Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan in Drosophila

Hina Kosakamoto, Fumiaki Obata (), Junpei Kuraishi, Hide Aikawa, Rina Okada, Joshua N. Johnstone, Taro Onuma, Matthew D. W. Piper and Masayuki Miura ()
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Hina Kosakamoto: The University of Tokyo
Fumiaki Obata: The University of Tokyo
Junpei Kuraishi: The University of Tokyo
Hide Aikawa: The University of Tokyo
Rina Okada: RIKEN Center for Biosystems Dynamics Research
Joshua N. Johnstone: Monash University
Taro Onuma: The University of Tokyo
Matthew D. W. Piper: Monash University
Masayuki Miura: The University of Tokyo

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43550-2

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