The Unfortunate Influence of the Weather on the Rate of Ageing: Why Human Caloric Restriction or Its Emulation May Only Extend Life Expectancy by 2–3 Yearsde Grey A.D.N.J.
Department of Genetics, University of Cambridge, Cambridge, UK
Dr. Aubrey D.N.J. de Grey
Department of Genetics, University of Cambridge, Downing Street
Cambridge CB2 3EH (UK)
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Much research interest, and recently even commercial interest, has been predicated on the assumption that reasonably closely-related species – humans and mice, for example – should, in principle, respond to ageing-retarding interventions with an increase in maximum lifespan roughly proportional to their control lifespan (that without the intervention). Here, it is argued that the best-studied life-extending manipulations of mice are examples of a category that is highly unlikely to follow this rule, and more likely to exhibit only a similar absolute increase in maximum lifespan from one species to the next, independent of the species’ control lifespan. That category – reduction in dietary calories or in the organism’s ability to metabolize or sense them – is widely recognized to extend lifespan as an evolutionary adaptation to transient starvation in the wild, a situation which alters the organism’s optimal partitioning of resources between maintenance and reproduction. What has been generally overlooked is that the extent of the evolutionary pressure to maintain adaptability to a given duration of starvation varies with the frequency of that duration, something which is – certainly for terrestrial animals and less directly for others – determined principally by the weather. The pattern of starvation that the weather imposes is suggested here to be of a sort that will tend to cause all terrestrial animals, even those as far apart phylogenetically as nematodes and mice, to possess the ability to live a similar maximum absolute (rather than proportional) amount longer when food is short than when it is plentiful. This generalization is strikingly in line with available data, leading (given the increasing implausibility of further extending human mean but not maximum lifespan in the industrialized world) to the biomedically and commercially sobering conclusion that interventions which manipulate caloric intake or its sensing are unlikely ever to confer more than 2 or 3 years’ increase in human mean or maximum lifespan at the most.
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McCay CM, Crowell MF, Maynard LA: The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 1935;10:63–79.
- Klass MR: Aging in the nematode Caenorhabditis elegans: Major biological and environmental factors influencing life span. Mech Ageing Dev 1977;6:413–429.
- Riddle DL, Swanson MM, Albert PS: Interacting genes in nematode dauer larva formation. Nature 1981;290:668–671.
- Klass M, Hirsh D: Non-ageing developmental variant of Caenorhabditis elegans. Nature 1976;260:523–525.
- Arantes-Oliveira N, Berman JR, Kenyon C: Healthy animals with extreme longevity. Science 2003;302:611.
- Larsen PL, Clarke CF: Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 2002;295:120–123.
- Lumme J, Oikarinen A, Lakovaara S, Alatalo R: The environmental regulation of adult diapause in Drosophila littoralis. J Insect Physiol 1974;20:2023–2033.
- Tatar M, Yin C: Slow aging during insect reproductive diapause: Why butterflies, grasshoppers and flies are like worms. Exp Gerontol 2001;36:723–738.
Uvarov B: Hibernation of active stages of Acridoidea in temperate climates. Atti Acad Gioenia Sci Nat 1966;6:175–189.
- Weindruch R, Walford RL, Fligiel S, Guthrie D: The retardation of aging in mice by dietary restriction: Longevity, cancer, immunity and lifetime energy intake. J Nutr 1986;116:641–654.
- Kealy RD, Lawler DF, Ballam JM, Mantz SL, Biery DN, Greeley EH, Lust G, Segre M, Smith GK, Stowe HD: Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc 2002;220:1315–1320.
- Pinney DO, Stephens DF, Pope LS: Lifetime effects of winter supplemental feed level and age at first parturition on range beef cows. J Anim Sci 1972;34:1067–1077.
Weismann A: Essays upon Heredity and Kindred Biological Problems, ed 2. Oxford, Clarendon Press, 1891, vol 1.
