Regulation of aging and age-related disease by DAF-16 and heat-shock factor.
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.
Pubmed ID: 12750521 RIS Download
Aging | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Forkhead Transcription Factors | Gene Expression Regulation | Heat-Shock Response | Insulin | Longevity | Mutation | Receptor, IGF Type 1 | Receptor, Insulin | Transcription Factors