Abstract
At least three mechanisms determine life span in Caenorhabditis elegans. An insulin-like signaling pathway regulates dauer diapause, reproduction and longevity. Reduction-or loss-of-function mutations in this pathway can extend longevity substantially, suggesting that the wild-type alleles shorten life span. The mutations extend life span by activating components of a dauer longevity assurance program in adult life, resulting in altered metabolism and enhanced stress resistance. The Clock (Clk) genes regulate many temporal processes, including life span. Mutation in the Clk genes clk-1 and gro-1 mildly affect energy production, but repress energy consumption dramatically, thereby reducing the rate of anabolic metabolism and lengthening life span. Dietary restriction, either imposed by mutation or by the culture medium increases longevity and uncovers a third mechanism of life span determination. Dietary restriction likely elicits the longevity assurance program. There is still uncertainty as to whether these pathways converge on daf-16 to activate downstream longevity effector genes such as ctl-1 and sod-3.
There is overwhelming evidence that the interplay between reactive oxygen species (ROS) and the capacity to resist oxidative stress controls the aging process and longevity. It is as yet not clear whether metabolic homeostasis collapses with age as a direct result of ROS-derived damage or is selectively repressed by longevity-determining genes. The dramatic decline of protein turnover during senescence results in the accumulation of altered enzymes and in a gradual decline of metabolic performance eventually followed by fatal failure of the system.
Similar content being viewed by others
References
Adachi, H, Fujiwara, Y, and Ishii, N: Effects of oxygen on protein carbonyl and aging in Caenorhabditis elegans mutants with long (age-1) and short (mev-1) life spans. J. Gerontol. Biol. Sci., 53: B240–B244, 1998.
Ailion, M, Inoue, T, Weaver, CI, Holdcraft, RW, and Thomas, JH: Neurosecretory control of aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 96: 7394–7397, 1999.
Anderson, GL: Responses of dauer larvae of Caenorhabditis elegans (Nematoda: Rhabditidae) to thermal stress and oxygen deprivation. Can. J. Zool., 56: 1786–1791, 1978.
Anderson, GL: Superoxide dismutase activity in the dauer larvae of Caenorhabditis elegans. Can. J. Zool., 60:288–291, 1982.
Apfeld, J, and Kenyon, C: Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell, 95:199–210, 1998.
Arking, R: Biology of aging: Observations and principles. Sunderland, Massachusetts, Sinauer Associates, 1998.
Bartke, A, Brown-Borg, HM, Bode, AM, Carlson, J, Hunter, WS, and Bronson, RT: Does growth hormone prevent or accelerate aging? Exp. Gerontol., 33:675–687, 1998.
Bolanowski, MA, Jacobson LA, and Russell, RL: Quantitative measures of aging in the nematode Caenorhabditis elegans. II. Lysosomal hydrolases as markers of senescence. Mech. Ageing Dev., 21:295–319, 1983.
Braeckman, BP, Houthoofd, K, De Vreese, A, and Vanfleteren, JR: Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans. Curr. Biol., 9:493–496, 1999.
Brown-Borg, HM, Borg, KE, Meliska, CJ, and Bartke, A: Dwarf mice and the ageing process. Nature, 384: 33, 1996.
Dalley, BK, and Golomb, M: Gene expression in the Caenorhabiditis elegans dauer larva: Developmental regulation of Hsp90 and other genes. Dev. Biol., 151:80–90, 1992.
De Cuyper, C, and Vanfleteren, JR: Oxygen consumption during development and aging of the nematode Caenorhabditis elegans. Comp. Biochem. Physiol., 73A: 283–289, 1982.
Dukan, S, and Nyström, T: Bacterial senescence: stasis results in increased and differential oxidation of cytoplasmic proteins leading to developmental induction of the heat shock regulon. Genes Dev., 12:3431–3441, 1998.
Epstein, HF, and Shakes, DC: Methods in Cell Biology Vol 48: Caenorhabditis elegans. Modern Biological Analysis of an Organism, series edited by Wilson, L, and Matsudaira, P, New York, Academic Press, 1995.
