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发育活性氧个体化机体抗应激与寿命
2019-12-06 11:13

近日,美国密歇根大学Ursula Jakob及其研究组发现,发育过程中产生的活性氧使机体的抗应激能力和寿命发生个体化。2019年12月4日,《自然》在线发表了这一成果。

衰老研究的一个主要方面是寿命中何时出现个体性。研究人员表明,在早期发育中的线虫秀丽隐杆线虫亚群中自然发生的活性氧(ROS)的瞬时增加,使应激抗逆性增加,改善了氧化还原稳态并最终延长了这些动物的寿命。

研究人员发现这些影响与全局性ROS介导的发育组蛋白H3K4me3水平下降有关。对HeLa细胞的研究证实,总体H3K4me3水平对ROS敏感,并且H3K4me3水平的耗竭会增加哺乳动物细胞的抗逆性。体外研究确定SET1/MLL组蛋白甲基转移酶是H3K4三甲基化蛋白复合物(COMPASS)的氧化还原敏感单位。这些发现暗示了生命早期事件的联系,即在ROS敏感性表观遗传标记、抗逆性与寿命之间。

附:英文原文

Title: Developmental ROS individualizes organismal stress resistance and lifespan

Author: Daphne Bazopoulou, Daniela Knoefler, Yongxin Zheng, Kathrin Ulrich, Bryndon J. Oleson, Lihan Xie, Minwook Kim, Anke Kaufmann, Young-Tae Lee, Yali Dou, Yong Chen, Shu Quan, Ursula Jakob

Issue&Volume: 2019-12-04

Abstract: A central aspect of aging research concerns the question of when individuality in lifespan arises1. Here we show that a transient increase in reactive oxygen species (ROS), which occurs naturally during early development in a subpopulation of synchronized Caenorhabditis elegans, sets processes in motion that increase stress resistance, improve redox homeostasis and ultimately prolong lifespan in those animals. We find that these effects are linked to the global ROS-mediated decrease in developmental histone H3K4me3 levels. Studies in HeLa cells confirmed that global H3K4me3 levels are ROS-sensitive and that depletion of H3K4me3 levels increases stress resistance in mammalian cell cultures. In vitro studies identified SET1/MLL histone methyltransferases as redox sensitive units of the H3K4-trimethylating complex of proteins (COMPASS). Our findings implicate a link between early-life events, ROS-sensitive epigenetic marks, stress resistance and lifespan. A subpopulation of Caenorhabditis elegans, in which there is a naturally occurring transient increase in reactive oxygen species during early development, exhibits increased stress resistance, improved redox homeostasis and prolonged lifespan, which are linked to a global decrease in level of the histone mark H3K4me3.

DOI: 10.1038/s41586-019-1814-y

Source:https://www.nature.com/articles/s41586-019-1814-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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