Developmental ROS individualizes organismal stress resistance and lifespan.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Longevity* ; Oxidative Stress*; Reactive Oxygen Species/*metabolism; Animals ; Caenorhabditis elegans ; Down-Regulation ; Histones/metabolism ; Larva

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.

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R01 AG027349 United States AG NIA NIH HHS; AG046799 United States NH NIH HHS; R35 GM122506 United States GM NIGMS NIH HHS; R21 AG046799 United States AG NIA NIH HHS; GM122506 United States NH NIH HHS; P40 OD010440 United States OD NIH HHS

0 (Histones)
0 (Reactive Oxygen Species)
0 (histone H3 trimethyl Lys4)

Date Created: 20191206 Date Completed: 20200402 Latest Revision: 20220417

20240513

PMC7039399

10.1038/s41586-019-1814-y

31801997