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2 - The biology of ageing

A primer

Published online by Cambridge University Press:  05 June 2012

João Pedro de Magalhães
Affiliation:
University of Liverpool
Ian Stuart-Hamilton
Affiliation:
University of Glamorgan
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Summary

OVERVIEW

This chapter introduces key biological concepts of ageing. First, it defines ageing and presents the main features of human ageing, followed by a consideration of evolutionary models of ageing. Causes of variation in ageing (genetic and dietary) are reviewed, before examining biological theories of the causes of ageing.

Introduction

Thanks to technological progress in different areas, including biomedical breakthroughs in preventing and treating infectious diseases, longevity has been increasing dramatically for decades. The life expectancy at birth in the UK for boys and girls rose, respectively, from 45 and 49 years in 1901 to 75 and 80 in 1999 with similar figures reported for other industrialized nations (see Chapter 1 for further discussion). A direct consequence is a steady increase in the proportion of people living to an age where their health and well-being are restricted by ageing. By the year 2050, it is estimated that the percentage of people in the UK over the age of 65 will rise to over 25 per cent, compared to 14 per cent in 2004 (Smith, 2004).

The greying of the population, discussed elsewhere (see Chapter 1), implies major medical and societal changes. Although ageing is no longer considered by health professionals as a direct cause of death (Hayflick, 1994), the major killers in industrialized nations are now age-related diseases like cancer, diseases of the heart and neurodegenerative diseases.

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Publisher: Cambridge University Press
Print publication year: 2011

