Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK

Takafumi Ogawa, Ryohei Tsubakiyama, Muneyoshi Kanai, Tetsuya Koyama, Tsutomu Fujii, Haruyuki Iefuji, Tomoyoshi Soga, Kazunori Kume, Tokichi Miyakawa, Dai Hirata, Masaki Mizunuma

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15 Citations (Scopus)

Abstract

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulating S-adenosyl-L-methionine (AdoMet) synthesis extended the lifespan of the budding yeast Saccharomyces cerevisiae. The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is the S. cerevisiae ortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed that S-adenosyl-L-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

Original languageEnglish
Pages (from-to)11913-11918
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number42
DOIs
Publication statusPublished - 2016 Oct 18

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Keywords

  • AMP-activated protein kinase
  • Calorie restriction
  • S-adenosyl-L-homocysteine
  • S-adenosyl-L-methionine
  • Yeast

ASJC Scopus subject areas

  • General

Cite this

Ogawa, T., Tsubakiyama, R., Kanai, M., Koyama, T., Fujii, T., Iefuji, H., Soga, T., Kume, K., Miyakawa, T., Hirata, D., & Mizunuma, M. (2016). Stimulating S-adenosyl-L-methionine synthesis extends lifespan via activation of AMPK. Proceedings of the National Academy of Sciences of the United States of America, 113(42), 11913-11918. https://doi.org/10.1073/pnas.1604047113