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Journal Article

Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans


Heestand,  B. N.
Max Planck Society;

Shen,  Y.
Max Planck Society;

Liu,  W.
Max Planck Society;

Magner,  D. B.
Max Planck Society;

Storm,  N.
Max Planck Society;

Meharg,  C.
Max Planck Society;

Habermann,  B.
Max Planck Society;

Antebi,  A.
Max Planck Society;

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Heestand, B. N., Shen, Y., Liu, W., Magner, D. B., Storm, N., Meharg, C., et al. (2013). Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans. PLoS Genet, 9(7), e1003651. doi:10.1371/journal.pgen.1003651.

Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-5904-A
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 HNF4alpha-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.