• Open Access

Temporal requirements of heat shock factor-1 for longevity assurance

Authors

  • Yuli Volovik,

    1. Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel
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    • These authors contributed equally to this work.

  • Moria Maman,

    1. Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel
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    • These authors contributed equally to this work.

  • Tatyana Dubnikov,

    1. Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel
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    • These authors contributed equally to this work.

  • Michal Bejerano-Sagie,

    1. Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel
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  • Derek Joyce,

    1. Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
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  • Erik A Kapernick,

    1. Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
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  • Ehud Cohen,

    1. Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel
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  • Andrew Dillin

    1. Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA
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Ehud Cohen, Biochemistry and Molecular Biology, the Institute for Medical Research Israel – Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel. Tel.: +972-2-6757328; fax: +972-6757326; e-mail: ehudc@ekmd.huji.ac.il
Andrew Dillin, Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. Tel.: +1-858-4534100 ext. 1099; fax: +1-858-5509959; e-mail: dillin@salk.edu

Summary

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.

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