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Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans.

Dietary restriction (DR) has the remarkable ability to extend lifespan and healthspan. A variety of DR regimens have been described in species ranging from yeast to mammals. However, whether different DR regimens extend lifespan via universal, distinct, or overlapping pathways is still an open question. Here we examine the genetic pathways that mediate longevity by different DR regimens in Caenorhabditis elegans. We have previously shown that the low-energy sensing AMP-activated protein kinase AMPK/aak-2 and the Forkhead transcription factor FoxO/daf-16 are necessary for longevity induced by a DR regimen that we developed (sDR). Here we find that AMPK and FoxO are necessary for longevity induced by another DR regimen, but are dispensable for the lifespan extension induced by two different DR methods. Intriguingly, AMPK is also necessary for the lifespan extension elicited by resveratrol, a natural polyphenol that mimics some aspects of DR. Conversely, we test if genes previously reported to mediate longevity by a variety of DR methods are necessary for sDR-induced longevity. Although clk-1, a gene involved in ubiquinone biosynthesis, is also required for sDR-induced lifespan extension, we find that four other genes (sir-2.1, FoxA/pha-4, skn-1, and hsf-1) are all dispensable for longevity induced by sDR. Consistent with the observation that different DR methods extend lifespan by mostly independent genetic mechanisms, we find that the effects on lifespan of two different DR regimens are additive. Understanding the genetic network by which different DR regimens extend lifespan has important implications for harnessing the full benefits of DR on lifespan and healthspan.

Pubmed ID: 19239417

Authors

  • Greer EL
  • Brunet A

Journal

Aging cell

Publication Data

April 2, 2009

Associated Grants

  • Agency: NIA NIH HHS, Id: AG026648-01
  • Agency: NCI NIH HHS, Id: CA09302
  • Agency: NIA NIH HHS, Id: R01 AG026648
  • Agency: NIA NIH HHS, Id: R01 AG026648-01
  • Agency: NIA NIH HHS, Id: R01 AG031198

Mesh Terms

  • Animals
  • Antioxidants
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Caloric Restriction
  • DNA-Binding Proteins
  • Food Deprivation
  • Food, Formulated
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Longevity
  • Protein Kinases
  • Signal Transduction
  • Sirtuins
  • Stilbenes
  • Trans-Activators
  • Transcription Factors