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References

Arking, R. (2006) The biology of aging: observations and principles. Oxford University Press.Google Scholar
Artandi, S.E., Alson, S., Tietze, M.K.et al. (2002) Constitutive telomerase expression promotes mammary carcinomas in aging mice, Proceedings of the National Academy of Sciences of the USA, 99(12), 8191–6.CrossRefGoogle ScholarPubMed
Austad, S.N. (1997a) Comparative aging and life histories in mammals, Experimental Gerontology, 32(1–2), 23–38.CrossRefGoogle ScholarPubMed
Austad, S.N. (1997b) Why we age: what science is discovering about the body's journey through life. New York: John Wiley & Sons.Google Scholar
Austad, S.N. (2006) Why women live longer than men: sex differences in longevity, Gender Medicine, 3(2), 79–92.CrossRefGoogle ScholarPubMed
Bartke, A. (2003) Can growth hormone (GH) accelerate aging? Evidence from GH‐transgenic mice, Neuroendocrinology, 78(4), 210–16.CrossRefGoogle ScholarPubMed
Bartke, A., Coschigano, K., Kopchick, J.et al. (2001) Genes that prolong life: relationships of growth hormone and growth to aging and life span, Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 56(8), B340–9.CrossRefGoogle ScholarPubMed
Beckman, K.B. and Ames, B.N. (1998) The free radical theory of aging matures, Physiological Reviews, 78(2), 547–81.CrossRefGoogle ScholarPubMed
Brown-Borg, H.M., Borg, K.E., Meliska, C.J.et al. (1996) Dwarf mice and the ageing process, Nature, 384(6604), 33.CrossRefGoogle ScholarPubMed
Campisi, J. (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors, Cell, 120(4), 513–22.CrossRefGoogle ScholarPubMed
Colman, R.J., Anderson, R.M., Johnson, S.C.et al. (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys, Science, 325(5937), 201–4.CrossRefGoogle ScholarPubMed
Comfort, A. (1964) Ageing: the biology of senescence. London: Routledge & Kegan Paul.Google Scholar
Cooper, T.M., Mockett, R.J., Sohal, B.H.et al. (2004) Effect of caloric restriction on life span of the housefly, Musca domestica, FASEB Journal, 18(13), 1591–3.CrossRefGoogle ScholarPubMed
Cristofalo, V.J., Allen, R.G., Pignolo, R.J.et al. (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation, Proceedings of the National Academy of Sciences of the USA, 95(18), 10614–19.CrossRefGoogle Scholar
Magalhães, J.P. (2003) Is mammalian aging genetically controlled?, Biogerontology, 4(2), 119–20.CrossRefGoogle ScholarPubMed
Magalhães, J.P. (2004) From cells to ageing: a review of models and mechanisms of cellular senescence and their impact on human ageing, Experimental Cell Research, 300(1), 1–10.CrossRefGoogle ScholarPubMed
Magalhães, J.P. (2005) Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations, Ageing Research Reviews, 4(1), 1–22.Google ScholarPubMed
Magalhães, J.P. and Church, G.M. (2005) Genomes optimize reproduction: aging as a consequence of the developmental program, Physiology (Bethesda), 20, 252–9.Google ScholarPubMed
Magalhães, J.P., Costa, J. and Church, G.M. (2007) An analysis of the relationship between metabolism, developmental schedules, and longevity using phylogenetic independent contrasts, Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 62(2), 149–60.CrossRefGoogle ScholarPubMed
Magalhães, J.P., Finch, C.E. and Janssens, G. (2010) Next-generation sequencing in aging research: emerging applications, problems, pitfalls and possible solutions, Ageing Research Reviews, 9(3), 315–23.CrossRefGoogle ScholarPubMed
Magalhães, J.P. and Toussaint, O. (2004) GenAge: a genomic and proteomic network map of human ageing, FEBS Letters, 571(1–3), 243–7.CrossRefGoogle ScholarPubMed
Dirks, A.J. and Leeuwenburgh, C. (2006) Caloric restriction in humans: potential pitfalls and health concerns, Mechanisms of Ageing and Development, 127(1), 1–7.CrossRefGoogle ScholarPubMed
Dolle, M.E., Giese, H., Hopkins, C.L.et al. (1997) Rapid accumulation of genome rearrangements in liver but not in brain of old mice, Nature Genetics, 17(4), 431–4.CrossRefGoogle Scholar
Esposito, D., Fassina, G., Szabo, P.et al. (1989) Chromosomes of older humans are more prone to aminopterine-induced breakage, Proceedings of the National Academy of Sciences of the USA, 86(4), 1302–6.CrossRefGoogle ScholarPubMed
