Application of the gene search system to screen for longevity genes in Drosophila

We have developed a strategy using Drosophila as a model system to identifygenes that are crucial for extension oflongevity. A collection of transgenic lineswith a P -element based gene search (GS)vector containing UAS (Upstream ActivatingSequence) was screened for longevity incombination with an hsp70 promoter-driven GAL4 transgene.Misexpression of the vector-flanking sequencewas induced throughout the adult stage to assessits effects on the aging process rather thandevelopment. We showed that the longevity wasgreatly affected by GS inserts, and it waspositively correlated with paraquatresistance. Of 646 GS inserts, we selected 23inserts with relatively longer longevity forfurther molecular analysis. All of themisexpressed sequences matched either knowngenes or ESTs (Expressed Sequence Tags). Among13 genes whose functions are already known orsuggested, six were related to stressresistance or redox balance ( DmGST2 , hsp26 , nla , and Drosophila homologs of mammalian TRX, GILT and POSH),suggesting the importance of stress resistancefor the extension of longevity. This is thefirst demonstration that a systematicgain-of-function screen could efficientlydetect longevity genes.