Comparative transcriptional profiling identifies takeout as a gene that regulates life span.
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.
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Johannes
J
Bauer
Michael
M
Antosh
Chengyi
C
Chang
Christoph
C
Schorl
Santharam
S
Kolli
Nicola
N
Neretti
Stephen L
SL
Helfand
D000818:Animals; D031204:Caloric Restriction; D002940:Circadian Rhythm / Q000235:genetics; D029382:Dicarboxylic Acid Transporters / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006655:Histone Deacetylases / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics*; D008297:Male; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D037761:Sirtuins / Q000235:genetics; D027981:Symporters / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D029382:Dicarboxylic Acid Transporters; D029721:Drosophila Proteins; C417606:Indy protein, Drosophila; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D027981:Symporters; C411066:TO protein, Drosophila; D016159:Tumor Suppressor Protein p53; C120233:chico protein, Drosophila; C115381:mth protein, Drosophila; C447899:Sirt2 protein, Drosophila; D037761:Sirtuins; D006655:Histone Deacetylases