Regulation of aging and age-related disease by DAF-16 and heat-shock factor

Science. 2003 May 16;300(5622):1142-5. doi: 10.1126/science.1083701.

Abstract

The Caenorhabditis elegans transcription factor HSF-1, which regulates the heat-shock response, also influences aging. Reducing hsf-1 activity accelerates tissue aging and shortens life-span, and we show that hsf-1 overexpression extends lifespan. We find that HSF-1, like the transcription factor DAF-16, is required for daf-2-insulin/IGF-1 receptor mutations to extend life-span. Our findings suggest this is because HSF-1 and DAF-16 together activate expression of specific genes, including genes encoding small heat-shock proteins, which in turn promote longevity. The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease.

Publication types

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

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Heat-Shock Response / genetics
  • Heat-Shock Response / physiology
  • Insulin / genetics
  • Insulin / physiology
  • Longevity / genetics
  • Longevity / physiology
  • Mutation
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology
  • Transcription Factors / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • daf-16 protein, C elegans
  • heat shock factor-1, C elegans
  • DAF-2 protein, C elegans
  • Receptor, IGF Type 1
  • Receptor, Insulin