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Nature. 2019 Dec;576(7786):301-305. doi: 10.1038/s41586-019-1814-y. Epub 2019 Dec 4.

Developmental ROS individualizes organismal stress resistance and lifespan.

Author information

1
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
2
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
3
Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), Shanghai, China.
4
Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.
5
State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
6
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. ujakob@umich.edu.

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.

PMID:
31801997
DOI:
10.1038/s41586-019-1814-y

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