Your browser version may not work well with NCBI's Web applications. More information here...
1: Curr Biol. 2007 Oct 9;17(19):1646-56. Epub 2007 Sep 27.
Related Articles, Links
Click here to read Click here to read Click here to read
An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans.

Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A.

Department of Genetics, Cancer Biology Program, Stanford University, Stanford, California 94305, USA.

BACKGROUND: Dietary restriction (DR) is the most effective environmental intervention to extend lifespan in a wide range of species. However, the molecular mechanisms underlying the benefits of DR on longevity are still poorly characterized. AMP-activated protein kinase (AMPK) is activated by a decrease in energy levels, raising the possibility that AMPK might mediate lifespan extension by DR. RESULTS: By using a novel DR assay that we developed and validated in C. elegans, we find that AMPK is required for this DR method to extend lifespan and delay age-dependent decline. We find that AMPK exerts its effects in part via the FOXO transcription factor DAF-16. FOXO/DAF-16 is necessary for the beneficial effects of this DR method on lifespan. Expression of an active version of AMPK in worms increases stress resistance and extends longevity in a FOXO/DAF-16-dependent manner. Lastly, we find that AMPK activates FOXO/DAF-16-dependent transcription and phosphorylates FOXO/DAF-16 at previously unidentified sites, suggesting a possible direct mechanism of regulation of FOXO/DAF-16 by AMPK. CONCLUSIONS: Our study shows that an energy-sensing AMPK-FOXO pathway mediates the lifespan extension induced by a novel method of dietary restriction in C. elegans.

Publication Types:
PMID: 17900900 [PubMed - indexed for MEDLINE]

PMCID: PMC2185793