Auxin-Inducible Degron System Reveals Temporal-Spatial Roles of HSF-1 and Its Transcriptional Program in Lifespan Assurance.

Autor:	Morphis AC; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States., Edwards SL; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States., Erdenebat P; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States., Kumar L; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States., Li J; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in aging [Front Aging] 2022 Jul 11; Vol. 3, pp. 899744. Date of Electronic Publication: 2022 Jul 11 (Print Publication: 2022).
DOI:	10.3389/fragi.2022.899744
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Morphis, Edwards, Erdenebat, Kumar and Li.)
Databáze:	MEDLINE
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