Histone acetylation promotes long-lasting defense responses and longevity following early life heat stress
Histone acetylation promotes long-lasting defense responses and longevity following early life heat stress
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组蛋白乙酰化可促进生命早期热应激后的持久防御反应和寿命
DOI：
10.1371/journal.pgen.1008122
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发表时间：
2019-04
期刊：
影响因子：
4.5
通讯作者：
Tang Haiqing
中科院分区：
文献类型：
--
作者：
Zhou Lei;He Bin;Deng Jianhui;Pang Shanshan;Tang Haiqing
早期接触一些轻微的压力可以减缓衰老过程并延长寿命，这就提出了早期生活压力如何影响老年动物的身体健康的问题。在这里，我们揭示了生命早期的高温经历触发了体细胞表观遗传记忆的建立，这促进了秀丽隐杆线虫持久的应激反应和长寿。与致死性热休克不同，温和的高温激活了一个独特的转录程序，模仿病原体的防御反应，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持续很长时间，即使在年老的动物中也能增强抗逆性。进一步的研究发现组蛋白乙酰转移酶CBP-1和染色质重塑SWI/SNF复合物是持久防御反应的表观遗传调节剂。组蛋白乙酰化在热应激下升高，并维持到老年。因此，防御基因启动子上的组蛋白乙酰化水平升高。此外，表观遗传记忆的破坏破坏了对早期热应激的长寿反应，表明持久的防御反应对老年动物的生存至关重要。总之，我们的发现提供了关于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的机制见解。
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.
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作者：
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