School of Life Sciences, Chongqing University, Chongqing, China.
PLoS Genet. 2019 Apr 29;15(4):e1008122. doi: 10.1371/journal.pgen.1008122. eCollection 2019 Apr.
Early exposure to some mild stresses can slow down the aging process and extend lifespan, raising the question of how early life stress might impact the somatic health of aged animals. Here, we reveal that early life heat experience triggers the establishment of epigenetic memory in soma, which promotes long-lasting stress responses and longevity in C. elegans. Unlike lethal heat shock, mild heat activates a unique transcriptional program mimicking pathogen defense responses, characterized by the enhanced expression of innate immune and detoxification genes. Surprisingly, the expression of defense response genes persists long after heat exposure, conferring enhanced stress resistance even in aged animals. Further studies identify the histone acetyltransferase CBP-1 and the chromatin remodeling SWI/SNF complex as epigenetic modulators of the long-lasting defense responses. Histone acetylation is elevated by heat stress and maintained into agedness thereafter. Accordingly, histone acetylation levels were increased on the promoters of defense genes. Moreover, disruption of epigenetic memory abrogates the longevity response to early hormetic heat stress, indicating that long-lasting defense responses are crucial for the survival of aged animals. Together, our findings provide mechanistic insights into how temperature stress experienced in early life provides animals with lifetime health benefits.
早期接触一些轻度压力可以减缓衰老过程并延长寿命，这就提出了一个问题，即早期生活压力如何影响老年动物的身体健康。在这里，我们揭示了早期的热体验会在体细胞中引发表观遗传记忆的建立，从而促进秀丽隐杆线虫的持久应激反应和长寿。与致命的热休克不同，轻度热激活了一个独特的转录程序，模拟病原体防御反应，其特征是先天免疫和解毒基因的表达增强。令人惊讶的是，防御反应基因的表达在热暴露后很长一段时间内持续存在，即使在老年动物中也赋予了增强的应激抗性。进一步的研究确定了组蛋白乙酰转移酶 CBP-1 和染色质重塑 SWI/SNF 复合物作为持久防御反应的表观遗传调节剂。热应激会导致组蛋白乙酰化水平升高，并在此后维持到老年。因此，防御基因的启动子上的组蛋白乙酰化水平增加。此外，破坏表观遗传记忆会消除早期有益热应激对长寿的反应，表明持久的防御反应对老年动物的生存至关重要。总之，我们的研究结果为早期生活中经历的温度应激如何为动物提供终身健康益处提供了机制上的见解。
