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. 2000 Nov;197(Pt 4):521–528. doi: 10.1046/j.1469-7580.2000.19740521.x

An integrated theory of ageing in the nematode Caenorhabditis elegans

DAVID GEMS 1,✉
PMCID: PMC1468166  PMID: 11197524

Abstract

Numerous theories of ageing have been proposed, and many have been tested experimentally, particularly using nematode models such as Caenorhabditis elegans. By combining those theories of ageing that remain plausible with recent findings from studies of C. elegans life span mutants, an integrated theory of ageing has been devised. This is formed from 3 interconnected elements: the evolutionary theory of ageing, the oxidative damage theory of ageing, and a nonadaptive programmed ageing theory. This tripartite theory of ageing gives rise to a number of predictions that may be tested experimentally.

Keywords: Theories of ageing, oxidative damage, programmed ageing, evolutionary theory of ageing, Caenorhabditis elegans , nematode

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Selected References

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  1. Brooks A., Johnson T. E. Genetic specification of life span and self-fertility in recombinant-inbred strains of Caenorhabditis elegans. Heredity (Edinb) 1991 Aug;67(Pt 1):19–28. doi: 10.1038/hdy.1991.60. [DOI] [PubMed] [Google Scholar]
  2. Edney E. B., Gill R. W. Evolution of senescence and specific longevity. Nature. 1968 Oct 19;220(5164):281–282. doi: 10.1038/220281a0. [DOI] [PubMed] [Google Scholar]
  3. Fabian T. J., Johnson T. E. Identification genes that are differentially expressed during aging in Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci. 1995 Sep;50(5):B245–B253. doi: 10.1093/gerona/50a.5.b245. [DOI] [PubMed] [Google Scholar]
  4. Friedman D. B., Johnson T. E. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics. 1988 Jan;118(1):75–86. doi: 10.1093/genetics/118.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gems D., Riddle D. L. Longevity in Caenorhabditis elegans reduced by mating but not gamete production. Nature. 1996 Feb 22;379(6567):723–725. doi: 10.1038/379723a0. [DOI] [PubMed] [Google Scholar]
  6. Gems D., Sutton A. J., Sundermeyer M. L., Albert P. S., King K. V., Edgley M. L., Larsen P. L., Riddle D. L. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics. 1998 Sep;150(1):129–155. doi: 10.1093/genetics/150.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. HARMAN D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul;11(3):298–300. doi: 10.1093/geronj/11.3.298. [DOI] [PubMed] [Google Scholar]
  8. Harrington L. A., Harley C. B. Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev. 1988 Apr;43(1):71–78. doi: 10.1016/0047-6374(88)90098-x. [DOI] [PubMed] [Google Scholar]
  9. Hartman P. S., Simpson V. J., Johnson T., Mitchell D. Radiation sensitivity and DNA repair in Caenorhabditis elegans strains with different mean life spans. Mutat Res. 1988 Jun;208(2):77–82. doi: 10.1016/s0165-7992(98)90003-3. [DOI] [PubMed] [Google Scholar]
  10. Hekimi S., Lakowski B., Barnes T. M., Ewbank J. J. Molecular genetics of life span in C. elegans: how much does it teach us? Trends Genet. 1998 Jan;14(1):14–20. doi: 10.1016/S0168-9525(97)01299-7. [DOI] [PubMed] [Google Scholar]
  11. Helfand S. L., Blake K. J., Rogina B., Stracks M. D., Centurion A., Naprta B. Temporal patterns of gene expression in the antenna of the adult Drosophila melanogaster. Genetics. 1995 Jun;140(2):549–555. doi: 10.1093/genetics/140.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hengartner M. O. Genetic control of programmed cell death and aging in the nematode Caenorhabditis elegans. Exp Gerontol. 1997 Jul-Oct;32(4-5):363–374. doi: 10.1016/s0531-5565(96)00167-2. [DOI] [PubMed] [Google Scholar]
  13. Honda S., Ishii N., Suzuki K., Matsuo M. Oxygen-dependent perturbation of life span and aging rate in the nematode. J Gerontol. 1993 Mar;48(2):B57–B61. doi: 10.1093/geronj/48.2.b57. [DOI] [PubMed] [Google Scholar]
  14. Hosokawa H., Ishii N., Ishida H., Ichimori K., Nakazawa H., Suzuki K. Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech Ageing Dev. 1994 Jun;74(3):161–170. doi: 10.1016/0047-6374(94)90087-6. [DOI] [PubMed] [Google Scholar]
  15. Ishii N., Takahashi K., Tomita S., Keino T., Honda S., Yoshino K., Suzuki K. A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat Res. 1990 May-Jul;237(3-4):165–171. doi: 10.1016/0921-8734(90)90022-j. [DOI] [PubMed] [Google Scholar]
  16. Johnson T. E., McCaffrey G. Programmed aging or error catastrophe? An examination by two-dimensional polyacrylamide gel electrophoresis. Mech Ageing Dev. 1985 May 31;30(3):285–297. doi: 10.1016/0047-6374(85)90118-6. [DOI] [PubMed] [Google Scholar]
  17. Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993 Dec 2;366(6454):461–464. doi: 10.1038/366461a0. [DOI] [PubMed] [Google Scholar]
  18. Kirkwood T. B., Rose M. R. Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci. 1991 Apr 29;332(1262):15–24. doi: 10.1098/rstb.1991.0028. [DOI] [PubMed] [Google Scholar]
  19. Klass M., Hirsh D. Non-ageing developmental variant of Caenorhabditis elegans. Nature. 1976 Apr 8;260(5551):523–525. doi: 10.1038/260523a0. [DOI] [PubMed] [Google Scholar]
