High-throughput screening of genes regulating drosopila life span

Abstract

Ageing is defined as the process of maturing or growing old. It is usually accompanied with decreasing physiological vigor and increasing mortality with age. Ageing is considered to be determined by environmental factors or genetic factors under complicated regulations. However, recently it has been reported that single gene mutations extended life span dramatically in many organisms, suggesting that the ageing process is subject to regulation. In the present study, in order to find the genetic pathways and molecular mechanisms of ageing, high-throughput genetic screen was carried out in the fruit fly, Drosophila melanogaster using hs-GAL4 or tet-on-GAL4/UAS system. By hs-GAL4 driver 29,790 EP lines were screened, and 344 lines were seleted. The selected lines were retested by tet-on-gal4 driver and finally 41 EP insertion lines that showed increased mean life span were confirmed. We examined the genome sequences flanking each EP insertion and identified 32 genes affected by these EPs. Functions of 23 genes were known; 9 genes have not been characterized genetically. The proteins encoding the 18 identified genes are involved in signal pathway, metabolism, transcription and translation machineries, ion transporting, cytoskeleton, and cell cycle regulation. Still have we a long way to set a central hypothesis, and to understand the key mechanism of ageing. But life span extension phenotypes of mutant EP lines shoul be a useful tool in order to understand ageing processes.