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daf-16: An HNF-3/forkhead Family Member That Can Function to Double the Life-Span of Caenorhabditis elegans

Science  14 Nov 1997:
Vol. 278, Issue 5341, pp. 1319-1322
DOI: 10.1126/science.278.5341.1319

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Abstract

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the genedaf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2mutations requires the activity of the gene daf-16. daf-16appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

  • * Present address: Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195– 7275, USA.

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