Temporal requirements of heat shock factor-1 for longevity assurance

Yuli Volovik, Moria Maman, Tatyana Dubnikov, Michal Bejerano-Sagie, Derek Joyce, Erik A. Kapernick, Ehud Cohen*, Andrew Dillin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Reducing the activity of the insulin/IGF-1 signaling pathway (IIS) modifies development, elevates stress resistance, protects from toxic protein aggregation (proteotoxicity), and extends lifespan (LS) of worms, flies, and mice. In the nematode Caenorhabditis elegans, LS extension by IIS reduction is entirely dependent upon the activity of the transcription factors DAF-16 and the heat shock factor-1 (HSF-1). While DAF-16 determines LS exclusively during early adulthood, it is required for proteotoxicity protection also during late adulthood. In contrast, HSF-1 protects from proteotoxicity during larval development. Despite the critical requirement for HSF-1 for LS extension, the temporal requirements for this transcription factor as a LS determinant are unknown. To establish the temporal requirements of HSF-1 for longevity assurance, we conditionally knocked down hsf-1 during larval development and adulthood of C. elegans and found that unlike daf-16, hsf-1 is foremost required for LS determination during early larval development, required for a lesser extent during early adulthood and has small effect on longevity also during late adulthood. Our findings indicate that early developmental events affect LS and suggest that HSF-1 sets during development of the conditions that enable DAF-16 to promote longevity during reproductive adulthood. This study proposes a novel link between HSF-1 and the longevity functions of the IIS.

Original languageAmerican English
Pages (from-to)491-499
Number of pages9
JournalAging Cell
Volume11
Issue number3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Aging
  • DAF-16
  • Development
  • Heat shock factor 1
  • Insulin/IGF-1 signaling

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