Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan inDrosophila

Abstract

AbstractMethionine restriction (MetR) extends lifespan in various organisms, but its mechanistic understanding remains incomplete. Whether MetR during a specific period of adulthood increases lifespan is not shown. InDrosophila, MetR is reported to extend lifespan only when amino acid levels are low. Here, by using an exome-matched holidic medium, we show that decreasing Met levels to 10% extendsDrosophilalifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life robustly extends lifespan. MetR induces the expression ofMethionine sulfoxide reductase A(MsrA) in young flies, which reduces the oxidatively-damaged Met.MsrAinduction isfoxo-dependent and persists for two weeks after cessation of the MetR diet. Loss ofMsrAattenuates lifespan extension by early-adult MetR. Our study highlights the age-dependency of the organismal response to specific nutrient and suggests that nutrient restriction at a particular period of life is sufficient for healthspan extension.