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

We have developed a strategy using Drosophilo as a model system to identify genes that are crucial for extension of longevity. A collection of transge nic lines with a P-element based gene search (GS) vector containing UAS (Up stream Activating Sequence) was screened for longevity in combination with an hsp70 promoter-driven GAL4 transgene. Misexpression of the vector-flanki ng sequence was induced throughout the adult stage to assess its effects on the aging process rather than development. We showed that the longevity wa s greatly affected by GS inserts, and it was positively correlated with par aquat resistance. Of 646 GS inserts, we selected 23 inserts with relatively longer longevity for further molecular analysis. All of the misexpressed s equences matched either known genes or ESTs (Expressed Sequence Tags). Amon g 13 genes whose functions are already known or suggested, six were related to stress resistance or redox balance (DmGST2, hsp26, nla, and Drosophila homologs of mammalian TR GILT and POSH), suggesting the importance of stres s resistance for the extension of longevity. This is the first demonstratio n that a systematic gain-of-function screen could efficiently detect longev ity genes.