Genetic screen to identify genes that regulate life span in drosophila melanogaster

Abstract

Abstract

Ageing is usually defined as the progressive loss of function accompanied by decreasing fertility and increasing mortality with advancing age. At present the precise mechanisms that determine how organisms senesce and die are unknown. However, the fact that individual species have characteristic life spans ranging from 70 to 80 days in the fruit fly, Drosophila melanogaster, to 80 years for humans, yet share similar features during ageing, suggests the existence of common mechanisms which determine both the rate of ageing and the life span of an organism. Studies in model organisms such as Caenorhabditis elegans, Drosophila melanogaster and mice have proven particularly useful in identifying some of the mechanisms that affect life span. These studies have the great advantage that one can use genetic approaches to search directly for such mutations that change life span. This makes it possible to identify mechanisms in a way that is independent of any preconceived model of ageing. Recently, the analysis of such mutations that affect life span has revealed several different pathways that influence the ageing process. In this study, to elucidate the genetic pathways and molecular mechanisms underlying ageing, a large-scale genetic screen has been performed using D. melanogaster and the GAL4/UAS system. We screened 17,475 EPs and selected 388 lines. Among them, 209 lines were retested and 20 lines that show increased mean life span were identified. Analysis of genomic regions adjacent to these EPs defined 18 genes that exhibit increased mean life span. Seven of these (known genes) have published mutant alleles; the other 12 (new genes) have not been characterized genetically. The proteins encoded by the 18 identified genes include proteins involved in glucose metabolism or in chromosome remodeling, a kinase, and structural proteins.