Comparative transcriptional profiling identifies takeout as a gene that regulates life span

Abstract

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of humanhealth is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of theproximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changesin gene expression, making it difficult to establish which changes are involved in life span determination as opposed toother unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whosechange in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life spanextending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior andjuvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression andextending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling foridentifying specific downstream elements of the DR life span extending pathway. © Baue et al.