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A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants

Nature volume 399, pages 162–166 (1999)Cite this article

A Retraction to this article was published on 13 February 2003

Abstract

The dauer larva is an alternative larval stage in Caenorhabditis elegans which allows animals to survive through periods of low food availability. Well-fed worms live for about three weeks, but dauer larvae can live for at least two months without affecting post-dauer lifespan1. Mutations in daf-2 and age-1, which produce a dauer constitutive (Daf-C) phenotype, and in clk-1, which are believed to slow metabolism, markedly increase adult lifespan2. Here we show that a ctl-1 mutation reduces adult lifespan in otherwise wild-type animals and eliminates the daf-c and clk-1 -mediated extension of adult lifespan. ctl-1 encodes an unusual cytosolic catalase; a second gene, ctl-2, encodes a peroxisomal catalase. ctl-1 messenger RNA is increased in dauer larvae and adults with the daf-c mutations. We suggest that the ctl-1 catalase is needed during periods of starvation, as in the dauer larva, and that its misexpression in daf-c and clk-1 adults extends lifespan. Cytosolic catalase may have evolved to protect nematodes from oxidative damage produced during prolonged dormancy before reproductive maturity, or it may represent a general mechanism for permitting organisms to cope with the metabolic changes that accompany starvation.

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Figure 1: Catalase expression in wild-type and mutant animals.
Figure 2
Figure 3: Effect of ctl-1 activity on lifespan.
Figure 4: Autofluorescent material accumulates as animals age.

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References

  1. Riddle, D. L. & Alberts, P. S. in C. elegans II (eds Riddle, D. L., Blumenthal T., Meyer, B. J. & Priess, J. R.) 739–768 (Cold Spring Harbor Press, New York, (1997).

    Google Scholar 

  2. Kenyon, C. in C. elegans II (eds Riddle, D. L., Blumenthal, T., Meyer, B. J. & Priess, J. R.) 791–814 (Cold Spring Harbor Press, New York, (1997).

    Google Scholar 

  3. Vanfleteren, J. R. Oxidative stress and ageing in Caenorhabditis elegans. Biochem. J. 292, 605–608 (1993).

    Article  CAS  Google Scholar 

  4. Waterston, R. et al. Asurvey of expressed genes in Caenorhabditis elegans. Nature Genet. 1, 114–123 (1992).

    Article  CAS  Google Scholar 

  5. Gould, S. J., Keller, G.-A., Hosken, N., Wilkinson, J. & Subramani, S. Aconserved tripeptide sorts proteins to peroxisomes. J. Cell Biol. 108, 1657–1664 (1989).

    Article  CAS  Google Scholar 

  6. Hosokawa, H. et al. Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech. Ageing Dev. 74, 161–170 (1994).

    Article  CAS  Google Scholar 

  7. Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    Article  CAS  Google Scholar 

  8. Morris, J. Z., Tissenbaum, H. A. & Ruvkun, G. Aphosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382, 536–539 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Ogg, S. et al. The Forkhead transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994–999 (1997).

    Article  ADS  CAS  Google Scholar 

  10. Lin, K., Dorman, J. B., Rodan, A. & Kenyon, C. daf-16 : An HNF-3/forkhead family member than can function to double the life-span of Caenorhabditis elegans. Science 278, 1319–1322 (1997).

    Article  ADS  CAS  Google Scholar 

  11. Larsen, P., Albert, P. S. & Riddle, D. L. Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139, 1567–1583 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ewbank, J. J. et al. Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275, 980–983 (1997).

    Article  CAS  Google Scholar 

  13. Beckman, K. B. & Ames, B. N. The free radical theory of aging matures. Physiol. Rev. 78, 547–581 (1998).

    Article  CAS  Google Scholar 

  14. Orr, W. C. & Sohal, R. S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263, 1128–1130 (1994).

    Article  ADS  CAS  Google Scholar 

  15. Amstad, P. et al. The balance between Cu, Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry 30, 9305–9313 (1991).

