title: Temporal requirements of heat shock factor-1 for longevity assurance.
abstract: 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.
authors.affiliation: Biochemistry and Molecular Biology, the Institute for Medical Research Israel - Canada (IMRIC), the Hebrew University-Hadassah Faculty of Medicine, Ein-Karem, Jerusalem 91120, Israel.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Volovik
authors.forename: Moria
authors.initials: M
authors.lastname: Maman
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dubnikov
authors.forename: Michal
authors.initials: M
authors.lastname: Bejerano-Sagie
authors.forename: Derek
authors.initials: D
authors.lastname: Joyce
authors.forename: Erik A
authors.initials: EA
authors.lastname: Kapernick
authors.forename: Ehud
authors.initials: E
authors.lastname: Cohen
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D051858:Forkhead Transcription Factors; D055785:Gene Knockdown Techniques; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D012333:RNA, Messenger; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; D007334:Insulin-Like Growth Factor I