RRC ID 46188
Author Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ.
Title Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans.
Journal Aging Cell
Abstract Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.
Volume 12(6)
Pages 1073-81
Published 2013-12-1
DOI 10.1111/acel.12140
PMID 23879233
MeSH Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / antagonists & inhibitors* Caenorhabditis elegans Proteins / metabolism* Down-Regulation Insulin / metabolism* Insulin-Like Growth Factor I / metabolism* Longevity* Mice Mutation / genetics Oxidative Stress Peptides / metabolism Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors* Phosphotransferases (Alcohol Group Acceptor) / metabolism Protein Structure, Quaternary Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors Ribosomal Protein S6 Kinases, 70-kDa / metabolism Signal Transduction* Transcription Factors / metabolism*
IF 7.238
Times Cited 59
C.elegans tm1714