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

Authors: Lapierre LR; Gelino S; Meléndez A; Hansen M

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.

Keywords: Aging/genetics/*physiology; Animals; Autophagy/*physiology; Caenorhabditis elegans/*cytology/metabolism/physiology; Caenorhabditis elegans Proteins/genetics/metabolism/*physiology; Gene Expression Regulation, Developmental; Germ Cells/physiology; Lipase/genetics/metabolism/*physiology; Lipid Metabolism; Longevity; Phosphotransferases (Alcohol Group Acceptor)/genetics/metabolism/physiology; Trans-Activators/metabolism/physiology
Journal: Current biology : CB
Volume: 21
Issue: 18
Pages: 1507-14
Date: Sept. 13, 2011
PMID: 21906946
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Citation:

Lapierre LR, Gelino S, Meléndez A, Hansen M (2011) Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Current biology : CB 21: 1507-14.


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