Medawar PB: An Unsolved Problem in Biology. London, Lewis, 1952.
- Williams GC: Pleiotropy, natural selection and the evolution of senescence. Evolution 1957;11:398–411.
- Edney EB, Gill RW: Evolution of senescence and specific longevity. Nature 1967;220:281–282.
- Austad SN: Retarded senescence in an insular population of Virginia opossums (Didelphis virginiana). J Zool 1993;229:695–708.
- Kirkwood TBL: Evolution of ageing. Nature 1977;270:301–304.
- Karahalil B, Hogue BA, de Souza-Pinto NC, Bohr VA: Base excision repair capacity in mitochondria and nuclei: Tissue-specific variations. FASEB J 2002;16:1895–1902.
- Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L: Mammalian SIRT1 represses forkhead transcription factors. Cell 2004;116:551–563.
- Harrison DE, Archer JR: Natural selection for extended longevity from food restriction. Growth Dev Aging 1988;52:65.
- Holliday R: Food, reproduction and longevity: Is the extended lifespan of calorie-restricted animals an evolutionary adaptation? Bioessays 1989;10:125–127.
- Bauer M, Hamm AC, Bonaus M, Jacob A, Jaekel J, Schorle H, Pankratz MJ, Katzenberger JD: Starvation response in mouse liver shows strong correlation with life-span-prolonging processes. Physiol Genomics 2004;17:230–244.
- Westendorp RG: Leiden research program on ageing. Exp Gerontol 2002;37:609–614.
- Westendorp RG, van Dunne FM, Kirkwood TB, Helmerhorst FM, Huizinga TW: Optimizing human fertility and survival. Nat Med 2001;7:873.
- Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafe M, Cavallone L, Marchegiani F, Olivieri F, Franceschi C, Caruso C: Inflammation, genetics, and longevity: Further studies on the protective effects in men of IL-10-1082 promoter SNP and its interaction with TNF-alpha-308 promoter SNP. J Med Genet 2003;40:296–299.
- Rose MR: Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution 1984;38:1004–1010.
- Crespi BJ, Teo R: Comparative phylogenetic analysis of the evolution of semelparity and life history in salmonid fishes. Evolution Int J Org Evolution 2002;56:1008–1020.
Holliday R: Understanding Ageing. Cambridge, Cambridge University Press, 1995.
Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BC: Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol A Biol Sci Med Sci 2003;58:212–219.
Masoro EJ: Subfield history: Caloric restriction, slowing aging, and extending life. Sci Aging Knowl Environ 2003;2003:RE2.
- Lin YJ, Seroude L, Benzer S: Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 1998;282:943–946.
- Rogina B, Reenan RA, Nilsen SP, Helfand SL: Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 2000;290:2137–2140.
- Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L: Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 2001;292:104–106.
- Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS: A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 2001;292:107–110.
Herman WS, Tatar M: Juvenile hormone regulation of longevity in the migratory monarch butterfly. Proc R Soc Lond B Biol Sci 2001;268:2509–2514.
Bartke A, Coschigano K, Kopchick J, Chandrashekar V, Mattison J, Kinney B, Hauck S: Genes that prolong life: Relationships of growth hormone and growth to aging and life span. J Gerontol A Biol Sci Med Sci 2001;56:B340–B349
- Hsin H, Kenyon C: Signals from the reproductive system regulate the lifespan of C. elegans. Nature 1999;399:362–366.
- Fontana L, Meyer TE, Klein S, Holloszy JO: Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci USA 2004;101:6659–6663.
- Yashin AI, Begun AS, Boiko SI, Ukraintseva SV, Oeppen J. The new trends in survival improvement require a revision of traditional gerontological concepts. Exp Gerontol 2001;37:157–167.
Stuart M: The genomics of longevity. Windhover’s Rev Emerg Med Ventures 2003;8:22.
Guarente L: Ageless Quest. New York, Cold Spring Harbor Laboratory Press, 2003.