Misexpression screen delineates novel genes controlling Drosophila lifespan

In an initial preliminary screen we identified factors associated with controlling . Drosophila aging by examining longevity in adults where EP elements induced over-expression or antisense-RNA at genes adjacent to each insertion. Here, we study 45 EP lines that initially showed at least 10% longer mean lifespan than controls. These 45 lines and a . daughterless (da)-Gal4 stock were isogenized into a . CS10 wild-type background. Sixteen EP lines corresponding to 15 genes significantly extended lifespan when their target genes were driven by . da-Gal4. In each case, the target genes were seen to be over-expressed. Independently derived UAS-gene transgenic stocks were available or made for two candidates: . ImpL2 which is ecdysone-inducible gene L2, and . CG33138, 1,4-alpha-glucan branching enzyme. With both, adult lifespan was increased upon over-expression via the GeneSwitch inducible Gal4 driver system. Several genes in this set of 15 correspond to previously discovered longevity assurance systems such as insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new potential mechanisms for the control of aging including mRNA synthesis and maturation, intracellular vesicle trafficking, and neuroendocrine regulation.