S‐adenosyl‐L‐homocysteine extends lifespan through methionine restriction effects. Issue 5 (7th April 2022)

• Record Type: Journal Article
• Authors: Ogawa, Takafumi; Masumura, Koji; Kohara, Yuki; Kanai, Muneyoshi; Soga, Tomoyoshi; Ohya, Yoshikazu; Blackwell, T. Keith; Mizunuma, Masaki
• Is Part Of: Aging cell. Volume 21:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-07
• Subjects: Caenorhabditis elegans -- methionine restriction (MetR) -- Saccharomyces cerevisiae -- S‐adenosyl‐L‐homocysteine (SAH) -- S‐adenosyl‐L‐methionine (SAM); Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13604
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: 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. Abstract : A model depicting how SAH extends lifespan. The intake of SAH reduces intracellular Met and induces benefits associated with MetR in yeast and nematodes. SAH treatment extended lifespan via inhibition of mTORC1 and activation of autophagy and AMPK.