Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster

Abstract

The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling.

Keywords: Aging; Glucose homeostasis; Longevity; Neurotrypsin.