The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans.
Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans. Mutations in the daf-2 gene, which encodes a member of the insulin receptor family, confer the life extension (Age) phenotype and the constitutive dauer (a growth-arrested larval form specialized for dispersal) formation phenotype. The Age phenotype is mutually potentiated by two life extension mutations in the daf-2 gene and the clk-1 gene, a homologue of yeast CAT5/COQ7 known to regulate ubiquinone biosynthesis. In this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation. Similar to the Age phenotype, the Oxr phenotype was regulated by the genetic pathway of insulin-like signaling from daf-2 to the daf-16 gene, a homologue of the HNF-3/forkhead transcription factor. These findings led us to examine whether the insulin-like signaling pathway regulates the gene expression of antioxidant defense enzymes. We found that the mRNA level of the sod-3 gene, which encodes Mn-superoxide dismutase (SOD), was much higher in daf-2 mutants than in the wild type. Moreover, the increased sod-3 gene expression phenotype is regulated by the insulin-like signaling pathway. Although the clk-1 mutant itself did not display Oxr and the increased sod-3 expression phenotypes, the clk-1 mutation enhanced them in the daf-2 mutant, suggesting that clk-1 is involved in longevity in two ways: clk-1 composes the original clk-1 longevity program and the daf-2 longevity program. These observations suggest that the daf-2 gene network controls longevity by regulating the Mn-SOD-associated antioxidant defense system. This system appears to play a role in efficient life maintenance at the dauer stage.
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Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan. hondas@center.tmig.or.jp
Honda
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D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D008136:Longevity / Q000235:genetics*; D018384:Oxidative Stress; D011972:Receptor, Insulin / Q000235:genetics*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D013482:Superoxide Dismutase; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin