Abstract
Aging is controlled by a complex interplay of both genetic and environmental factors. Because of this, many theories have been advanced that seek to explain the etiology of both cellular and organismal aging (Jazwinski 1996; Holliday 1997). In some cases, these theories are not mutually exclusive. One particularly popular theory posits that free radicals, especially those of molecular oxygen, can accelerate aging (Harman 1986). Martin et al. (1996) have eloquently articulated seven different classes of genetic loci that could modulate aging through oxidative damage. These include, for example, genes that would affect the generation of free radicals and others that modulate the scavenging of free radicals. A third class is those genes that specify repair enzymes. In addition, Cutler (1985) summarized a variety of data that support the notion that oxidative damage impacts aging. These include correlations between either free radical production or defenses against free radicals as compared with aging or life span. For example, the product of the standard metabolic rate and the maximum life span is roughly constant for various animals, indicating that animals with lower standard metabolic rates can live for longer periods than animals with higher rates. This concept, called the LEP (life-span energy potential), strongly suggests that oxygen radicals may exacerbate aging. More directly, the concentration of antioxidants in various mammalian tissues is inversely related to their maximum life-span potential (MLSP).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Adachi H, Fujiwara Y, Ishii N (1998) Effects of oxygen on protein carbonyl and aging in Caenorhabditis elegans mutants with long (age-1) and short (mev-1) life spans. J Geront Biol Sci 53A: B240 - B244
Bagley AC, Krall J, Lynch RE (1986) Superoxide meditates the toxicity of paraquat for Chinese hamster ovary cells. Proc Natl Acad Sci USA 93: 3189–3193
Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Peqignot E, Munnich A, Rotig A (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 11: 144–149
Carlsson LM, Jonsson J, Edlund T, Marklund SL (1995) Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc Natl Acad Sci USA 92: 6264–6268
C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282: 2012–2018
Chen Q, Ficher A, Reagan JD, Yan L-J, Ames BN (1995) Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci USA 92: 4337–4341
Cutler RG (1985) Antioxidants and longevity of mammalian species. In: Woodland AD, Blackett AD, Hollaender A (eds) Molecular biology of aging. Plenum Press, New York pp 15–73
Epstein J, Himmelhoch S, Gershon D (1972) Studies on aging in nematodes. III. Electron microscopical studies on age-associated cellular damage. Mech Ageing Dev 1: 245–255
Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S (1997) Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275: 980–983
Friedman DB, Johnson TE (1988a) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118: 75–86
Friedman DB, Johnson TE (1988b) Three mutants that extended both mean and maximum lie span of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol Biol Sci 43: B102 - B109
Gems D, Riddle DR (1996) Longevity in Caenorhabditis elegans reduced by mating but not gamete production. Nature 379: 723–725
Grollman AP, Moriya M (1993) Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet 9: 246–249
Harman D (1986) Free radical theory of aging: effect of free radical reaction inhibitors on the mortality rate of male LAF mice. J Gerontol 23: 476–482
Hartman PS, Herman RK (1982) Radiation-sensitive mutants of Caenorhabditis elegans. Genetics 102: 159–178
Hartman PS, DeWilde D, Dwarakanath V (1995) Genetic and molecular analyses of UV radiation-induced mutations in the fem-3 gene of Caenorhabditis elegans. Photochem Photobiol 61: 607–614
Hengartner MO, Horvitz HR (1994) C. elegans cell survival gene ced-9 encodes a functional homologue of the mammalian proto-oncogene bc1–2. Cell 76: 665–676
Holliday R (1997) Understanding aging. Philos Trans R Soc Lond B Biol Sci 352: 1793–1797
Honda S, Ishii N, Suzuki K, Matsuo M (1993) Oxygen-dependent perturbation of life span and aging rate in the nematode. J Gerontol Biol Sci 48: B57 - B61
Hosokawa H, Ishii N, Ishida H, Ichimori K, Nakazawa H, Suzuki K (1994) Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech Ageing Dev 74: 161–170
Ishii N, Takahashi K, Tornita S, Keino T, Honda S, Yoshino K, Suzuki K (1990) A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat Res 237: 165–171
Ishii N, Suzuki N, Hartman PS, Suzuki K (1993) The radiation-sensitive mutant rad-8 of Caenorhabditis elegans is hypersensitive to the effects of oxygen on aging and development. Mech Ageing Dev 68: 1–10
