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. © 2013 heestand et al.