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

TitleRegulation of aging and age-related disease by DAF-16 and heat-shock factor.
Publication TypeJournal Article
Year of Publication2003
AuthorsHsu A-L, Murphy CT, Kenyon C
JournalScience
Volume300
Issue5622
Pagination1142-5
Date Published2003 May 16
ISSN1095-9203
KeywordsAging, 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
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.

DOI10.1126/science.1083701
Alternate JournalScience
Full Text
PubMed ID12750521