Finch, C.E. (1990) Longevity, senescence, and the genome. University of Chicago Press.Google Scholar
Finch, C.E. and Ruvkun, G. (2001) The genetics of aging, Annual Review of Genomics and Human Genetics, 2, 435–62.CrossRefGoogle ScholarPubMed
Fontana, L. and Klein, S. (2007) Aging, adiposity, and calorie restriction, Journal of the American Medical Association, 297(9), 986–94.CrossRefGoogle ScholarPubMed
Fontana, L., Meyer, T.E., Klein, S.et al. (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans, Proceedings of the National Academy of Sciences of the USA, 101(17), 6659–63.CrossRefGoogle ScholarPubMed
Friedman, D.B. and Johnson, T.E. (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility, Genetics, 118(1), 75–86.Google ScholarPubMed
Garcia-Cao, I., Garcia-Cao, M., Martin-Caballero, J.et al. (2002) “Super p53” mice exhibit enhanced DNA damage response, are tumor resistant and age normally, EMBO Journal, 21(22), 6225–35.CrossRefGoogle ScholarPubMed
Gardner, E.M. (2005) Caloric restriction decreases survival of aged mice in response to primary influenza infection, Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 60(6), 688–94.CrossRefGoogle ScholarPubMed
George, J.C., Bada, J., Zeh, J.W.et al. (1999) Age and growth estimates of bowhead whales (Balaena mysticetus) via aspartic acid racemization, Canadian Journal of Zoology, 77, 571–80.CrossRefGoogle Scholar
Gosden, R. (1996) Cheating time. New York: W.H. Freeman.Google Scholar
Goto, M. (1997) Hierarchical deterioration of body systems in Werner's syndrome: implications for normal ageing, Mechanisms of Ageing and Development, 98(3), 239–54.CrossRefGoogle ScholarPubMed
Guarente, L. and Kenyon, C. (2000) Genetic pathways that regulate ageing in model organisms, Nature, 408(6809), 255–62.CrossRefGoogle ScholarPubMed
Hagen, T.M., Liu, J., Lykkesfeldt, J.et al. (2002) Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress, Proceedings of the National Academy of Sciences of the USA, 99(4), 1870–5.CrossRefGoogle ScholarPubMed
Hamilton, W.D. (1966) The moulding of senescence by natural selection, Journal of Theoretical Biology, 12(1), 12–45.CrossRefGoogle ScholarPubMed
Hammerman, M.R. (1987) Insulin-like growth factors and aging, Endocrinology and Metabolism Clinics of North America, 16(4), 995–1011.Google ScholarPubMed
Harman, D. (1956) Aging: a theory based on free radical and radiation chemistry, Journal of Gerontology, 11(3), 298–300.CrossRefGoogle ScholarPubMed
Harman, D. (1972) The biologic clock: the mitochondria?, Journal of the American Geriatrics Society, 20(4), 145–7.CrossRefGoogle ScholarPubMed
Harman, D. (1981) The aging process, Proceedings of the National Academy of Sciences of the USA, 78(11), 7124–8.CrossRefGoogle ScholarPubMed
Harper, J.M., Leathers, C.W. and Austad, S.N. (2006) Does caloric restriction extend life in wild mice?, Aging Cell, 5(6), 441–9.CrossRefGoogle ScholarPubMed
Harrison, D.E., Strong, R., Sharp, Z.D.et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice, Nature, 460(7253), 392–5.CrossRefGoogle ScholarPubMed
Hart, R.W. and Setlow, R.B. (1974) Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species, Proceedings of the National Academy of Sciences of the USA, 71(6), 2169–73.CrossRefGoogle Scholar
Hasty, P., Campisi, J., Hoeijmakers, J.et al. (2003) Aging and genome maintenance: lessons from the mouse?, Science, 299(5611), 1355–9.CrossRefGoogle ScholarPubMed
Hayflick, L. (1994) How and why we age. New York: Ballantine Books.Google Scholar
Hayflick, L. and Moorhead, P.S. (1961) The serial cultivation of human diploid cell strains, Experimental Cell Research, 25, 585–621.CrossRefGoogle ScholarPubMed
Heron, M.P., Hoyert, D.L., Jiaquan, X.et al. (2008) Deaths: preliminary data for 2006, National Vital Statistics Reports, 56, 1–52.Google Scholar
Holliday, R. (1995) Understanding ageing. Cambridge University Press.CrossRefGoogle Scholar
Holloszy, J.O. and Smith, E.K. (1986) Longevity of cold-exposed rats: a reevaluation of the “rate-of-living theory”, Journal of Applied Physiology, 61(5), 1656–60.CrossRefGoogle ScholarPubMed
Howitz, K.T., Bitterman, K.J., Cohen, H.Y.et al. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan, Nature, 425(6954), 191–6.CrossRefGoogle ScholarPubMed
