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

K Lin, JB Dorman, A Rodan, C Kenyon - Science, 1997 - science.org
K Lin, JB Dorman, A Rodan, C Kenyon
Science, 1997science.org
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
gene daf-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-2 mutations
requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span …
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.
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