Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-10T16:08:08.441Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic Control of the Aging Process: A Review and Interpretation

Published online by Cambridge University Press:  29 November 2010

Hildegard E. Enesco
Hildegard E. Enesco
Affiliation:
Concordia University
Get access Rights & Permissions [Opens in a new window]

Abstract

The process of aging is under genetic control. The traditional view derived from evolutionary biology is that aging is a polygenic trait, controlled by a large number of genes, each with a small additive effect. An alternative point of view is presented here, which suggests that there may be only a few master genes that control aging. These could include protective genes that ensure accuracy of protein synthesis and protect against free radical damage, as well as genetic control switches that initiate or delay the aging process. As genetic technology advances and the human genome is mapped, our understanding of genes that control aging and age-related diseases may advance to the point that gene therapy becomes possible.

Résumé

Le processus de vieillissement est sous contrôle génétique. Le point de vue traditionnel, dérivé de la biologie évolutive, est que le vieillissement est un trait polygénique, contrôlé par un grand nombre de gènes, chacun avec un effet additif. Un autre point de vue est développé ici, en ajoutant qu'il y a un nombre limité de gènes importants dans le contrôle du vieillissement. Ces derniers peuvent inclure les gènes protecteurs qui assurent l'exactitude de la synthèse de protéines et aussi les gènes qui servent à activer ou à retarder le processus de vieillissement. On continue à développer la technologie génétique afin de faire la carte complète du génome humain. Ces percées offrent la possibilité de comprendre les mécanismes génétiques du vieillissement et même d'envisager la thérapie génétique pour les maladies associées au vieillissement.

Keywords

GenesAging Senescence.Gênesvieillissementsénescence.
Type
Articles
Information
Canadian Journal on Aging / La Revue canadienne du vieillissement , Volume 15 , Issue 1 , Spring/printemps 1996 , pp. 16 - 30
Copyright
Copyright © Canadian Association on Gerontology 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abbott, M., Murphy, E., Bolling, D., & Abbey, H. (1974). The familial component in longevity. A study of offspring of nonagenarians. II Preliminary analysis of the completed study. Johns Hopkins Med. J., 134, 1–16.Google Scholar
Alison, M.R., & Sarraf, C.E. (1992). Apoptosis: a gene-directed programme of cell death. J. Royal College of Phys. London, 26, 25–35.Google Scholar
Arking, R., Dudas, S.P., & Baker, G.T. (1993). Genetic and environmental factors regulating the expression of an extended longevity phenotype in a long lived strain of Drosophila. Genetica, 91, 127–142.Google Scholar
Barinaga, M. (1994). Knockout mice: Round two. Science, 265, 26–28.Google Scholar
Breitner, J.C.S., & Murphy, E.A. (1992). Twin studies of Alzheimer's disease. 2. Some predictions under a genetic model. Amer. J. Hum. Gen., 44, 628–634.CrossRefGoogle Scholar
Campisi, J. (1992). Oncogenes, protooncogenes and tumor suppressor genes: A hitchhiker's guide to senescence? Exp. Gerontol., 27, 397–401.CrossRefGoogle ScholarPubMed
Chen, J.B., Sun, J., & Jazwinksi, S.M. (1990). Prolongation of the yeast life span by the v-Ha-RAS oncogene. Molecular microbiol., 4, 2081–2086.Google Scholar
Dear, K.B.G., Salazar, M., Watson, A.L., Gelman, R.S., Bronson, R., & Yunis, E.J. (1992). Traits that influence longevity in mice: a second look. Genetics, 132, 229–239.CrossRefGoogle ScholarPubMed
D'mello, N.P., Childress, A.M., & Franklin, D.S. (1994). Cloning and characterization of LAGI, a longevity-assurance gene in yeast. J. Biol. Chem., 269, 15451–15459.Google Scholar
Faragher, R.G.A., Kill, I.R., Hunter, J.A., Pope, F.M., Tannock, O., & Shall, S. (1993). The gene responsible for Werner syndrome may be a cell division “counting” gene. Proc. Nat. Acad. Sci., 90, 12030–12034.Google Scholar
Finch, C.E. (1991). Longevity, Senescence and the Genome. Chicago: University of Chicago Press.Google Scholar
Games, D., & 33 collaborators. (1995). Alzheimer-type neuropathology in transgenic mice overexpressing in V717F β-amyloid precursor protein. Nature, 373, 523–527.Google Scholar
Goldstein, S., Murano, S., & Shmookler Reis, R.J. (1990). Werner syndrome; A molecular genetic hypothesis. J. Gerontol., 45, B3–B8.Google Scholar
Goletz, T.J., Hensler, P.J., Ning, Y., Adami, G.R., & Pereira-Smith, O.M. (1993). Evidence for a genetic basis for the model system of cellular senescence. J. Amer. Geriatric Soc., 41, 1255–1258.Google Scholar
Graves, J.L., Toolson, E.C., Jeong, C., Vu, L.N., & Rose, M.R. (1992). Desiccation, flight glycogen, and postponed senescence in Drosophila melanogaster. Physiol. zool., 65, 268–286.Google Scholar
Harding, A.E. (1992). Growing old: the most common mitochondrial disease of all? Nature Genetics, 2, 251–252.Google Scholar
Harley, C.B., Futcher, A.B., & Greider, C.W. (1990). Telomeres shorten during aging of human fibroblasts. Nature, 345, 458–460.Google Scholar
Harley, C.B., Vaziri, H., Counter, C.M., & Allsopp, R.C. (1992). The telomere hypothesis of cellular aging. Exp. Gerontol., 27, 375–382.Google Scholar
Harrison, D.E. (1988). Mini-editorial set: Selection for longer lived rodents. Growth Dev. Aging, 52, 207–211.Google Scholar
Hayflick, L. (1965). The limited in vitro lifespan of human diploid cell strains. Exp. Cell Res., 37, 614–636.CrossRefGoogle Scholar
Hayflick, L. (1992). Aging, longevity, and immortality in vitro. Exp. Gerontol. 27, 363–368.Google Scholar
Hunter, T. (1993). Braking the cycle. Cell, 75, 839–841.Google Scholar
Jazwinski, S.M. (1993). The genetics of aging in the yeast Saccharomyces cerevisiae. Genetica, 91, 35–51.CrossRefGoogle ScholarPubMed
Johnson, T.E. (1990). Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science, 249, 908–912.Google Scholar
Johnson, T.E., and Lithgow, G.J. (1992). The search for the genetic basis of aging: the identification of gerontogenes in the nematode Caenorhabditis elegans. J. Amer. Geriatrics Soc., 40, 936–945.CrossRefGoogle ScholarPubMed
Johnson, T.E., Tedesco, P.M., & Lithgow, G.J. (1993). Comparing mutants, selective breeding and transgenics in the dissection of the aging process of Caenorhabditis elegans. Genetica, 91, 65–77.Google Scholar
