Developmental ROS individualizes organismal stress resistance and lifespan

被引：178

作者：

Bazopoulou, Daphne ^{[1
]}

Knoefler, Daniela ^{[1
]}

Zheng, Yongxin ^{[2
,3
]}

Ulrich, Kathrin ^{[1
]}

Oleson, Bryndon J. ^{[1
]}

Xie, Lihan ^{[1
]}

Kim, Minwook ^{[1
]}

Kaufmann, Anke ^{[1
]}

Lee, Young-Tae ^{[4
]}

Dou, Yali ^{[4
]}

Chen, Yong ^{[5
]}

Quan, Shu ^{[2
,3
]}

Jakob, Ursula ^{[1
]}

机构：

[1] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA

[2] East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China

[3] SCICB, Shanghai, Peoples R China

[4] Michigan Med, Dept Pathol, Ann Arbor, MI USA

[5] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Natl Ctr Prot Sci Shanghai, Shanghai, Peoples R China

来源：

NATURE | 2019年 / 576卷 / 7786期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

OXIDATIVE STRESS; GENETICS; RESTRICTION; RESPIRATION; MECHANISMS; FAMILY; EVENT;

D O I：

10.1038/s41586-019-1814-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A central aspect of aging research concerns the question of when individuality in lifespan arises(1). 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.

引用

页码：301 / +

页数：20

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