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

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.

Pubmed ID: 21906946


  • Lapierre LR
  • Gelino S
  • Meléndez A
  • Hansen M


Current biology : CB

Publication Data

September 27, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: P30 CA030199
  • Agency: NIA NIH HHS, Id: R01 AG039756

Mesh Terms

  • Aging
  • Animals
  • Autophagy
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Gene Expression Regulation, Developmental
  • Germ Cells
  • Lipase
  • Lipid Metabolism
  • Longevity
  • Phosphotransferases (Alcohol Group Acceptor)
  • Trans-Activators