Genes that Regulate Both Development and Longevity in Caenorhabditis elegans

INVESTIGATIONS

Genes that Regulate Both Development and Longevity in Caenorhabditis elegans

P. L. Larsen, P. S. Albert and D. L. Riddle
Present address: Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089.

The nematode Caenorhabditis elegans responds to conditions of overcrowing and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determination of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan.

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				C. Shen, D. Nettleton, M. Jiang, S. K. Kim, and J. A. Powell-Coffman Roles of the HIF-1 Hypoxia-inducible Factor during Hypoxia Response in Caenorhabditis elegans J. Biol. Chem., May 27, 2005; 280(21): 20580 - 20588. [Abstract] [Full Text] [PDF]

				J. Halaschek-Wiener, J. S. Khattra, S. McKay, A. Pouzyrev, J. M. Stott, G. S. Yang, R. A. Holt, S. J.M. Jones, M. A. Marra, A. R. Brooks-Wilson, et al. Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression Genome Res., May 1, 2005; 15(5): 603 - 615. [Abstract] [Full Text] [PDF]

				Y. Shostak and K. R. Yamamoto Overlapping but Separable Determinants of DNA Binding and Nuclear Localization Map to the C-terminal End of the Caenorhabditis elegans DAF-12 DNA Binding Domain J. Biol. Chem., February 25, 2005; 280(8): 6554 - 6560. [Abstract] [Full Text] [PDF]

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				W. Ao, J. Gaudet, W. J. Kent, S. Muttumu, and S. E. Mango Environmentally Induced Foregut Remodeling by PHA-4/FoxA and DAF-12/NHR Science, September 17, 2004; 305(5691): 1743 - 1746. [Abstract] [Full Text] [PDF]

				A. H. Ludewig, C. Kober-Eisermann, C. Weitzel, A. Bethke, K. Neubert, B. Gerisch, H. Hutter, and A. Antebi A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging Genes & Dev., September 1, 2004; 18(17): 2120 - 2133. [Abstract] [Full Text] [PDF]

				K. Jia, D. Chen, and D. L. Riddle The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span Development, August 15, 2004; 131(16): 3897 - 3906. [Abstract] [Full Text] [PDF]

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				N. Arantes-Oliveira, J. R. Berman, and C. Kenyon Healthy Animals with Extreme Longevity Science, October 24, 2003; 302(5645): 611 - 611. [Full Text] [PDF]

				S. Kim Molecular Biology of Aging Arch Surg, October 1, 2003; 138(10): 1051 - 1054. [Abstract] [Full Text] [PDF]

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