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

作者：Kui Lin, Jennie B. Dorman, Aylin R. Rodan, Cynthia J. Kenyon · 发表于：Science · 年份：1997 · DOI：10.1126/science.278.5341.1319 · 被引用次数：1530 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、FOXO transcription factor regulation、Birth, Development, and Health

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 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.