Abstract
Dietary restriction (DR), an intervention commonly used to extend lifespan of both invertebrates and vertebrates, has been shown to reduce insulin/insulin growth factor signaling (IIS) in various organisms. We analyzed the high-throughput gene expression profiling of DR-like Indy mutants and identified Tequila as a candidate gene involved in lifespan regulation. Previous studies have shown that Tequila, a neurotrypsin ortholog, could regulate long-term memory (LTM) formation in Drosophila melanogaster. We found that both hypomorphic mutation of Tequila (Teqf01792), as well as cell-specific down-regulation of Tequila in insulin-producing neurons, significantly induced lifespan extension. Tequila deficiency-induced longevity is likely related to insulin signaling since Teqf01792 mutant flies has displayed several phenotypes of insulin dysfunction, including reduced the level of circulating Drosophila insulin-like peptide 2 (Dilp2), downstream AKT phosphorylation, body weight and altered glucose metabolism. These observations suggest that Tequila may induce lifespan extension through regulation of insulin signaling pathways.