TY - JOUR
T1 - Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan in Drosophila
AU - Kosakamoto, Hina
AU - Obata, Fumiaki
AU - Kuraishi, Junpei
AU - Aikawa, Hide
AU - Okada, Rina
AU - Johnstone, Joshua N.
AU - Onuma, Taro
AU - Piper, Matthew D.W.
AU - Miura, Masayuki
N1 - Funding Information:
The authors would like to acknowledge Kyoto Stock Center, National Institute of Genetics, Vienna Drosophila Resource Center, and Bloomington Drosophila Stock Center for reagents. We thank Takao Fujisawa, Yoriko Akuzawa, and all the members of Miura’s laboratory and Obata’s laboratory for technical assistance and critical advice. We thank Sa Kan Yoo and Scott Pletcher for the critical reading of the manuscript. This work was supported by AMED-PRIME to F.O. under Grant Number JP20gm6310011 and by AMED-Project for Elucidating and Controlling Mechanisms of Aging and Longevity to M.M under Grant Number JP21gm5010001. This work was also supported by grants from the Japan Society for the Promotion of Science to F.O. under Grant Number 19H03367, 20H05726, and 22H02769, and to M.M. under Grant Numbers 16H06385, 21H04774, 21K19206, and 23H04766.
Funding Information:
The authors would like to acknowledge Kyoto Stock Center, National Institute of Genetics, Vienna Drosophila Resource Center, and Bloomington Drosophila Stock Center for reagents. We thank Takao Fujisawa, Yoriko Akuzawa, and all the members of Miura’s laboratory and Obata’s laboratory for technical assistance and critical advice. We thank Sa Kan Yoo and Scott Pletcher for the critical reading of the manuscript. This work was supported by AMED-PRIME to F.O. under Grant Number JP20gm6310011 and by AMED-Project for Elucidating and Controlling Mechanisms of Aging and Longevity to M.M under Grant Number JP21gm5010001. This work was also supported by grants from the Japan Society for the Promotion of Science to F.O. under Grant Number 19H03367, 20H05726, and 22H02769, and to M.M. under Grant Numbers 16H06385, 21H04774, 21K19206, and 23H04766.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85178929808
U2 - 10.1038/s41467-023-43550-2
DO - 10.1038/s41467-023-43550-2
M3 - Article
C2 - 38052797
AN - SCOPUS:85178929808
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7832
ER -