AUTHOR=Morphis Allison C. , Edwards Stacey L. , Erdenebat Purevsuren , Kumar Lalit , Li Jian TITLE=Auxin-Inducible Degron System Reveals Temporal-Spatial Roles of HSF-1 and Its Transcriptional Program in Lifespan Assurance JOURNAL=Frontiers in Aging VOLUME=3 YEAR=2022 URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.899744 DOI=10.3389/fragi.2022.899744 ISSN=2673-6217 ABSTRACT=

HSF-1 is a key regulator of cellular proteotoxic stress response and is required for animal lifespan. In C. elegans, HSF-1 mediated heat shock response (HSR) declines sharply on the first day of adulthood, and HSF-1 was proposed to function primarily during larval stages for lifespan assurance based on studies using RNAi. The tissue requirement for HSF-1 in lifespan, however, is not well understood. Using the auxin-inducible degron (AID) system, we manage to uncouple the roles of HSF-1 in development and longevity. In wild-type animals, we find HSF-1 is required during the whole self-reproductive period for lifespan. This period is extended in long-lived animals that have arrested germline stem cells (GSC) or reduced insulin/IGF-1 signaling (IIS). While depletion of HSF-1 from any major somatic tissues during development results in severe defects, HSF-1 primarily functions in the intestine and likely neural system of adults to support lifespan. Finally, by combining AID and genome-wide transcriptional analyses, we find HSF-1 directly activates the transcription of constitutively-expressed chaperone and co-chaperone genes among others in early adulthood, which underlies its roles in longevity assurance.