• Open Access

Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans

Authors

  • Keunhee Seo,

    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
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  • Eunseok Choi,

    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
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  • Dongyeop Lee,

    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
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  • Dae-Eun Jeong,

    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
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  • Sung Key Jang,

    Corresponding author
    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
    • Correspondence

      Sung Key Jang, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 790-784, South Korea. Tel.:+82-54-279-2258; fax: +82-54-279-8009; e-mail: sungkey@postech.ac.kr and Seung-Jae Lee, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 790-784, South Korea. Tel.: +82-54-279-2351; fax: +82-54-279-2199; e-mail: seungjaelee@postech.ac.kr

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  • Seung-Jae Lee

    Corresponding author
    1. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea
    2. School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea
    • Correspondence

      Sung Key Jang, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 790-784, South Korea. Tel.:+82-54-279-2258; fax: +82-54-279-8009; e-mail: sungkey@postech.ac.kr and Seung-Jae Lee, Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 790-784, South Korea. Tel.: +82-54-279-2351; fax: +82-54-279-2199; e-mail: seungjaelee@postech.ac.kr

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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.

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