The insulin-like receptor (DAF-2) mutations in C elegans confer the life extension (Age) phenotype as well as the dauer formation phenotype. We demonstrated that the
daf-2 mutation also confers an oxidative stress resistance (Oxr) phenotype. Similar to the Age phenotype, the Oxr phenotype is regulated by the genetic pathway of insulin-like signaling from DAF-2 to DAF-16. We found that the mRNA level of the
sod-3 , which encodes Mn-superoxide dismutase (SOD), was much higher in
daf-2 mutants than in N2. These observations suggest the possibility that the insulin-like signaling network controls longevity by regulating the Mn-SOD-associated antioxidant defense system. To elucidate the biological roles of two MnSOD isoforms, we isolated deletion mutants of
sod-2 and
sod-3 . We examined the effects of the sod deletion on development, oxidative stress sensitivity, dauer formation and lifespan in N2 and various daf mutants. The growth and fecundity of the
sod-2 mutant were strongly suppressed by hyperoxia compared with the
sod-3 mutant and N2. Hyperoxia was lethal to the double mutant of
sod-2 and
sod-3 . Severity of paraquat toxicity was as follows:
sod-2;
sod-3 >
sod-2 >
sod-3 >N2. The gene expression of
sod-3 was remarkably induced by the
sod-2 deletion. These results suggest that two isoforms of MnSOD mutually function as antioxidant defense. We found that the lifespan of
sod-3 mutant is slightly shorter that that of N2. And the lifespan of
sod-2 mutant is as long as N2. The
sod-2 mutant and
sod-2;
sod-3 double mutant but not
sod-3 mutant show greater sensitivity to hyperoxia than the wild type. The deletion of
sod-2 or
sod-3 gene does not reduce its oxidative stress resistance in
daf-2 mutant. However, triple mutant,
sod-2;
daf-2;
sod-3 shows hyperoxia-sensitivity. The lifespan of
sod-2;
daf-2 double mutant is shorter, while that of
daf-2:
sod-3 double mutant is longer than that of
daf-2 . These results suggest that SOD-3 cooperates with SOD-2 to express Oxr phenotype in
daf-2 mutant but that the Age phenotype of
daf-2 does not link with Oxr phenotype. The effects of the sod deletion on dauer formation in daf mutants were examined. The relationship between reactive oxygen species, development and aging will be discussed.