Caenorhabditis elegans

Epigenetics

Reactive oxygen species

Biology

Promoter

Gene

Cell biology

Gene expression

H3K4me3

Histone

Histone methyltransferase

Genetics

Nature

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.

Developmental ROS individualizes organismal stress resistance and lifespan