Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways inC. elegans
| Autor: | Dae-Eun Jeong, Keunhee Seo, Sung Key Jang, Seung-Jae Lee, Eunseok Choi, Dongyeop Lee |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Aging
media_common.quotation_subject Longevity Down-Regulation P70-S6 Kinase 1 Biology Mice Animals Insulin Insulin-Like Growth Factor I Caenorhabditis elegans Caenorhabditis elegans Proteins Protein Structure Quaternary HSF1 Transcription factor media_common Genetics Ribosomal Protein S6 Kinases 70-kDa Cell Biology biology.organism_classification Cell biology TOR signaling Oxidative Stress Phosphotransferases (Alcohol Group Acceptor) Ribosomal protein s6 Mutation Signal transduction Peptides Signal Transduction Transcription Factors |
| Zdroj: | Aging Cell. 12:1073-1081 |
| ISSN: | 1474-9718 |
| DOI: | 10.1111/acel.12140 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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