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Curr Biol. 2011 Sep 27;21(18):1507-14. doi: 10.1016/j.cub.2011.07.042. Epub 2011 Sep 8.

Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans.

Author information

1
Program of Development and Aging, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, USA.

Abstract

BACKGROUND:

The cellular recycling process of autophagy is emerging as a key player in several longevity pathways in Caenorhabditis elegans. Here, we identify a role for autophagy in long-lived animals lacking a germline and show that autophagy and lipid metabolism work interdependently to modulate aging in this longevity model.

RESULTS:

Germline removal extends life span in C. elegans via genes such as the lipase LIPL-4; however, less is known of the cellular basis for this life-span extension. Here, we show that germline loss induces autophagy gene expression via the forkhead box A (FOXA) transcription factor PHA-4 and that autophagy is required to extend longevity. We identify a novel link between autophagy and LIPL-4, because autophagy is required to maintain high lipase activity in germline-deficient animals. Reciprocally, lipl-4 is required for autophagy induction. Coordination between autophagy and lipolysis is further supported by the finding that inhibition of TOR (target of rapamycin), a major negative regulator of autophagy, induces lipl-4 expression, and TOR levels are reduced in germline-less animals. TOR may therefore function as a common upstream regulator of both autophagy and lipl-4 expression in germline-less animals. Importantly, we find that the link between autophagy and LIPL-4 is relevant to longevity, because autophagy is induced in animals overexpressing LIPL-4 and autophagy is required for their long life span, recapitulating observations in germline-less animals.

CONCLUSIONS:

Collectively, our data offer a novel mechanism by which autophagy and the lipase LIPL-4 interdependently modulate aging in germline-deficient C. elegans by maintaining lipid homeostasis to prolong life span.

PMID:
21906946
PMCID:
PMC3191188
DOI:
10.1016/j.cub.2011.07.042
[Indexed for MEDLINE]
Free PMC Article

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