Ewbank, JJ, Barnes, TM, Lakowski, B, Lussier, M, Bussey, H, and Hekimi, S: Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science, 275:980–983, 1997.
Fabian, TE, and Johnson, TE: Production of age-synchronous mass cultures of Caenorhabditis elegans. J. Gerontol. Biol. Sci., 49: B145–B156, 1994.
Faulkner, K, and Fridovich, I: Luminol and Lucigenin as detectors for O2 −. Free Rad. Biol. Med., 15: 447–451, 1993.
Felkai, S, Ewbank, JJ, Lemieux, J, Labbé J-C, Brown, GG, and Hekimi, S: CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans. EMBO J., 18:1783–1792, 1999.
Feuers, RJ, Duffy, PH, Chen, F, Desai, V, Oriaku, E, Shaddock, JG, Pipkin, JW, Weindruch, R, and Hart, RW: Intermediary metabolism and antioxidant systems, in Dietary restriction: Implications for the design and interpretation of toxicity and carcinogeneticy studies, eidted by Hart, RW, Neumann, DA, and Robertson, RT, Washington, DC, ILSI Press, 1995, pp. 180–195.
Finch, C: Longevity, Senescence, and the Genome. Chicago, The University of Chicago Press, 1990, pp. 281–282.
Friedman, DB, and Johnson, TE: A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics, 118:75–86, 198a.
Friedman, DB, and Johnson, TE: Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene. J. Gerontol., 34:B102–B109, 1988b.
Fujii, M, Ishii, N, Joguchi, A, Yasuda, K, and Ayusawa, D: A novel superoxide dismutase gene encoding membrane-bound and extracellular isoforms by alternative splicing in Caenorhabditis elegans. DNA Res., 5: 25–30, 1998.
Gabius, H-J, Graupner, G, and Cramer, F: Activity of aminoacyl-tRNA synthetases, tRNA methylases, arginyltransferase and tubulin:tyrosine ligase during development and ageing of Caenorhabditis elegans. Eur. J. Biochem., 131: 231–234, 1983.
Gems, D, Sutton, AJ, Sundermeyer, ML, Albert, PS, King, KV, Edgley, ML, Larsen, PL, and Riddle, DL: Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics, 150:129–155, 1998.
Giglio, AM, Hunter, T, Bannister, JV, Bannister, WH, and Hunter, GJ: The copper/zinc superoxide dismutase gene of Caenorhabditis elegans. Biochem. Mol. Biol. Int., 33:41–44, 1994a.
Giglio, MP, Hunter, T, Bannnister, JV, Bannister, WH, and Hunter, GJ: The managanese superoxide dismutase gene of Caenorhabditis elegans. Biochem. Mol. Biol. Int., 33:37–40, 1994b.
Goren, P, Reznick, AZ, Reiss, U, and Gershon, D: Isoelectric properties of nematode aldolase and rat liver superoxide dismutase from young and old animals. FEBS Lett., 84: 83–86, 1977.
Gottlieb, S, and Ruvkun, G: daf-2, daf-16 and daf-23: Genetically interacting genes controlling dauer formation in Caenorhabditis elegans. Genetics, 137: 107–120, 1994.
Guarente, L, Ruvkun, G, and Amasino, R: Aging, life span, and senescence. Proc. Natl. Acad. Sci. USA, 95: 11034–11036, 1998.
Gupta, SK, and Rothstein, M: Phosphoglycerate kinase from young and old Turbatrix aceti. Biochim. Biophys. Acta, 445:632–644, 1976a.
Gupta, SK, and Rothstein, M: Triosephosphate isomerase from young and old Turbatrix aceti. Arch. Biochem. Biophys., 174: 333–338, 1976b.
Harman D: The aging process. Proc. Natl. Acad. Sci. USA, 78:7124–7128, 1981.
Hartman, PS, and Herman, RK: Radiation-sensitive mutants of Caenorhabditis elegans. Genetics, 102: 159–178, 1982.
Hekimi, S, Lakowski, B, Barnes, TM, and Ewbank, JJ: Molecular genetics of life span in C. elegans: how much does it tell us? Trends Genet., 14:14–20, 1998.
