Research Paper|Volume 2, Issue 5|pp 298—310

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

Johannes Bauer^1,^4,⁵, Michael Antosh^2,^3,⁴, Chengyi Chang¹, Christoph Schorl¹, Santharam Kolli⁵, Nicola Neretti^1,², Stephen L. Helfand¹

¹Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
²Institute for Brain and Neural Systems, Brown University, Providence, RI 02912, USA
³Department of Physics, Brown University, Providence, RI 02912, USA
⁴These authors shared equally in the work
⁵Present address: Department of Biological Sciences, Southern Methodist University, 6501 Airline Drive, 237-DLS, Dallas, TX 75275, USA

Received: May 7, 2010Accepted: May 9, 2010Published: May 11, 2010

https://doi.org/10.18632/aging.100146

Copyright: © 2010 Bauer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change 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 span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile 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 and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway.