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

Ao Lin Hsu, Coleen T. Murphy, Cynthia Kenyon

Research output: Contribution to journalArticle

962 Scopus citations

Abstract

The Caenorhabditis elegans transcription factor HSF-1, which regulates the heatshock 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.

Original languageEnglish (US)
Pages (from-to)1142-1145
Number of pages4
JournalScience
Volume300
Issue number5622
DOIs
StatePublished - May 16 2003

All Science Journal Classification (ASJC) codes

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