    Article  CAS  Google Scholar 

  16. Parkes, T. L. et al. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nature Genet. 10, 171–175 (1998).

    Article  Google Scholar 

  17. Kirkwood, T. B. L. & Rose, M. R. Evolution of senescence: late survival sacrificed for reproduction. Phil. Trans. R. Soc. Lond. B 332, 15–24 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Ruis, H. & Koller, F. in Oxidative Stress and the Molecular Biology of Antioxidant Defenses (ed. Scandalios, J. G.) 309–342 (Cold Spring Harbor Press, New York, (1997).

    Google Scholar 

  19. Scandalios, J. G., Guan, L. & Polidoros, A. N. in Oxidative Stress and the Molecular Biology of Antioxidant Defenses (ed. Scandalios, J. G.) 343–406 (Cold Spring Harbor Press, New York, (1997).

    Google Scholar 

  20. Roels, F. Cytochemical demonstration of extraperoxisomal catalase. I. Sheep liver. J.. Histochem. Cytochem. 24, 713–724 (1976).

    Article  CAS  Google Scholar 

  21. Roels, F., de Coster, W. & Goldfischer, S. Cytochemical demonstration of extraperoxisomal catalase. II. Liver of rhesus monkey and guinea pig. J. Histochem. Cytochem. 25, 157–160 (1977).

    Article  CAS  Google Scholar 

  22. Yamamoto, K., Volkl, A., Hashimoto, T. & Fahimi, H. D. Catalase in guinea pig hepatocytes is localized in cytoplasm, nuclear matrix and peroxisomes. Eur. J. Cell Biol. 46, 129–135 (1988).

    CAS  PubMed  Google Scholar 

  23. Bulitta, C., Ganea, C., Fahimi, H. D. & Volkl, A. Cytoplasmic and peroxisomal catalases of the guinea pig liver: evidence for two distinct proteins. Biochim. Biophys. Acta 1293, 55–62 (1996).

    Article  Google Scholar 

  24. Bissinger, P. H., Wieser, R., Hamilton, B. & Ruis, H. Control of Saccharomyces cerevisiae catalase T gene (CTT1) expression by nutrient supply via the RAS-cyclic AMP pathway. Mol. Cell Biol. 9, 1309–1315 (1989).

    Article  CAS  Google Scholar 

  25. Loewen, P. in Oxidative Stress and the Molecular Biology of Antioxidant Defenses (ed. Scandalios, J. G.) 273–308 (Cold Spring Harbor Press, New York, (1997).

    Google Scholar 

  26. Masoro, E. J., Shimokawa, I. & Yu, B. P. Retardation of the aging processes in rats by food restriction. Ann. N^Y Acad. Sci. 621, 337–352 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Sulston, J. & Hodgkin, J. in The Nematode Caenorhabditis elegans (ed. Wood, W. B.) 587–606 (Cold Spring Harbor Press, New York, (1988).

    Google Scholar 

  28. Peters, T. J., Muller, M. & DeDuve, C. Lysosomes of the arterial wall. I. Isolation and subcellular fractionation of cells from normal rabbit aorta. J. Exp. Med. 136, 1117–1139 (1972).

    Article  CAS  Google Scholar 

  29. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory Press, New York, (1989).

    Google Scholar 

  30. Mello, C. & Fire, A. Methods Cell Biol. 48, 451–482 (1995).

    Google Scholar 

Download references

Acknowledgements

This work was supported by the NIH (M.C. and J.R.) and by the American Cancer Society (J.R.). Some strains were received from the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources.

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Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, 10027, New York, USA

    James Taub, Joe F. Lau, Charles Ma, Jang Hee Hahn, Rafaz Hoque, Jonathan Rothblatt & Martin Chalfie

  2. Department of Biological Sciences, 6044 Gilman Laboratory, Dartmouth College, Hanover, 03755, New Hampshire, USA

    James Taub & Jonathan Rothblatt

  3. Department of Anatomy, College of Medicine, Kangwon National University, 200-701, Chunchon, Korea

    Jang Hee Hahn

  4. Center for Applied Genomics, Hoechst Marion Roussel, Fraunhoferstr., 82152 22, Martinsried, Germany

    Jang Hee Hahn

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Correspondence to Martin Chalfie.

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Taub, J., Lau, J., Ma, C. et al. A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature 399, 162–166 (1999). https://doi.org/10.1038/20208

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