Journal of the American Aging Association

, Volume 23, Issue 2, pp 55–73 | Cite as

Patterns of metabolic activity during aging of the wild type and longevity mutants of Caenorhabditis elegans

  • Bart P. Braeckman
  • K. Houthoofd
  • Jacques R. Vanfleteren


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.


Reactive Oxygen Species Life Span Dietary Restriction Caenorhabditis Elegans Shorten Life Span 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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.Google Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. Anderson, GL: Responses of dauer larvae of Caenorhabditis elegans (Nematoda: Rhabditidae) to thermal stress and oxygen deprivation. Can. J. Zool., 56: 1786–1791, 1978.Google Scholar
  4. Anderson, GL: Superoxide dismutase activity in the dauer larvae of Caenorhabditis elegans. Can. J. Zool., 60:288–291, 1982.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. Arking, R: Biology of aging: Observations and principles. Sunderland, Massachusetts, Sinauer Associates, 1998.Google Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. Brown-Borg, HM, Borg, KE, Meliska, CJ, and Bartke, A: Dwarf mice and the ageing process. Nature, 384: 33, 1996.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. De Cuyper, C, and Vanfleteren, JR: Oxygen consumption during development and aging of the nematode Caenorhabditis elegans. Comp. Biochem. Physiol., 73A: 283–289, 1982.CrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.Google Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. Fabian, TE, and Johnson, TE: Production of age-synchronous mass cultures of Caenorhabditis elegans. J. Gerontol. Biol. Sci., 49: B145–B156, 1994.Google Scholar
  17. Faulkner, K, and Fridovich, I: Luminol and Lucigenin as detectors for O2 . Free Rad. Biol. Med., 15: 447–451, 1993.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.Google Scholar
  20. Finch, C: Longevity, Senescence, and the Genome. Chicago, The University of Chicago Press, 1990, pp. 281–282.Google Scholar
  21. 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.Google Scholar
  22. 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.Google Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. Guarente, L, Ruvkun, G, and Amasino, R: Aging, life span, and senescence. Proc. Natl. Acad. Sci. USA, 95: 11034–11036, 1998.Google Scholar
  31. Gupta, SK, and Rothstein, M: Phosphoglycerate kinase from young and old Turbatrix aceti. Biochim. Biophys. Acta, 445:632–644, 1976a.PubMedGoogle Scholar
  32. Gupta, SK, and Rothstein, M: Triosephosphate isomerase from young and old Turbatrix aceti. Arch. Biochem. Biophys., 174: 333–338, 1976b.PubMedCrossRefGoogle Scholar
  33. Harman D: The aging process. Proc. Natl. Acad. Sci. USA, 78:7124–7128, 1981.PubMedGoogle Scholar
  34. Hartman, PS, and Herman, RK: Radiation-sensitive mutants of Caenorhabditis elegans. Genetics, 102: 159–178, 1982.PubMedGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. Hodgkin, J, and Doniah, T: Natural variation and copulatory plug formation in Caenorhabditis elegans. Genetics, 146: 149–164, 1997.PubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. Hsin, H, and Kenyon, C: Signals from the reproductive system regulate the lifespan of C. elegans. Nature, 399:362–366, 1999.PubMedCrossRefGoogle Scholar
  41. 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.Google Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.Google Scholar
  46. Jazwinski, SM: Longevity, genes and aging. Science, 273:54–59, 1996.PubMedGoogle Scholar
  47. Jazwinski, SM: Molecular mechanisms of yeast longevity. Trends Microbiol., 7: 247–252, 1999.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. Kirkwood, TBL, and Rose, MR: Evolution of senescence: late survival sacrificed for reproduction. Phil. Trans. R. Soc. Lond. B, 332: 15–24, 1991.Google Scholar
  53. Klass, MR: Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev., 6: 413–429, 1977.PubMedCrossRefGoogle Scholar
  54. Klass, MR, and Hirsh, D: Nonaging developmental variant of Caenorhabditis elegans. Nature, 260: 523–525, 1976.PubMedCrossRefGoogle Scholar
  55. Lakowski, B, and Hekimi, S: Determination of life span in Caenorhabditis elegans by four clock genes. Science, 272:1010–1013, 1996.PubMedGoogle Scholar
  56. Lakowski, B, and Hekimi, S: The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 95:13091–13096, 1998.Google Scholar
  57. Larsen, PL: Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 90:8905–8909, 1993.PubMedGoogle Scholar
  58. Larsen, PL, Albert, PS, and Riddle, DL: Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics, 139:1567–1583, 1995.PubMedGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 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.PubMedCrossRefGoogle Scholar
  61. Lin, Y-J, Seroude, L, and Benzer, S: Extended life-span and stress resistance in the Drosophila mutant methuselah. Science, 282: 943–946, 1998.PubMedCrossRefGoogle Scholar
  62. Liochev, SI, and Fridovich, I: Lucigenin (bis-N-methylacridinium) as a mediator of superoxide anion production. Arch. Biochem. Biophys., 337:115–120, 1997.PubMedCrossRefGoogle Scholar
  63. Lithgow, GJ: Invertebrate gerontology: the age mutations of Caenorhabditis elegans. BioEssays, 18: 809–815, 1996.PubMedCrossRefGoogle Scholar
  64. Lithgow, GJ, White, TM, Hinerfeld, DA, and Johnson, TE: Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J. Gerontol., 49:B270–B276, 1994.PubMedGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. Liu, A, and Rothstein, M: Nematode biochemistry XV. Enzyme changes related to glycerol excretion in Caenorhabditis briggsae. Comp. Biochem. Physiol., 54B:233–238, 1976.Google Scholar
  67. 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.PubMedCrossRefGoogle Scholar
  68. 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.PubMedCrossRefGoogle Scholar
  69. Masoro, EJ: Food restriction in rodents: an evaluation of its role in the study of aging. J. Gerontol. Biol. Sci., 43: B59–B64, 1988.Google Scholar
  70. Masoro, EJ: Dietary restriction. Exp. Gerontol., 30:291–298, 1995.PubMedCrossRefGoogle Scholar
