FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgeneexpression can extend the life span of adult Drosophila melanogaster flies

Yeast FLP recombinase was used in a binary transgenic system ("FLP-OUT") to allow induced overexpression of catalase and/or Cu/Zn-superoxide dismutase (Cu/ZnSOD) in adult Drosophila melanogaster. Expression of FLP recombinase was driven by the heat-inducible hsp70 promoter. Once expressed, FLP catal yzed the rearrangement and activation of a target construct in which expres sion of catalase or Cu/ZnSOD cDNAs was driven by the constitutive actin5C p romoter. In this way a brief heat pulse (120 or 180 min, total) of young ad ult flies activated transgene expression for the rest of the life span. FLP -OUT allows the effects of induced transgene expression to be analyzed in c ontrol (no heat pulse) and experimental (heat pulse) populations with ident ical genetic backgrounds. Under the conditions used, the heat pulse itself always had neutral or slightly negative effects on the life span. Catalase overexpression significantly increased resistance to hydrogen peroxide but had neutral or slightly negative effects on the mean life span. Cu/ZnSOD ov erexpression extended the mean life span up to 48%. Simultaneous overexpres sion of catalase with Cu/ZnSOD had no added benefit, presumably due to a pr eexisting excess of catalase. The data suggest that oxidative damage is one rate-limiting factor for the life span of adult Drosophila. Finally, exper imental manipulation of the genetic background demonstrated that the life s pan is affected by epistatic interactions between the transgene and allele( s) at other loci.