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May 15, 2003Science

Regulation of Aging and Age-Related Disease by DAF-16 and Heat-Shock Factor

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Authors

AHAo‐Lin HsuNational Yang Ming Chiao Tung UniversityCMColeen T. MurphyPrinceton UniversityCKCynthia KenyonBuck Institute for Research on Aging

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Implication

Molecular study reveals that HSF-1 and DAF-16 co-regulate lifespan and proteotoxicity in C. elegans, indicating that small heat-shock proteins link normal aging to age-related disease.

Key Points

  • To determine how heat-shock factor HSF-1 interacts with DAF-16 and insulin/IGF-1 signaling to modulate aging and age-dependent proteotoxicity in Caenorhabditis elegans.
  • Measured tissue aging and lifespan in Caenorhabditis elegans models subjected to hsf-1 reduction of function or overexpression.
  • Assessed the epistatic requirement of hsf-1 and daf-16 in long-lived daf-2 insulin/IGF-1 receptor mutant strains.
  • Profiled the expression of downstream target genes, including small heat-shock proteins, and tested their ability to delay polyglutamine-expansion protein aggregation.
  • Reduced hsf-1 activity accelerated tissue decline and shortened lifespan, whereas hsf-1 overexpression extended lifespan.
  • HSF-1, functioning in parallel with DAF-16, was strictly required for daf-2 mutations to confer longevity.
  • HSF-1 and DAF-16 jointly upregulated small heat-shock proteins, which simultaneously promoted longevity and suppressed polyglutamine-expansion aggregation.

Cite This Study

Hsu et al. (2003) studied this question.

synapsesocial.com/papers/6a70a6bfa2d7cf2e39c2b149https://doi.org/10.1126/science.1083701
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Genetic Analysis of Tissue Aging in <i>Caenorhabditis elegans</i>: A Role for Heat-Shock Factor and Bacterial Proliferation2002 · 823 citations
  2. 2Heat Shock Protein Accumulation Is Upregulated in a Long-Lived Mutant of Caenorhabditis elegans2001 · 137 citations
  3. 3The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in <i>Caenorhabditis</i> <i>elegans</i>2002 · 841 citations
  4. 4Changes in Oligomerization Are Essential for the Chaperone Activity of a Small Heat Shock Protein in Vivo and in Vitro2002 · 175 citations
  5. 5Two Pleiotropic Classes of daf-2 Mutation Affect Larval Arrest, Adult Behavior, Reproduction and Longevity in Caenorhabditis elegans1998 · 743 citations