Dietary Restriction Induced Longevity is Mediated by Nuclear Receptor NHR-62 in Caenorhabditis elegans

Bree Heestand, Yidong Shen, Wei Liu, Daniel Magner, Nadia Storm, Caroline Meharg (nee Reiff), Bianca Habermann, Adam Antebi

Research output: Contribution to journalArticle

45 Citations (Scopus)
460 Downloads (Pure)

Abstract

Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the C. elegans HNF4a- related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat- 2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, increased autophagy, and changes in fatty acid composition are partly reversed by mutation of nhr-62. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence that nuclear hormone receptors regulate the DR response, suggesting hormonal and metabolic control of life span.
Original languageEnglish
Article numbere1003651
Pages (from-to)e1003651
JournalPLoS Genetics
Volume9
Issue number7
Early online date25 Jul 2013
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

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