  20. Lakowski B., Hekimi S. Determination of life-span in Caenorhabditis elegans by four clock genes. Science. 1996 May 17;272(5264):1010–1013. doi: 10.1126/science.272.5264.1010. [DOI] [PubMed] [Google Scholar]
  21. Lakowski B., Hekimi S. The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13091–13096. doi: 10.1073/pnas.95.22.13091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Larsen P. L. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8905–8909. doi: 10.1073/pnas.90.19.8905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Larsen P. L., Albert P. S., Riddle D. L. Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics. 1995 Apr;139(4):1567–1583. doi: 10.1093/genetics/139.4.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Medvedev Z. A. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990 Aug;65(3):375–398. doi: 10.1111/j.1469-185x.1990.tb01428.x. [DOI] [PubMed] [Google Scholar]
  25. Meheus L. A., Van Beeumen J. J., Coomans A. V., Vanfleteren J. R. Age-specific nuclear proteins in the nematode worm Caenorhabditis elegans. Biochem J. 1987 Jul 1;245(1):257–261. doi: 10.1042/bj2450257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murakami S., Johnson T. E. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics. 1996 Jul;143(3):1207–1218. doi: 10.1093/genetics/143.3.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. ORGEL L. E. The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc Natl Acad Sci U S A. 1963 Apr;49:517–521. doi: 10.1073/pnas.49.4.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ono T., Cutler R. G. Age-dependent relaxation of gene repression: increase of endogenous murine leukemia virus-related and globin-related RNA in brain and liver of mice. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4431–4435. doi: 10.1073/pnas.75.9.4431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Orr W. C., Sohal R. S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science. 1994 Feb 25;263(5150):1128–1130. doi: 10.1126/science.8108730. [DOI] [PubMed] [Google Scholar]
  30. Parkes T. L., Elia A. J., Dickinson D., Hilliker A. J., Phillips J. P., Boulianne G. L. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet. 1998 Jun;19(2):171–174. doi: 10.1038/534. [DOI] [PubMed] [Google Scholar]
  31. Partridge L., Barton N. H. Optimality, mutation and the evolution of ageing. Nature. 1993 Mar 25;362(6418):305–311. doi: 10.1038/362305a0. [DOI] [PubMed] [Google Scholar]
  32. Plaisier A. P., van Oortmarssen G. J., Remme J., Habbema J. D. The reproductive lifespan of Onchocerca volvulus in West African savanna. Acta Trop. 1991 Feb;48(4):271–284. doi: 10.1016/0001-706x(91)90015-c. [DOI] [PubMed] [Google Scholar]
  33. Rogina B., Benzer S., Helfand S. L. Drosophila drop-dead mutations accelerate the time course of age-related markers. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6303–6306. doi: 10.1073/pnas.94.12.6303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rogina B., Helfand S. L. Timing of expression of a gene in the adult Drosophila is regulated by mechanisms independent of temperature and metabolic rate. Genetics. 1996 Aug;143(4):1643–1651. doi: 10.1093/genetics/143.4.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rogina B., Vaupel J. W., Partridge L., Helfand S. L. Regulation of gene expression is preserved in aging Drosophila melanogaster. Curr Biol. 1998 Apr 9;8(8):475–478. doi: 10.1016/s0960-9822(98)70184-8. [DOI] [PubMed] [Google Scholar]
  36. Roy A. K. Transcription factors and aging. Mol Med. 1997 Aug;3(8):496–504. [PMC free article] [PubMed] [Google Scholar]
  37. Sohal R. S., Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996 Jul 5;273(5271):59–63. doi: 10.1126/science.273.5271.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sun J., Tower J. FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol. 1999 Jan;19(1):216–228. doi: 10.1128/mcb.19.1.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Targovnik H. S., Locher S. E., Hart T. F., Hariharan P. V. Age-related changes in the excision repair capacity of Turbatrix aceti. Mech Ageing Dev. 1984 Sep;27(1):73–81. doi: 10.1016/0047-6374(84)90083-6. [DOI] [PubMed] [Google Scholar]
  40. Taub J., Lau J. F., Ma C., Hahn J. H., Hoque R., Rothblatt J., Chalfie M. A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature. 1999 May 13;399(6732):162–166. doi: 10.1038/20208. [DOI] [PubMed] [Google Scholar]
  41. Vanfleteren J. R., De Vreese A. Analysis of the proteins of aging Caenorhabditis elegans by high resolution two-dimensional gel electrophoresis. Electrophoresis. 1994 Feb;15(2):289–296. doi: 10.1002/elps.1150150149. [DOI] [PubMed] [Google Scholar]
  42. Vanfleteren J. R., De Vreese A. The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J. 1995 Oct;9(13):1355–1361. doi: 10.1096/fasebj.9.13.7557026. [DOI] [PubMed] [Google Scholar]
  43. Vanfleteren J. R. Oxidative stress and ageing in Caenorhabditis elegans. Biochem J. 1993 Jun 1;292(Pt 2):605–608. doi: 10.1042/bj2920605. [DOI] [PMC free article] [PubMed] [Google Scholar]

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