Publication Date

5-11-2010

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.

Document Type

Article

Keywords

Dietary restriction, Calorie restriction, microarrays, Drosophila melanogaster, Sir2, p53, Rpd3, Indy, methuselah (mth), chico, life span extension, takeout

Disciplines

Biology | Genetics and Genomics

Extent

14 pages

Format

PDF

Rights

© 2010 Bauer et al. Reproduced from AGING, May 2010, Vol. 2, No. 5, pp. 298-310.

Source

AGING

Language

English

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