Hodgkin, J, and Doniah, T: Natural variation and copulatory plug formation in Caenorhabditis elegans. Genetics, 146: 149–164, 1997.
Honda, Y, and Honda, S: The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J., 13: 1385–1393, 1999.
Hosokawa, H, Ishii, N, Ishida, H, Ichimori, K, Nakazawa, H, and Suzuki, K: Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech. Ageing Devel., 74:161–170, 1994.
Hosono, R, Nishimoto, S, and Kuno, S: Alterations of life span in the nematode Caenorhabditis elegans under monoxenic culture conditions. Exp. Gerontol., 24: 251–264, 1989.
Hsin, H, and Kenyon, C: Signals from the reproductive system regulate the lifespan of C. elegans. Nature, 399:362–366, 1999.
Hunter, T, Bannister, WH, and Hunter, GJ: Cloning, expression and characterization of two manganese superoxide dismutases from Caenorhabditis elegans. J. Biol. Chem., 272:28652–28659, 1997.
Ishii, N, Fujii, M, Hartman, PS, Tsuda, M, Yasuda, K, Senoo-Matsuda, N, Yanase, S, Ayusawa, D, and Suzuki, K. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature, 394:694–697, 1998.
Ishii, N, Suzuki, N, Hartman, P, and Suzuki, K: 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, 1993.
Ishii, N, Suzuki, N, Hartman, PS, and Suzuki, K: The effects of temperature on the longevity of a radiation-sensitive mutant rad-8 of the nematode Caenorhabditis elegans. J. Gerontol., 49:B117–B120, 1994.
Ishii, N, Takahashi, K, Tomita, S, Keino, T, Honda, S, Yoshino, K, and Suzuki, K. A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mut. Res., 237:165–71, 1990.
Jazwinski, SM: Longevity, genes and aging. Science, 273:54–59, 1996.
Jazwinski, SM: Molecular mechanisms of yeast longevity. Trends Microbiol., 7: 247–252, 1999.
Johnson, TE, and McCaffrey, G: Programmed aging or error catastrophe? An examination by two-dimensional polyacrylamide gel electrophoresis. Mech. Ageing Dev., 30: 285–297, 1985.
Jonassen, T, Proft, M, Randez-Gil, F, Schultz, JR, Marbois, BN, Entian, K-D, and Clarke, CF: Yeast CLK-1 homologue (COQ7/CAT5) is a mitochondrial protein in coenzyme Q synthesis. J. Biol. Chem., 273: 3351–3357, 1998.
Kenyon, C, Chang, J, Gensch, E, Rudner, A, and Tabtiang, RA: C. elegans mutant that lives twice as long as wild type. Nature, 366:461–464, 1993.
Kimura, K, Tissenbaum, HA, Liu, Y, and Ruvkun, G: daf-2, an insulin receptor family member that regulates longevity and diapause in Caenorhabditis elegans. Science, 277:942–946, 1997.
Kirkwood, TBL, and Rose, MR: Evolution of senescence: late survival sacrificed for reproduction. Phil. Trans. R. Soc. Lond. B, 332: 15–24, 1991.
Klass, MR: Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev., 6: 413–429, 1977.
Klass, MR, and Hirsh, D: Nonaging developmental variant of Caenorhabditis elegans. Nature, 260: 523–525, 1976.
Lakowski, B, and Hekimi, S: Determination of life span in Caenorhabditis elegans by four clock genes. Science, 272:1010–1013, 1996.
Lakowski, B, and Hekimi, S: The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 95:13091–13096, 1998.
Larsen, PL: Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 90:8905–8909, 1993.
Larsen, PL, Albert, PS, and Riddle, DL: Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics, 139:1567–1583, 1995.
Lee, C-K, Klopp, RC, Weindruch, R, and Prolla, TA: Gene expression profile of aging and its retardation by caloric restriction. Science, 285: 1390–1393, 1999.
Lin, K, Dorman, JB, Rodan, A, and Kenyon, C: daf-16: An HFN-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science, 278: 1319–1322, 1997.
