daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans

Science. 1997 Nov 14;278(5341):1319-22. doi: 10.1126/science.278.5341.1319.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins*
  • Cloning, Molecular
  • DNA, Complementary
  • Forkhead Transcription Factors
  • Genes, Helminth
  • Humans
  • Insulin / physiology
  • Longevity / genetics
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Phenotype
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology
  • Sequence Alignment
  • Somatomedins / physiology
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Complementary
  • Forkhead Transcription Factors
  • Insulin
  • Nuclear Proteins
  • Somatomedins
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin

Associated data

  • GENBANK/AF032112