Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutantsof Caenorhabditis elegans

In the nematode Caenorhabditis elegans, dauer formation, stress resistance, and longevity are determined in part by DAF-2 (insulin receptor-like prote in), AGE-1 (phosphatidylinositol-3-OH kinase catalytic subunit), and DAF-16 (forkhead transcription factor). Mutations in daf-2 and age-1 result in in creased resistance to heat, oxidants, and UV. We have discovered that daf-2 and age-1 mutations result in increased Cd and Cu ion resistance in a 24 h toxicity assay. Lethal concentration (LC50) values for Cd and Cu ions in d af-2 and age-1 mutants were significantly (P<0.001) higher than in wild-typ e nematodes. However, LC50 values in daf-16;age-1 mutants were not signific antly different, implying that metal resistance is influenced by a DAF-16-r elated function. As metallothionein (MT) proteins play a major role in meta l detoxification, we examined the expression of MT genes both under nonindu cing conditions and after exposure to sublethal and acute heavy metal stres s. MT1 mRNA levels were significantly (P<0.05) higher in daf-2 mutants comp ared to age-1 mutants and wild-type C. elegans under basal conditions. Afte r 10 mM Cd treatment, induction of MT1 and MT2 mRNA was three- and twofold higher, respectively, in daf-2 mutant worms than in wild-type. However, a s ublethal concentration of Cd (0.1 mM) resulted in even higher (three- to se venfold) levels of both MT mRNAs in all strains, Cu did not induce MTI or M T2 mRNAs. These results are consistent with a model in which the insulin-si gnaling pathway determines life span through regulation of stress protein g enes.-Barsyte, D., Lovejoy, D. A., Lithgow, G. J. Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans .