title: Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans.
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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Seo
authors.forename: Eunseok
authors.initials: E
authors.lastname: Choi
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.forename: Dae-Eun
authors.initials: DE
authors.lastname: Jeong
authors.forename: Sung Key
authors.initials: SK
authors.lastname: Jang
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015536:Down-Regulation; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D051379:Mice; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D010455:Peptides / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D010455:Peptides; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; C097188:polyglutamine; D007334:Insulin-Like Growth Factor I; D017853:Phosphotransferases (Alcohol Group Acceptor); C472494:let-363 protein, C elegans; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C571892:Rsks-1 protein, C elegans
keywords: Caenorhabditis elegans; HSF-1; S6 kinase; aging; insulin/IGF-1 signaling; longevity; mRNA translation; target of rapamycin