RRC ID 79015
Author Kosakamoto H, Obata F, Kuraishi J, Aikawa H, Okada R, Johnstone JN, Onuma T, Piper MDW, Miura M.
Title Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan in Drosophila.
Journal Nat Commun
Abstract Methionine 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 known. In Drosophila, 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% extends Drosophila lifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life only robustly extends lifespan. MetR in young flies induces the expression of many longevity-related genes, including Methionine sulfoxide reductase A (MsrA), which reduces oxidatively-damaged Met. MsrA induction is foxo-dependent and persists for two weeks after cessation of the MetR diet. Loss of MsrA attenuates lifespan extension by early-adulthood MetR. Our study highlights the age-dependency of the organismal response to specific nutrients and suggests that nutrient restriction during a particular period of life is sufficient for healthspan extension.
Volume 14(1)
Pages 7832
Published 2023-12-5
DOI 10.1038/s41467-023-43550-2
PII 10.1038/s41467-023-43550-2
PMID 38052797
PMC PMC10698029
MeSH Amino Acids / metabolism Animals Drosophila* / metabolism Longevity* / physiology Methionine / metabolism Methionine Sulfoxide Reductases / genetics Racemethionine
Drosophila DGRC#106500