Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.
Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4α-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, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62 mutants. 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 of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span.
Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Bree N
BN
Heestand
Yidong
Y
Shen
Wei
W
Liu
Daniel B
DB
Magner
Nadia
N
Storm
Caroline
C
Meharg
Bianca
B
Habermann
Adam
A
Antebi
D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D031204:Caloric Restriction; D005227:Fatty Acids / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D051557:Hepatocyte Nuclear Factor 4; C585458:NHR-62 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear