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

Autor:	Takafumi Ogawa, Koji Masumura, Yuki Kohara, Muneyoshi Kanai, Tomoyoshi Soga, Yoshikazu Ohya, T. Keith Blackwell, Masaki Mizunuma
Rok vydání:	2022
Předmět:	Aging Methionine Longevity Animals Saccharomyces cerevisiae Cell Biology AMP-Activated Protein Kinases S-Adenosylhomocysteine
Zdroj:	Aging Cell. 21
ISSN:	1474-9726 1474-9718
DOI:	10.1111/acel.13604
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e02952bd5be1cf0ac2a00e781c97f1f6 https://doi.org/10.1111/acel.13604 Zobrazit plný text záznamu