Johnson, T.E. (2002) A personal retrospective on the genetics of aging, Biogerontology, 3(1–2), 7–12.CrossRefGoogle ScholarPubMed
Kenyon, C., Chang, J., Gensch, E.et al. (1993) A C. elegans mutant that lives twice as long as wild type, Nature, 366(6454), 461–4.CrossRefGoogle Scholar
Kenyon, C.J. (2010) The genetics of ageing, Nature, 464(7288), 504–12.CrossRefGoogle ScholarPubMed
Kipling, D., Davis, T., Ostler, E.L.et al. (2004) What can progeroid syndromes tell us about human aging?, Science, 305(5689), 1426–31.CrossRefGoogle ScholarPubMed
Kirkwood, T.B. (1977) Evolution of ageing, Nature, 270(5635), 301–4.CrossRefGoogle ScholarPubMed
Kirkwood, T.B. and Austad, S.N. (2000) Why do we age?, Nature, 408(6809), 233–8.CrossRefGoogle ScholarPubMed
Klass, M. and Hirsh, D. (1976) Non-ageing developmental variant of Caenorhabditis elegans, Nature, 260(5551), 523–5.CrossRefGoogle ScholarPubMed
Kujoth, G.C., Hiona, A., Pugh, T.D.et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging, Science, 309(5733), 481–4.CrossRefGoogle ScholarPubMed
Lapointe, J. and Hekimi, S. (2009) When a theory of aging ages badly, Cellular and Molecular Life Sciences, 67, 1–8.
Laron, Z. (2005) Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?, Mechanisms of Ageing and Development, 126(2), 305–7.CrossRefGoogle ScholarPubMed
Lorenzini, A., Tresini, M., Austad, S.N.et al. (2005) Cellular replicative capacity correlates primarily with species body mass not longevity, Mechanisms of Ageing and Development, 126(10), 1130–3.CrossRefGoogle Scholar
MacArthur, R.H. and Wilson, E.O. (1967) The theory of island biogeography. Princeton University Press.Google Scholar
Macintyre, S., Hunt, K. and Sweeting, H. (1996) Gender differences in health: are things really as simple as they seem?, Social Science and Medicine, 42(4), 617–24.CrossRefGoogle Scholar
Martin, G.M. (1978) Genetic syndromes in man with potential relevance to the pathobiology of aging, Birth Defects Original Article Series, 14(1), 5–39.Google Scholar
Martin, G.M. (1982) Syndromes of accelerated aging, National Cancer Institute Monograph, 60, 241–7.Google ScholarPubMed
Martin, G.M., Austad, S.N. and Johnson, T.E. (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses, Nature Genetics, 13(1), 25–34.CrossRefGoogle ScholarPubMed
Martin, G.M. and Oshima, J. (2000) Lessons from human progeroid syndromes, Nature, 408(6809), 263–6.CrossRefGoogle ScholarPubMed
Masoro, E.J. (2005) Overview of caloric restriction and ageing, Mechanisms of Ageing and Development, 126(9), 913–22.CrossRefGoogle ScholarPubMed
Masoro, E.J. (2006) Are age-associated diseases an integral part of aging?, in Masoro, E.J. and Austad, S.N. (eds), Handbook of the biology of aging, 6th edn. San Diego, CA: Academic Press, 43–62.Google Scholar
Matheu, A., Maraver, A., Klatt, P.et al. (2007) Delayed ageing through damage protection by the Arf/p53 pathway, Nature, 448(7151), 375–9.CrossRefGoogle ScholarPubMed
Mattson, M. P., Duan, W. and Maswood, N. (2002) How does the brain control lifespan?, Ageing Research Reviews, 1(2), 155–65.CrossRefGoogle ScholarPubMed
McCay, C.M., Crowell, M.F. and Maynard, L.A. (1935) The effect of retarded growth upon length of the life span and upon the ultimate body size, Journal of Nutrition, 10(1), 63–75.CrossRefGoogle Scholar
Medawar, P.B. (1952) An unsolved problem of biology. London: H.K. Lewis.Google Scholar
Medvedev, Z.A. (1990) An attempt at a rational classification of theories of ageing, Biological Review, 65, 375–98.CrossRefGoogle Scholar
Miller, R.A. (1999) Kleemeier award lecture: are there genes for aging?, Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 54(7), B297–307.CrossRefGoogle ScholarPubMed
Miller, S.E. and Hadfield, M.G. (1990) Developmental arrest during larval life and life-span extension in a marine mollusc, Science, 248(4953), 356–8.CrossRefGoogle Scholar
Mizutani, K., Ikeda, K. and Yamori, Y. (2000) Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats, Biochemical and Biophysical Research Communications, 274(1), 61–7.CrossRefGoogle ScholarPubMed
Nasonkin, I.O., Ward, R.D., Raetzman, L.T.et al. (2004) Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice, Human Molecular Genetics, 13(22), 2727–35.CrossRefGoogle ScholarPubMed