Ishii N, Suzuki N, Hartman PS, Suzuki K (1994) The effects of temperature-sensitive mutant rad-8 of the nematode Caenorhabditis elegans. J Gerontol Biol Sci 49: B117 - B120
Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394: 694–697
Jazwinski SM (1996) Longevity, genes, and aging. Science 273: 54–59
Johnson TE, Wood WB (1982) Genetic analysis of life span in Caenorhabditis elegans. Proc Natl Acad Sci USA 79: 6603–6607
Jonassen T, Proft M, Randez-Gil F, Schultz JR, Marbois BN, Entian K-D, Clarke CF (1998) Yeast clk-1 homologue (cog7/cats) is a mitochondrial protein in coenzyme Q. J Biol Chem 273: 3351–3357
Kenyon C, Chang J, Gensch E, Rudner A, Tabtang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366: 461–464
Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277: 942–946
Kluck CN, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bd-2 regulation of apoptosis. Science 275: 1132–1136
Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90: 8905–8909
Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11: 376–381
Lieberthal W, Menza SA, Levine JS (1998) Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells. Am J Physiol 274: F315 - F327
Martin GM (1978) Genetic syndromes in man with relevance to the pathology of aging. In: Bergsma D, Harrison DE (eds) Genetic effects on aging, birth defects. Original Article Series vol 14, Alan R Liss, New York, pp 5–39
Martin GM (1991) Genetic and environmental modulations of chromosomal stability: their roles in aging and oncogenesis. Ann NY Acad Sci 621: 401–417
Martin GM, Austad SN, Johnson TE (1996) Genetic analysis of ageing: role of oxidative damages and environmental stresses: review. Nat Genet 13: 25–33
Marton A, Mihalik R, Bratincsak A, Adleff V, Petak I, Vegh M, Bauer PI, Krajcsi P (1997) Apoptotic cell death induced by inhibitors of energy conservation Bd-2 inhibits apoptosis downstream of a fall of ATP level. Eur J Biochem 250: 467–475
Mignotte B, Vayssiere J-L (1998) Mitochondria and apoptosis: review. Eur J Biochem 252: 1–15
Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382: 536–539 Miller LJ, Marx J (1998) Apoptosis. Science 281: 1301–1326
Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143: 1207–1218
Orr WC, Sohal RS (1994) Extension of life span by over expression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263: 1128–1130
Reaume AG, Elliott J, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH Jr, Scott RW, Snider WD (1996) Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet 13: 43–47
Riddle DL, Blumenthal T, Mayer BJ, Priess JR (eds) (1997) C. elegans II. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91: 10771–10778
Stadman ER (1992) Protein oxidation and aging. Science 257: 1220–1224
Stadman ER, Oliver CN (1991) Metal-catalyzed oxidation of proteins. J Biol Chem 266: 20052008
Strehler BL, Mark DD, Mildvan AS, Gee MV (1959) Rate and magnitude of age pigment accumulation in the human myocardium. J Gerontol 14: 257–264
Sugioka K, Nakano M, Totsune-Nakano H, Minakami H, Tero-Kubota S, Ikegami Y (1988) Mechanism of 02-generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems. Biochem Biophys Acta 936: 377–385
Turrens JF, Boveris A (1981) Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 191: 421–427
Turrens JF, Alexandre A, Lehninger AL (1985) Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. Arch Biochem Biophys 237: 408–414
Vanfleteren JR (1993) Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 292: 605–608
Van Voorthies WA (1992) A production of sperm reduces nematode lifespan. Nature 360: 456–458
Wong A, Boutis PA, Hekimi S (1995) Mutations in the clk-1 gene of Caenorhabditis elegans affect development and behavioral timing. Genetics 139: 1247–1259
Wood WB (ed) (1988) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
Yamamoto K, Honda S, Ishii N (1996) Properties of an oxygen-sensitive mutant mev-3 of the nematode Caenorhabditis elegans. Mutat Res 358: 1–6
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bd-2: release of cytochrome c from mitochondrial block. Science 257: 1129–1132
Yasuda K, Adachi F, Fujiwara Y, Ishii N (1999) Protein carbonyl accumulation in aging dauer formation-defective (daft mutants of Caenorhabditis elegans. J Gerontol Biol Sci 54A: B47 - B51
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ishii, N., Hartman, P.S. (2000). Oxidative Stress and Aging in Caenorhabditis elegans . In: Hekimi, S. (eds) The Molecular Genetics of Aging. Results and Problems in Cell Differentiation, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-48003-7_8
Download citation
DOI: https://doi.org/10.1007/978-3-540-48003-7_8
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-53686-1
Online ISBN: 978-3-540-48003-7
eBook Packages: Springer Book Archive