| Project/Area Number |
09835021
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
老化(加齢)
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
HONDA Shuji Tokyo Metropolitan Institute of Gerontology, アイソトープ部門, 研究員 (40100127)
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| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | aging / longevity / life-extension mutant / Mn-SOD / oxidative stress / C. elegans / 線虫 / age-1 / SOD / GFP |
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| Research Abstract |
Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans. Mutations in the daf-2 gene confer the life extension (Age) phenotype and the constitutive dauer formation phenotype. The Age phenotype is mutually potentiated by two life-extension mutations in the daf-2 gene and the clk-1 gene. 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 from daf-2 to the daf-16 gene, a homolog of the HNF-3/ forkhead transcription factor. These findings led us to examine whether the 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 pathway. While 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. These observations suggest that the daf-2 gene network controls longevity by regulating the Mn-SOD-associated antioxidant defense system.
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