飲食節制是目前最為人所知延長壽命的方式，在無脊椎動物和脊椎動物都可以觀察到降低飲食攝取量而達到延壽的效果，而且飲食節制在很多的生物體已被證實會降低胰島素的訊號傳遞。我們利用基因表現的方式去分析類似飲食節制表現的Indy突變果蠅，並發現Tequila具有潛力成為新的調控壽命基因。先前研究證實Tequila是一種與哺乳動物同源的神經性胰蛋白脢，調控果蠅長期記憶的形成。我們發現Tequila基因突變和在分泌胰島素的神經細胞中降低Tequila表現量兩者都能誘發延長果蠅壽命的效果。此結果顯示Tequila基因缺失所誘發的長壽現象可能和胰島素訊號傳遞有關，因Teqf01792突變果蠅表現出許多胰島素功能缺失的現象，包括降低循環中第二型類胰島素(Dilp2)的含量、下游AKT分子的磷酸化、體重和改變葡萄醣代謝。這些觀察暗示Tequila誘發壽命延長可能是透由調控胰島素的訊號傳遞。

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.

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