Genetic Bases of Oxidative Stress Resistance and Life Span in Drosophila

The fruit fly, Drosophila melanogaster, is an excellent model system for the study of complex biological processes including aging. Through genetic manipulation of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, the roles of these enzymes in oxidative stress resistance and life span determination were established. Transgenic flies overexpressing the enzyme peptide methionine sulfoxide reductase A (MSRA) have been shown to live longer and are more resistant to paraquat-induced oxidative stress. It has been also demonstrated that mutations in genes involved in the insulin/insulin-like growth factor (IGF) pathway (IGF receptor, chico, d FOXO) affected life span and sensitivity to various stresses. We have conducted a conditional gene misexpression screen to identify genes, whose overexpression in adult stages extends life span. Among 13 genes whose functions are known or suggested, six genes were found to be related to stress resistance or redox balance (Dm GST2, hsp26, sra, and Drosophila homologs of mammalian TRX, GILT, and POSH). We recently established a method for the efficient measurement of oxidative stress resistance in Drosophila, using a commercially available activity monitor. The method is suitable for the screening of oxidative stress resistance-related genes using a large number of mutagenized fly lines.