Kallman, F.J., & Jarvik, L.F. (1959). Individual differences in constitution and genetic background. In Birren, J.E. (Ed.), Handbook of Aging and the Individual (pp. 216–263). Chicago: University of Chicago Press.Google Scholar
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtlang, R. (1993). A. C. elegans mutant that lives twice as long as wild type. Nature, 366, 461–464.Google Scholar
Kirkwood, T.B.L., & Franceschi, C. (1992). Is aging as complex as it would appear? New perspectives in aging research. Ann. N.Y. Acad. Sci., 663, 412–417.Google Scholar
Kirkwood, T.B.L., & Rose, M.R. (1991). Evolution of senescence: late survival sacrificed for reproduction. Phil. trans. royal soc., 332, 15–24.Google Scholar
Kloeden, P.E., Rossler, R., & Rossler, O.E. (1993). Time-keeping in genetically programmed aging. Exp. Gerontol., 28, 109–118.Google Scholar
Lee, H., Pang, C., Hsu, H., & Wei, U. (1994). Differential accumulation of 4,977 bp deletion in mitochondrial DNA of various tissues in human aging. Biochem. Biophys. Acta., 1226, 37–43.Google Scholar
Luckinbill, L.S. (1990). The role of glucose -6- phosphate dehydrogenase in the evolution of longevity in Drosophila melanogaster. Heredity, 65, 29–38.Google Scholar
Luckinbill, L.S., Arking, R., Clare, M.J., Cirocco, W.C., & Buck, S.A. (1984). Selection for delayed senescence in Drosophila melanogaster. Evolution, 38, 996–1004.Google Scholar
Martin, G.M. (1989). Genetic modulation of the senescent phenotype in Homo sapiens. Genome, 31, 390–397.Google Scholar
Martin, G.M. (1992). Clonal attenuation and cell senescence: the next 30 years. Exp. Gerontol., 27, 455–459.Google Scholar
Martin, G.M. (1993). Abiotrophic gene action in Homo sapiens: potential mechanisms and significance for the pathobiology of aging. Genetica, 91, 265–277.Google Scholar
Martin, G.M., Sprague, C.A., & Epstein, C.J. (1970). Replicative lifespan of cultivated human cells: effect of donor's age and genotype. Lab. Invest., 23, 86–92.Google Scholar
Miguel, J. (1992). An update on the mitochondrial- DNA mutation hypothesis of cell aging. Mut. Res., 275, 209–216.Google Scholar
Mulligan, R.C. (1993). The basic science of gene therapy. Science, 260, 926–931.Google Scholar
Nagley, P., Mackay, I.R., Baumes, A., Maxwell, R.J., Vaillant, F., Wang, Z., Zhang, C., & Linnane, A.W. (1992). Mitochondrial DNA mutation associated with aging and degenerative disease. Ann. N.Y. Acad. Sci., 673, 92–102.CrossRefGoogle ScholarPubMed
Noda, A., Ning, U., Venable, S.F., Pereira-Smith, O.M., & Smith, J.R. (1994). Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res., 211, 90–98.CrossRefGoogle ScholarPubMed
Orr, W.C., & Sohal, R.S. (1993). Effects of Cu-Zn superoxide dismutase overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch. Biochem Biophys., 301, 34–40.Google Scholar
Orr, W.C., & Sohal, R.S. (1994). Extension of life-span by overexpression of super-oxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128–1130.CrossRefGoogle ScholarPubMed
Osiewacz, H.D. (1990). Molecular analysis of aging processes in fungi. Mutation Research, 237, 1–8.Google Scholar
Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C., & Evans, R.M. (1982). Dramatic growth of mice that develop from eggs microinjected with metalothionein-growth hormone fusion genes. Nature, 300, 611–615.Google Scholar
Patel, P.E. (1993). Identification of disease genes and somatic gene therapy: An overview and prospects for the aged. J. Gerontol., 48, B80–85.Google Scholar
Pearl, R., & de Pearl, R.W.. (1934). The Ancestry of the Long-lived. London: H. Milford.Google Scholar
Pendergrass, W.R., Li, Y., Jiang, D., & Wolf, N.S. (1993). Decrease in cellular replicative potential in “giant” mice transfected with the bovine growth hormone gene correlates to shortened lifespan. J. Cell. Physio., 156, 96–103.Google Scholar
Phillips, J.P., Campbell, S.D., Michaud, D., Charbonneau, M., & Hilliker, A. (1989). Null mutation of copper/zinc Superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proc. Nat. Acad. Sci. USA, 86, 2761–2765.Google Scholar
Proust, J., Moulais, R., Fumeron, F., Bekkhoucha, F., Buson, M., Schmid, M., & Hors, J. (1982). HLA and longevity. Tissue Antigens, 19, 168–173.CrossRefGoogle ScholarPubMed
Rattan, S.I.S. (1995. Gerontogenes: real or virtual? FASEB J., 9, 284–286.Google Scholar
Reveillaud, I., Niedzwiecki, A., Bensch, K.G., & Fleming, J.E. (1991). Expression of bovine Superoxide dismutase in Drosophila melanogaster augments resistance to oxidative stress. Mol. Cell Biol., 11, 632–640.Google Scholar
Riabowol, K., Schiff, J., & Gilman, M.Z. (1992). Transcription factor AP-1 activity is required for initiation of DNA synthesis and is lost during cellular aging. Proc. Nat. Acad. Sci. USA, 89, 157–161.CrossRefGoogle ScholarPubMed
Riggs, J.E. (1993). Aging and mortality: manifestations of increasing informational entropy of the genome? Mech. Ageing Dev., 66, 249–256.CrossRefGoogle ScholarPubMed
Rockstein, M. (1958). Heredity and longevity in the animal kingdom. J. Geront., 13, 7–12.Google Scholar
Rose, M.R. (1984). Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution, 38, 1004–1010.Google Scholar
Rose, M.R. (1990). Should mice be selected for postponed aging? Growth Dev. Aging, 54, 7–15.Google Scholar
Rose, M.R., Nusbaum, T.J., & Fleming, J.E. (1992). Drosophila with postponed aging as a model for aging research. Lab. Animal Sci., 42, 114–118.Google Scholar
Sager, R. (1991). Senescence as a mode of tumor suppression. Env. Health Perspect., 93, 59–64.Google Scholar
Sainsard-Chanet, A., Seliem, C., Silar, P., Belcour, L., Dequard-Chablat, M., & Picard, M. (1994). Senescence chez les champignons filamenteux. Médecine/Sciences, 10, 574–576.Google Scholar
Salganik, R.I., Solgovyova, N.A., & Dikalov, S.I. (1994). Inherited enhancement of hydroxyl radical generation and lipid peroxidation in s strain rats results in DNA re-arrangements, degenerative diseases and premature aging. Biochem. Biophys. Res. Comm., 199, 726.Google Scholar
Sassone-Corsi, P. (1994). Rhythmic transcription and autoregulatory loops: Winding up the biological clock. Cell, 78, 361–364.CrossRefGoogle ScholarPubMed
Schachter, F., Cohen, D., & Kirkwood, T. (1993). Prospects for the genetics of human longevity. Human Genetics, 91, 519–526.Google Scholar
Schachter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesseueur-Ginot, L., & Cohen, D. (1994). Genetic associations with human longevity at the APOE and ACE loci. Nature Genetics, 6, 29–32.Google Scholar
Shepherd, J.C.W., Walldorf, U., Hug, P., & Gehring, W.G. (1989). Fruit flies with additional expression of the elongation factor EF-1 live longer. Proc. Nat. Acad. Sci USA, 86, 7520–7521.Google Scholar
Silar, P., & Picard, M. (1994). Increased longevity of the EF-1 high fidelity mutants in Podospora anserina. J. Mol. Biol., 235, 231–236.Google Scholar
Slagboom, P.E., & Vijg, J. (1989). Genetic instability and aging: Theories, facts and future perspectives. Genome, 31, 373–385.Google Scholar
Smith, J.R. (1992). Inhibitors of DNA synthesis derived from senescent human diploid fibroblasts. Exp. Gerontol., 27, 409–412.Google Scholar
Stearns, S.C., & Kaiser, M. (1993). The effects of enhanced expression of elongation factor EF-1 on lifespan in Drosophila melanogaster IV. A summary of three experiments. Genetics, 91, 167–182.Google Scholar
Stellar, H. (1995). Mechanisms and genes of cellular suicide. Science, 267, 1445–1449.CrossRefGoogle Scholar
Swim, H.E. (1957). Microbiological aspects of tissue culture. Ann. Rev. Microbiol., 13, 141–176.Google Scholar
Takagi, Y., Izumi, K., & Kinoshita, H. (1989). Identification of a gene that shortens clonal lifespan of Paramecium tetraaurelia. Genetics, 123, 749.Google Scholar
Takata, H., Suzuki, M., Ishii, T., Sekiguchi, S., & Iri, H. (1987). Influence of major histocompatibility complex region genes on human longevity among Okinawan-Japanese centenarians and nonagenarians. Lancet, II, 824–826.Google Scholar
Tanzi, R., Gaston, S., Bush, A., Romano, D., Pettingell, W., Peppercorn, J., Paradis, M., Gurubhargavatula, S., Jenkins, B., & Wasco, W. (1993). Genetic heterogeneity of gene defects responsible for familial Alzheimer disease. Genetica, 91, 255–263.Google Scholar
Van Duijn, C.M., de Knijff, P., Cruts, M., Wehnert, A., Havekes, L.M., Hofman, A., & van Broeckhoven, C. (1994). Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease. Nature Genetics, 7, 74–78.Google Scholar
Vijg, J., & Papaconstantinou, J. (1990). Aging and longevity genes: Strategies for identifying DNA sequences controlling lifespan. J. Gerontol., 45, B179–182.Google Scholar
Wang, E. (1992). Are all nonproliferating cells similar? Exper. Gerontol., 27, 419–423.CrossRefGoogle ScholarPubMed
White, C.W., Avraham, K.B., Shenley, P.F., & Groner, Y. (1991). Transgenic mice with expression of elevated levels of copper-zinc toxicity. J. Clin. Invest., 87, 2162–2168.Google Scholar
Wilson, R., & 54 collaborators. (1994). 2.2 Mb of continuous nucleotide sequence from chromosome III of C. elegans. Nature, 368, 32–38.Google Scholar
Wood, W.B., & Johnson, T.E. (1994). Stopping the clock. Current Biology, 4, 151–153.Google Scholar
Zuckerkandl, E. (1993). Can flies stand in for humans? J. Mol. Evol., 37, 1–4.Google Scholar