Lin, Y-J, Seroude, L, and Benzer, S: Extended life-span and stress resistance in the Drosophila mutant methuselah. Science, 282: 943–946, 1998.
Liochev, SI, and Fridovich, I: Lucigenin (bis-N-methylacridinium) as a mediator of superoxide anion production. Arch. Biochem. Biophys., 337:115–120, 1997.
Lithgow, GJ: Invertebrate gerontology: the age mutations of Caenorhabditis elegans. BioEssays, 18: 809–815, 1996.
Lithgow, GJ, White, TM, Hinerfeld, DA, and Johnson, TE: Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J. Gerontol., 49:B270–B276, 1994.
Lithgow, GJ, White, TM, Melov, S, and Johnson, TE: Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. USA, 92:7540–7544, 1995.
Liu, A, and Rothstein, M: Nematode biochemistry XV. Enzyme changes related to glycerol excretion in Caenorhabditis briggsae. Comp. Biochem. Physiol., 54B:233–238, 1976.
Liu, F, Thatcher, JD, Barra, JM, and Epstein, HF: Bifunctional glyoxylate cycle protein of Caenorhabditis elegans: a developmentally regulated protein of intestine and muscle. Dev. Biol., 169:399–414, 1995.
Marbois, BN, and Clarke, CF: The COQ7 gene encodes a protein in Saccharomyces cerevisiae necessary for ubiquinone biosynthesis. J. Biol. Chem., 271:2995–3004, 1996.
Masoro, EJ: Food restriction in rodents: an evaluation of its role in the study of aging. J. Gerontol. Biol. Sci., 43: B59–B64, 1988.
Masoro, EJ: Dietary restriction. Exp. Gerontol., 30:291–298, 1995.
Mihaylova, VT, Borland, CZ, Manjarrez, L, Stern, MJ, and Sun, H: The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc. Natl. Acad. Sci. USA 96: 7427–7432, 1999.
Morris, JZ, Tissenbaum, HA, and Ruvkun, G: A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature, 382:536–539, 1996.
Murakami, S, and Johnson, TE: A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics, 143:1207–1218, 1996.
Murakami, S, and Johnson, TE: Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene. Curr. Biol., 8:1091–1094, 1998.
O’Riordan, V, and Burnell, AM: Intermediary metabolism in the dauer larva of the nematode Caenorhabditis elegans. I. Glycolysis, gluconeogenesis, oxidative phosphorylation and the tricaboxylic acid cycle. Comp. Biochem. Physiol., 92B:233–238, 1989.
O’Riordan, V, and Burnell, AM: Intermediary metabolism in the dauer larva of the nematode Caenorhabditis elegans. II. The glyoxylate cycle and fatty acid oxidation. Comp. Biochem. Physiol., 95B:125–130, 1990.
Ogg, S, Paradis, S, Gottlieb, S, Patterson, GI, Lee, L, Tissenbaum, HA, and Ruvkun, G: The Fork Head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature, 389: 994–999, 1997.
Ogg, S, and Ruvkun, G: The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic pathway. Mol. Cell, 2:887–893, 1998.
Orgel, LE: The maintenance of the accuracy of protein synthesis and its relevance to aging. Proc. Natl. Acad. Sci. USA, 49: 517–521, 1963.
Orr, WC, and Sohal, RC: Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263: 1128–1130, 1994.
Paradis, S, Ailion, M, Toker, A, Thomas, J, and Ruvkun, G: A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev., 13: 1438–1452, 1999.
Paradis, S, and Ruvkun, G: Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev., 12:2488–2489, 1998.
Parkes, TL, Elia, AJ, Dickinson, D, Hilliker, AJ, Phillips, JP, and Boulianne, GL: Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat. Genet., 19: 171–174, 1998.
Pearl, R: The Rate of Living. University of London Press, London, 1928.
Prasanna, HR, and Lane, RS: Protein degradation in aged nematodes (Turbatrix aceti). Biochem. Biophys. Res. Commun., 86: 552–559, 1979.
Proft, M, Kötter, P, Hedges, D, Bojunga, N, and Entian, K-D: CAT5, a new gene necessary for derepression of gluconeogenetic enzymes in Saccharomyces cerevisiae. EMBO J., 14:6116–6126, 1995.
Reiss, U, and Rothstein, M: Age related changes in isocitrate lyase from the free-living nematode, Turbatrix aceti. J. Biol. Chem., 250: 826–830, 1975.
Reznick, AZ, and Gershon, D: Age related alterations in purified fructose-1-6-diphosphate aldolase in the nematode Turbatrix aceti. Mech. Ageing Dev., 6: 345–353, 1977.
Riddle, DL, Blumenthal, T, Meyer, BJ, and Priess, JR: C. elegans II. Plainview, New York: Cold Spring Harbor Laboratory press, 1997.
Riddle, DL: The dauer larva, in The nematode Caenorhabditis elegans, edited by Wood, WB, Plainview, New York, Cold Spring Harbor Laboratory Press, 1988, pp. 393–412.
Riddle, DL, and Albert, PS: Genetic and environmental regulation of dauer larva development, in C. elegans II, edited by Riddle, DL, Blumenthal, T, Meyer, BJ, and Priess, JR, Plainview, New York, Cold Spring Harbor Laboratory Press, 1997, pp. 739–768.
Riha, VF, and Luckinbill, LS: Selection for longevity favours stringent metabolic control in Drosophila melanogaster. J. Gerontol. Biol. Sci., 51: B284–B294, 1996.
Rouault, J-P, Kuwabara, PE, Sinilnikova, OM, Duret, L, Thierry-Mieg, D, and Billaud, M: Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Curr. Biol., 9: 329–332, 1999.
Rothstein, M: Biochemical approaches to aging. New York, Academic Press, 1982, pp. 198–255.
Rothstein, M: Effects of aging on enzymes, in Nematodes as biological models, Vol. 2, Aging and other model systems, edited by Zuckerman, BM, New York, Academic Press, 1980, pp. 29–46.
Rothstein, M, and Sharma, HK: Altered enzymes in the free-living nematode, Turbatrix aceti, aged in the absence of fluorodeoxyuridine. Mech. Aging Dev., 8: 175–180, 1978.
Rubner, M: Das problem der Lebensdauer und seine Beziehungen zum Wachstum und Ernährung. Munich: Oldenbourg, 1908.
Sarkis, GJ, Ashcom, JD, Hawdon, JM, and Jacobson, LA: Decline in protease activities with age in the nematode Caenorhabditis elegans. Mech. Ageing Dev., 45: 191–201, 1988.
Sharma, HK, Gupta, SK, and Rothstein, M: Age-related alteration of enolase in the free-living nematode Turbatrix aceti. Arch. Biochem. Biophys., 174: 324–332, 1976.
Sharma, HK, and Rothstein, M: Age-realted changes in the properties of enolase from Turbatrix aceti. Biochemistry, 17: 2869–2876, 1978a.
Sharma, HK, and Rothstein, M: Serological evidence for the alteration of enolase during aging. Mech. Ageing Dev., 8: 341–354, 1978b.
Sharma, HK, and Rohtstein, M: Altered enolase in Turbatrix aceti results from conformational changes in the enzyme. Proc. Natl. Acad. Sci USA, 77: 5865–5868, 1980.
Sohal, RS: The rate of living theory: A contemporary interpretation, in Insect aging: Strategies and mechanisms, edited by Collatz, KG, and Sohal, RS, Berlin: Springer-Verlag, 1986, pp. 23–44.
Sulston, J, and Hodgkin, J: Methods, in The nematode Caenorhabditis elegans, edited by Wood, WB, Plainview, New York, Cold Spring Harbor Laboratory Press, 1988, pp. 587–606.
Sun, J, Kale, SP, Childress, AM, Pinswasdi, C, and Jazwinski, SM: Divergent roles of RAS1 and RAS2 in yeast longevity. J. Biol. Chem., 269: 18638–18645, 1994.
Suzuki, N, Inokura, K, Yasuda, K, and Ishii, N: Cloning, sequencing and mapping of a manganese superoxide dismutase gene of the nematode Caenorhabditis elegans. DNA Res., 4: 171–174, 1996.
