S-adenosyl-L-homocysteine extends lifespan through methionine restriction effects

Takafumi Ogawa, Koji Masumura, Yuki Kohara, Muneyoshi Kanai, Tomoyoshi Soga, Yoshikazu Ohya, T. Keith Blackwell, Masaki Mizunuma

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Methionine restriction (MetR) can extend lifespan and delay the onset of aging-associated pathologies in most model organisms. Previously, we showed that supplementation with the metabolite S-adenosyl-L-homocysteine (SAH) extends lifespan and activates the energy sensor AMP-activated protein kinase (AMPK) in the budding yeast Saccharomyces cerevisiae. However, the mechanism involved and whether SAH can extend metazoan lifespan have remained unknown. Here, we show that SAH supplementation reduces Met levels and recapitulates many physiological and molecular effects of MetR. In yeast, SAH supplementation leads to inhibition of the target of rapamycin complex 1 (TORC1) and activation of autophagy. Furthermore, in Caenorhabditis elegans SAH treatment extends lifespan by activating AMPK and providing benefits of MetR. Therefore, we propose that SAH can be used as an intervention to lower intracellular Met and confer benefits of MetR.

本文言語English
論文番号e13604
ジャーナルAging Cell
21
5
DOI
出版ステータスPublished - 2022 5月

ASJC Scopus subject areas

  • 加齢科学
  • 細胞生物学

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