Aging and resistance to oxidative damage in Caenorhabditis elegans.
The dauer larva state and the age-1 mutation, both of which extend life-span in Caenorhabditis elegans, were tested for hyperresistance to cellular damage that may be relevant to aging. The age-1 strain TJ401 displayed hyperresistance to oxidative stress relative to its parental strain. The activities of two enzymes that protect cells from oxidative damage, superoxide dismutase (SOD) and catalase, showed an age-dependent increase in mutant animals, which was not seen in the parental strain. These increases in activities paralleled the time course of the hyperresistance. The results are consistent with the age-1 gene product functioning as a negative regulator of SOD and catalase activities. In wild-type and age-1 dauer larvae, elevated levels of SOD activity, but not of catalase activity, were present when compared with young adults. The common increase in SOD activity prompted cloning the C. elegans Cu/Zn SOD gene. Its position on the physical map of the genome was in the region to which the age-1 gene has been genetically mapped, but it is unlikely that a mutation at the SOD locus confers the Age phenotype. Results support the free radical theory of aging by suggesting that the increased resistance to oxidative stress may be among the causes of increased longevity in both strain TJ401 and in the dauer larva.
Larsen
P L
PL
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
D000375:Aging / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D002374:Catalase / Q000378:metabolism; D002874:Chromosome Mapping; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007814:Larva; D008969:Molecular Sequence Data; D016877:Oxidants / Q000633:toxicity*; D017386:Sequence Homology, Amino Acid; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
D016877:Oxidants; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase