gerontology.

[73]  M. Frasch,et al.  The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. , 1995, The EMBO journal.

[74]  George C. Williams,et al.  PLEIOTROPY, NATURAL SELECTION, AND THE EVOLUTION OF SENESCENCE , 1957, Science of Aging Knowledge Environment.

[75]  W. Hamilton The moulding of senescence by natural selection. , 1966, Journal of theoretical biology.

[76]  P. Dolman Ecology: achievement and challenge , 2002 .

[77]  B. Zwaan,et al.  DIRECT SELECTION ON LIFE SPAN IN DROSOPHILA MELANOGASTER , 1995, Evolution; international journal of organic evolution.

[78]  S. O’Rahilly,et al.  Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism , 1993, The Lancet.

[79]  E. W. Hutchinson Quantitative genetics of postponed senescence in Drosophila melanogaster. , 1990 .

[80]  L. Partridge,et al.  DIRECT AND CORRELATED RESPONSES TO SELECTION ON AGE AT REPRODUCTION IN DROSOPHILA MELANOGASTER , 1992, Evolution; international journal of organic evolution.

[81]  R. Weindruch,et al.  Effects of caloric restriction on skeletal muscle mitochondrial proton leak in aging rats. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[82]  J. Curtsinger,et al.  The evolution of age-specific mortality rates in Drosophila melanogaster: genetic divergence among unselected lines. , 1999, Genetics.

[83]  G. Ruvkun,et al.  A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans , 1996, Nature.

[84]  R Holliday,et al.  Food, reproduction and longevity: is the extended lifespan of calorie-restricted animals an evolutionary adaptation? , 1989, BioEssays : news and reviews in molecular, cellular and developmental biology.

[85]  D L Riddle,et al.  Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans. , 2000, Genetics.

[86]  G. Lithgow,et al.  Natural selection: Evolution of lifespan in C. elegans , 2000, Nature.

[87]  P. Medawar UNSOLVED problem of biology. , 1953, The Medical journal of Australia.

[88]  B. Charlesworth,et al.  Ageing: Levelling of the grim reaper , 1997, Current Biology.

[89]  Michael R Rose,et al.  LABORATORY EVOLUTION OF POSTPONED SENESCENCE IN DROSOPHILA MELANOGASTER , 1984, Evolution; international journal of organic evolution.

[90]  J. Culotti,et al.  daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans. , 1998, Development.

[91]  R. Korona Genetic divergence and fitness convergence under uniform selection in experimental populations of bacteria. , 1996, Genetics.

[92]  M. Portero-Otín,et al.  Heart fatty acid unsaturation and lipid peroxidation, and aging rate, are lower in the canary and the parakeet than in the mouse , 1999, Aging.

[93]  T. Johnson,et al.  A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. , 2002, Genetics.

[94]  E. Hafen,et al.  Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein , 2001, Science.

[95]  B. Ames,et al.  The free radical theory of aging matures. , 1998, Physiological reviews.

[96]  Richard A. Miller,et al.  Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[97]  B. Charlesworth,et al.  Genetics of life history in Drosophila melanogaster. II. Exploratory selection experiments. , 1981, Genetics.

[98]  R. Raff,et al.  Evidence for a clade of nematodes, arthropods and other moulting animals , 1997, Nature.

[99]  G. S. Mani,et al.  Mutational order: a major stochastic process in evolution , 1990, Proceedings of the Royal Society of London. B. Biological Sciences.

[100]  D. Riddle,et al.  Longevity in Caenorhabditis elegans reduced by mating but not gamete production , 1996, Nature.

[101]  S. Austad,et al.  Genetic analysis of ageing: role of oxidative damage and environmental stresses , 1996, Nature Genetics.

[102]  L. Luckinbill,et al.  SELECTION FOR DELAYED SENESCENCE IN DROSOPHILA MELANOGASTER , 1984, Evolution; international journal of organic evolution.

[103]  P. Defossez,et al.  Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. , 2000, Science.

[104]  B. Charlesworth,et al.  Evolution in Age-Structured Populations. , 1995 .

[105]  V. Rottiers,et al.  A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. , 2001, Developmental cell.

[106]  D. Promislow,et al.  Age-specific patterns of genetic variance in Drosophila melanogaster. I. Mortality. , 1996, Genetics.

[107]  Koutarou D. Kimura,et al.  Regulation of C. elegans life-span by insulinlike signaling in the nervous system. , 2000, Science.

[108]  Caleb E. Finch,et al.  Longevity, senescence, and the genome , 1990 .

[109]  R. Ricklefs Evolutionary Theories of Aging: Confirmation of a Fundamental Prediction, with Implications for the Genetic Basis and Evolution of Life Span , 1998, The American Naturalist.