DAF-16 - AN HNF-3 FORKHEAD FAMILY MEMBER THAT CAN FUNCTION TO DOUBLE THE LIFE-SPAN OF CAENORHABDITIS-ELEGANS/

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 insu lin and insulin-like growth factor receptors, age more slowly than nor mal and live more than twice as long, These mutants are active and ful ly fertile and have normal metabolic rates. The life-span extension ca used 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 expr ession of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been cons erved.