Chang Hsin-Yun, McMurry Sarah E, Ma Sicheng, Mansour Christian A, Schwab Sophia Marie T, Danko Charles G, Lee Siu Sylvia
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
Department of Biomedical Science, Cornell University, Ithaca, New York, United States of America.
bioRxiv. 2025 Mar 14:2025.03.11.642714. doi: 10.1101/2025.03.11.642714.
Heat hormesis describes the beneficial adaptations from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. It is thought to be the underlying basis of popular wellness practices like sauna therapy. Despite extensive documentation across species, the molecular basis of the long-term protective effects of heat hormesis remain poorly understood. This study bridges that critical gap through a comprehensive multiomic analysis, providing key insights into the transcriptomic and chromatin accessibility landscapes throughout a heat hormesis regimen adapted in . We uncover highly dynamic dose-dependent molecular responses to heat stress and reveal that while most initial stress-induced changes revert to baseline, key differences in response to subsequent heat shock challenge are directly linked to physiological benefits. We identify new regulators of heat hormesis, including MARS-1/MARS1, SNPC-4/SNAPc, ELT-2/GATA4, FOS-1/c-Fos, and DPY-27/SMC4, which likely orchestrate gene expression programs that enhance stress resilience through distinct biological pathways. This study advances our understanding of stress resilience mechanisms, points to multiple new avenues of future investigations, and suggests potential strategies for promoting healthy aging through mid-life stress management.
热应激预适应描述了短暂暴露于轻度热应激下的有益适应性变化，这种变化可增强应激恢复力并促进健康衰老。它被认为是桑拿疗法等流行健康养生法的潜在基础。尽管在多个物种中都有广泛的文献记载，但热应激预适应长期保护作用的分子基础仍知之甚少。本研究通过全面的多组学分析填补了这一关键空白，为在适应的热应激预适应方案中整个转录组和染色质可及性景观提供了关键见解。我们发现了对热应激高度动态的剂量依赖性分子反应，并揭示虽然大多数初始应激诱导的变化会恢复到基线，但对后续热休克挑战的关键反应差异与生理益处直接相关。我们确定了热应激预适应的新调节因子，包括MARS-1/MARS1、SNPC-4/SNAPc、ELT-2/GATA4、FOS-1/c-Fos和DPY-27/SMC4，它们可能协调基因表达程序，通过不同的生物学途径增强应激恢复力。这项研究推进了我们对应激恢复力机制的理解，指出了未来研究的多个新途径，并提出了通过中年应激管理促进健康衰老的潜在策略。
