The purpose of the proposal is to find multiple-stress-responsive genes from paraquat, starvation, and heat-treated Drosophila to study their effects on longevity. By using subtractive hybridization and cross hybridization, multiple-stress-responsive cDNA will be identified. Northern blot will be used to confirm the positive cDNA clones. The corresponding gene of each cDNA clone will be searched and cloned. The ability of each multiple- stress-responsive gene to resist stresses and extend longevity in Drosophila will be tested. A genetic screen of mutated flies for stress-resistance will find longevity flies and identify the longevity genes. The discovery of the new genes to increase longevity will help us to better understand the mechanisms of extended life-span.