Taub, J, Lau, JF, Ma, C, Hahn, JH, Hoque, R, Rothblatt, J, and Chalfie, M: A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature, 399:162–166, 1999.
Tawe, WN, Eschbach, M-L, Walter, RD, and Henkle-Dührsen, K: Identification of stress-responsive genes in Caenorhabditis elegans using RT-PCR differential display. Nucl. Acids Res., 26: 1621–1627, 1998.
The C. elegans Sequencing Consortium: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science, 282:2012–2018, 1998.
Tissenbaum, HA, and Ruvkun, G: An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics, 148:703–717, 1998.
Vanfleteren, JR: Oxidative stress and ageing in Caenorhabditis elegans. Biochem. J., 292:605–608, 1993.
Vanfleteren, JR, Braeckman, BP, Roelens, I, and De Vreese, A: Age-specific modulation of light production potential, and alkaline phosphatase and protein tyrosine kinase activities in various age mutants of Caenorhabditis elegans. J. Gerontol. Biol. Sci., 53:B380–B390, 1998a.
Vanfleteren, JR, and De Vreese, A: Analysis of the proteins of aging Caenorhabditis elegans by high resolution two-dimensional gel electrophoresis. Electrophoresis, 15: 289–296, 1994.
Vanfleteren, JR, and De Vreese, A. Rate of aerobic metabolism and superoxide production rate potential in the nematode Caenorhabditis elegans. J. Exp. Zool., 274:93–100, 1996.
Vanfleteren, JR, and De Vreese, A: The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J., 9:1355–1361, 1995.
Vanfleteren, JR, and De Vreese, A: Modulation of kinase activities in dauers and long-lived mutants of Caenorhabditis elegans. J. Gerontol., 52:B212–B216, 1997.
Vanfleteren, JR, De Vreese, A, and Braeckman, BP: Two-parameter logistic and Weibull equations provide better fits to survival data from isogenic populations of Caenorhabditis elegans in axenic culture than does the Gompertz model. J. Gerontol. Biol. Sci., 53: B393–B403, 1998b.
Van Remmen, H, Ward, WF, Sabia, RV, and Richardson, A: Effect of age on gene expression and protein degradation, in Handbook of physiology. Section 11: Aging, edited by Masoro, EJ, New York: Oxford University Press, 1995, pp. 171–234.
Van Voorhies, WA, and Ward, S: Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc. Natl. Acad. Sci. USA, 96: 11399–11403, 1999.
Voet, D, and Voet, H: Biochemistry. New York, John Wiley and Sons, 1990, p. 540.
Wadsworth, WG, and Riddle, DL: Developmental regulation of energy metabolism in Caenorhabidtis elegans. Dev. Biol., 132: 167–173, 1989.
Wong, A, Boutis, P, and Hekimi, S: Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics, 139: 1247–1259, 1995.
Wood, WB: The Nematode Caenorhabditis elegans. Plainview, New York: Cold Spring Harbor Laboratory, 1988.
Yasuda, K, Adachi, H, Fujiwara, Y, and Ishii, N: Protein carbonyl accumulation in aging dauer formation-defective (daf) mutants of Caenorhabditis elegans. J. Gerontol. Biol. Sci., 54: B47–B51, 1999.
Yeargers, E: Effect of gamma-radiation on dauer larvae of Caenorhabditis elegans. J. Nematol., 13: 235–237, 1981.
Yeh, WH: Genes acting late in the signaling pathway for Caenorhabditis elegans dauer larval development. Ph. D. thesis, University of Missouri, Columbia, 1991.
Zuckerman, BM, and Himmelhoch, S: Nematodes as models to study aging, in Nematodes as biological models. II Aging and other model systems, edited by Zuckerman, BM, New York, Academic Press, 1980, pp. 3–28.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Braeckman, B.P., Houthoofd, K. & Vanfleteren, J.R. Patterns of metabolic activity during aging of the wild type and longevity mutants of Caenorhabditis elegans . AGE 23, 55–73 (2000). https://doi.org/10.1007/s11357-000-0007-8
Issue Date:
DOI: https://doi.org/10.1007/s11357-000-0007-8