  71. 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.PubMedCrossRefGoogle Scholar
  72. 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.PubMedCrossRefGoogle Scholar
  73. Murakami, S, and Johnson, TE: A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics, 143:1207–1218, 1996.PubMedGoogle Scholar
  74. 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.PubMedCrossRefGoogle Scholar
  75. 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.Google Scholar
  76. 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.Google Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. 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.PubMedCrossRefGoogle Scholar
  79. Orgel, LE: The maintenance of the accuracy of protein synthesis and its relevance to aging. Proc. Natl. Acad. Sci. USA, 49: 517–521, 1963.PubMedGoogle Scholar
  80. Orr, WC, and Sohal, RC: Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263: 1128–1130, 1994.PubMedGoogle Scholar
  81. 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.PubMedGoogle Scholar
  82. 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.PubMedGoogle Scholar
  83. 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.PubMedCrossRefGoogle Scholar
  84. Pearl, R: The Rate of Living. University of London Press, London, 1928.Google Scholar
  85. Prasanna, HR, and Lane, RS: Protein degradation in aged nematodes (Turbatrix aceti). Biochem. Biophys. Res. Commun., 86: 552–559, 1979.PubMedCrossRefGoogle Scholar
  86. 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.PubMedGoogle Scholar
  87. 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.PubMedGoogle Scholar
  88. 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.PubMedCrossRefGoogle Scholar
  89. Riddle, DL, Blumenthal, T, Meyer, BJ, and Priess, JR: C. elegans II. Plainview, New York: Cold Spring Harbor Laboratory press, 1997.Google Scholar
  90. 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.Google Scholar
  91. 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.Google Scholar
  92. Riha, VF, and Luckinbill, LS: Selection for longevity favours stringent metabolic control in Drosophila melanogaster. J. Gerontol. Biol. Sci., 51: B284–B294, 1996.Google Scholar
  93. 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.PubMedCrossRefGoogle Scholar
  94. Rothstein, M: Biochemical approaches to aging. New York, Academic Press, 1982, pp. 198–255.Google Scholar
  95. 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.Google Scholar
  96. 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.PubMedCrossRefGoogle Scholar
  97. Rubner, M: Das problem der Lebensdauer und seine Beziehungen zum Wachstum und Ernährung. Munich: Oldenbourg, 1908.Google Scholar
  98. 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.PubMedCrossRefGoogle Scholar
  99. 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.PubMedCrossRefGoogle Scholar
  100. Sharma, HK, and Rothstein, M: Age-realted changes in the properties of enolase from Turbatrix aceti. Biochemistry, 17: 2869–2876, 1978a.PubMedCrossRefGoogle Scholar
  101. Sharma, HK, and Rothstein, M: Serological evidence for the alteration of enolase during aging. Mech. Ageing Dev., 8: 341–354, 1978b.PubMedCrossRefGoogle Scholar
  102. 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.PubMedGoogle Scholar
  103. 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.Google Scholar
  104. 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.Google Scholar
  105. 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.Google Scholar
  106. 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.CrossRefGoogle Scholar
  107. 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.PubMedCrossRefGoogle Scholar
  108. 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.PubMedCrossRefGoogle Scholar
  109. The C. elegans Sequencing Consortium: Genome sequence of the nematode C. elegans: a platform for investigating biology. Science, 282:2012–2018, 1998.Google Scholar
  110. Tissenbaum, HA, and Ruvkun, G: An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics, 148:703–717, 1998.PubMedGoogle Scholar
  111. Vanfleteren, JR: Oxidative stress and ageing in Caenorhabditis elegans. Biochem. J., 292:605–608, 1993.PubMedGoogle Scholar
  112. 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.Google Scholar
  113. 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.PubMedCrossRefGoogle Scholar
  114. 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.PubMedCrossRefGoogle Scholar
  115. 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.PubMedGoogle Scholar
  116. 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.Google Scholar
  117. 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.Google Scholar
  118. 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.Google Scholar
  119. 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.Google Scholar
  120. Voet, D, and Voet, H: Biochemistry. New York, John Wiley and Sons, 1990, p. 540.Google Scholar
  121. Wadsworth, WG, and Riddle, DL: Developmental regulation of energy metabolism in Caenorhabidtis elegans. Dev. Biol., 132: 167–173, 1989.PubMedCrossRefGoogle Scholar
  122. 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.PubMedGoogle Scholar
  123. Wood, WB: The Nematode Caenorhabditis elegans. Plainview, New York: Cold Spring Harbor Laboratory, 1988.Google Scholar
  124. 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.Google Scholar
  125. Yeargers, E: Effect of gamma-radiation on dauer larvae of Caenorhabditis elegans. J. Nematol., 13: 235–237, 1981.Google Scholar
  126. Yeh, WH: Genes acting late in the signaling pathway for Caenorhabditis elegans dauer larval development. Ph. D. thesis, University of Missouri, Columbia, 1991.Google Scholar
  127. 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.Google Scholar

Copyright information

© American Aging Association, Inc. 2000

Authors and Affiliations

  • Bart P. Braeckman
    • 1
  • K. Houthoofd
    • 1
  • Jacques R. Vanfleteren
    • 1
  1. 1.Department of BiologyUniversity of GentGentBelgium

Personalised recommendations