Olshansky, S.J., Hayflick, L. and Carnes, B.A. (2002) No truth to the fountain of youth, Scientific American, 286(6), 92–5.CrossRefGoogle ScholarPubMed
Pearl, R. (1928) The rate of living. New York: Knopf.Google Scholar
Pearson, K.J., Baur, J.A., Lewis, K.N.et al. (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span, Cell Metabolism, 8(2), 157–68.CrossRefGoogle ScholarPubMed
Peto, R. and Doll, R. (1997) There is no such thing as aging, British Medical Journal, 315(7115), 1030–2.CrossRefGoogle ScholarPubMed
Rose, M.R. (1991) Evolutionary biology of aging. New York: Oxford University Press.Google Scholar
Schächter, F., Faure-Delanef, L., Guénot, F.et al. (1994) Genetic associations with human longevity at the APOE and ACE loci, Nature Genetics, 6(1), 29–32.CrossRefGoogle ScholarPubMed
Schriner, S.E., Linford, N.J., Martin, G.M.et al. (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria, Science, 308(5730), 1909–11.CrossRefGoogle Scholar
Smith, P. (2004) Elder care, gender and work: the work–family issue of the 21st century, Berkeley Journal of Employment and Labor Law, 25(2), 352–90.Google Scholar
Sohal, R.S., Mockett, R.J. and Orr, W.C. (2002). Mechanisms of aging: an appraisal of the oxidative stress hypothesis, Free Radical Biology and Medicine, 33(5), 575–86.CrossRefGoogle ScholarPubMed
Speakman, J.R., Talbot, D.A., Selman, C.et al. (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer, Aging Cell, 3(3), 87–95.CrossRefGoogle ScholarPubMed
Stearns, S.C. (1992) The evolution of life histories. Oxford University Press.Google Scholar
Steinert, S., White, D.M., Zou, Y.et al. (2002) Telomere biology and cellular aging in nonhuman primate cells, Experimental Cell Research, 272(2), 146–52.CrossRefGoogle ScholarPubMed
Strehler, B.L. (1999) Time, cells, and aging. Larnaca: Demetriades Brothers.Google Scholar
Suh, Y., Atzmon, G., Cho, M.O.et al. (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians, Proceedings of the National Academy of Sciences of the USA, 105(9), 3438–42.CrossRefGoogle ScholarPubMed
Szilard, L. (1959) On the nature of the aging process, Proceedings of the National Academy of Sciences of the USA, 45(1), 30–45.CrossRefGoogle ScholarPubMed
Tatar, M., Bartke, A. and Antebi, A. (2003) The endocrine regulation of aging by insulin-like signals, Science, 299(5611), 1346–51.CrossRefGoogle ScholarPubMed
Tomas-Loba, A., Flores, I., Fernandez-Marcos, P.J.et al. (2008) Telomerase reverse transcriptase delays aging in cancer-resistant mice, Cell, 135(4), 609–22.CrossRefGoogle ScholarPubMed
Valdesalici, S. and Cellerino, A. (2003) Extremely short lifespan in the annual fish Nothobranchius furzeri, Proceedings. Biological Sciences/The Royal Society, 270 (Suppl 2), S189–91.CrossRefGoogle ScholarPubMed
Remmen, H., Ikeno, Y., Hamilton, M.et al. (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging, Physiological Genomics, 16(1), 29–37.CrossRefGoogle Scholar
Vaupel, J.W., Baudisch, A., Dolling, M.et al. (2004) The case for negative senescence, Theoretical Population Biology, 65(4), 339–51.CrossRefGoogle ScholarPubMed
Wallace, D.C. (1992) Mitochondrial genetics: a paradigm for aging and degenerative diseases?, Science, 256(5057), 628–32.CrossRefGoogle ScholarPubMed
Weindruch, R. and Walford, R.L. (1988) The retardation of aging and disease by dietary restriction. Springfield, IL: C.C. Thomas.Google Scholar
Weismann, A. (1891) On heredity. Oxford: Clarendon Press.Google Scholar
Williams, G.C. (1957) Pleiotropy, natural selection, and the evolution of senescence, Evolution, 11, 398–411.CrossRefGoogle Scholar
Wright, W.E. and Shay, J.W. (2001) Cellular senescence as a tumor-protection mechanism: the essential role of counting, Current Opinion in Genetics and Development, 11(1), 98–103.CrossRefGoogle ScholarPubMed
Yu, C.E., Oshima, J., Fu, Y.H.et al. (1996) Positional cloning of the Werner's syndrome gene, Science, 272(5259), 258–62.CrossRefGoogle ScholarPubMed
Zhou, Z.Q., Manguino, D., Kewitt, K.et al. (2001) Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O6-methylguanine-DNA methyltransferase, Proceedings of the National Academy of Sciences of the USA, 98(22), 12566–71.CrossRefGoogle ScholarPubMed

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