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.AD - Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0554, USA.FAU - Lin, KAU - Lin KFAU - Dorman, J BAU - Dorman JBFAU - Rodan, AAU - Rodan AFAU - Kenyon, CAU - Kenyon CLA - engSI - GENBANK/AF032112ID - AG11816/AG/NIAPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (DAF-16 transcription factor)RN - 0 (DAF-2 protein)RN - 0 (DNA, Complementary)RN - 0 (Nuclear Proteins)RN - 0 (Somatomedins)RN - 0 (Transcription Factors)RN - 0 (forkhead protein)RN - 11061-68-0 (Insulin)RN - EC 2.7.11.- (Receptor, Insulin)SB - IM