An AMPK-FOXO Pathway Mediates Longevity Induced by a Novel Method of Dietary Restriction in C. Elegans

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2007 Sep 29

PMID 17900900

Citations 425

Authors

Eric L Greer

Dara Dowlatshahi

Max R Banko

Judit Villen

Kimmi Hoang

Daniel Blanchard

Steven P Gygi

Anne Brunet

Affiliations

Soon will be listed here.

Abstract

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.

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