It has been previously demonstrated that activities of the anti-oxidant enzymes catalase and superoxide dismutase are increased in some long-lived daf-c mutant animals. We have discovered that catalase activity is increased in starving animals as compared to well fed controls and that this increase in activity is
daf-16 dependent. This finding prompts the speculation that similar mechanisms underlie life-span extension both, during caloric restriction and in daf-c mutant animals. We have found that C. elegans, contains two genes coding for distinct isoforms of catalase. The
ctl-2 gene encodes an isoform of catalase, which like catalases studied thus far in mammalian cell types, is localized to peroxisomes. However, the
ctl-1 gene encodes a cytosolic catalase. This is the first molecular genetic evidence for the presence of genes coding for cytosolic and peroxisomal catalases in animal cells, analogous to that seen in fungal and plant cells. Northern analysis has shown that
ctl-2 mRNA abundance decreases as wild type and
age-1 animals age. In contrast, the abundance of
ctl-1 mRNA is strongly up-regulated in long-lived
age-1 animals and in
daf-2 dauer larvae, suggesting a role for the
ctl-1 catalase in
age-1/daf-2 dependent life-span extension. We obtained a
ctl-1 mutation serendipitously that contained a single basepair deletion that introduces an early stop codon. This mutation is likely null. Using a subtractive cDNA screen, an animal carrying a mutation in the
ctl-1 gene was identified. The mutation was determined to be a single basepair deletion that introduces a stop codon and a truncation of the
ctl-1 protein consistent with a
ctl-1 null mutation. Total catalase activity in the
ctl-1 mutant is reduced by ~50% as compared with wild type. The
ctl-1 mutation reduces the mean life-span of wild type animals by approximately 30%. Double and triple mutants containing life-span extending daf-c mutations and
ctl-1 mutations live no longer than those carrying the
ctl-1 mutation alone. This result indicates that
ctl-1 is necessary for the life-span extension seen in long-lived daf-c animals. We hypothesize that the
ctl-1 catalase has evolved to cope with oxidative stress during the extended period of pre-reproductive dormancy in dauer larvae. Moreover, misexpression of
ctl-1 and possibly other anti-oxidant enzymes in the long-lived daf-c mutants is necessary for the life-span extension seen in these mutants.