Affiliation:
1. Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143–0554, USA.
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 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.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
1352 articles.
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