The genetics of caloric restriction in Caenorhabditis elegans

October 27, 1998
95 (22) 13091-13096

Abstract

Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans. Mutations in many genes (eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C. elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (age-1, daf-2, daf-16, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1). We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.

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Acknowledgments

We thank T. Barnes for lengthy discussions, C. Bénard and B. McCreight for carefully reading the manuscript, and D. Raizen, L. Avery, and J. Hodgkin for strains. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources. This work was supported by a grant to S.H. from the Medical Research Council of Canada and by a fellowship to B.L. from the Fonds pour la Formation de Chercheurs et l’Aide à la Recherche (FCAR), Québec.

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 95 | No. 22
October 27, 1998
PubMed: 9789046

Classifications

Submission history

Received: May 29, 1998
Accepted: September 3, 1998
Published online: October 27, 1998
Published in issue: October 27, 1998

Acknowledgments

We thank T. Barnes for lengthy discussions, C. Bénard and B. McCreight for carefully reading the manuscript, and D. Raizen, L. Avery, and J. Hodgkin for strains. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources. This work was supported by a grant to S.H. from the Medical Research Council of Canada and by a fellowship to B.L. from the Fonds pour la Formation de Chercheurs et l’Aide à la Recherche (FCAR), Québec.

Authors

Affiliations

Bernard Lakowski*
Department of Biology, McGill University, 1205 Dr. Penfield Avenue, Montréal, Québec, Canada H3A 1B1
Siegfried Hekimi
Department of Biology, McGill University, 1205 Dr. Penfield Avenue, Montréal, Québec, Canada H3A 1B1

Notes

*
Present address: Genzentrum, Ludwig-Maximilians Universität, Feodor-Lynen Strasse 25, D-81377, Munich, Germany.
To whom reprint requests should be addressed. e-mail: [email protected].
Communicated by William B. Wood III, University of Colorado, Boulder, CO

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    The genetics of caloric restriction in Caenorhabditis elegans
    Proceedings of the National Academy of Sciences
    • Vol. 95
    • No. 22
    • pp. 12737-13348

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