Morphis Allison C, Edwards Stacey L, Erdenebat Purevsuren, Kumar Lalit, Li Jian
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma, OK, United States.
Front Aging. 2022 Jul 11;3:899744. doi: 10.3389/fragi.2022.899744. eCollection 2022.
HSF-1 is a key regulator of cellular proteotoxic stress response and is required for animal lifespan. In , 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.
热休克因子1（HSF-1）是细胞蛋白质毒性应激反应的关键调节因子，对动物寿命至关重要。在[具体研究中]，HSF-1介导的热休克反应（HSR）在成年期第一天急剧下降，基于RNAi研究提出HSF-1主要在幼虫阶段发挥作用以确保寿命。然而，HSF-1在寿命方面的组织需求尚不清楚。利用生长素诱导降解子（AID）系统，我们成功区分了HSF-1在发育和长寿中的作用。在野生型动物中，我们发现HSF-1在整个自我繁殖期对寿命都是必需的。在生殖系干细胞（GSC）停滞或胰岛素/胰岛素样生长因子-1信号通路（IIS）减弱的长寿动物中，这个时期会延长。虽然在发育过程中从任何主要体细胞组织中去除HSF-1都会导致严重缺陷，但HSF-1主要在成年动物的肠道以及可能的神经系统中发挥作用以维持寿命。最后，通过结合AID和全基因组转录分析，我们发现HSF-1在成年早期直接激活组成型表达的伴侣蛋白和共伴侣蛋白基因等的转录，这是其在寿命保证中发挥作用的基础。
