Authors
Koji Masumura, Sayaka Kawasaki, Mayu Tsutsumi, Hiiro Yamashita, Muneyoshi Kanai, Haruto Nakajo, Wakaba Yagi, Shoma Katsunoi, Kaori Yoneyama, Miyuki Kawano-Kawada, Takayuki Sekito, Takafumi Ogawa, Tomoyoshi Soga, Masaki Mizunuma
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 42. Pages e2621286123. Oct 20, 2026. Epub Oct 16, 2026.
Abstract
S-adenosyl-L-methionine (SAM) is a fundamental methyl donor; however, the physiological role of its byproduct and competitive inhibitor, S-adenosyl-L-homocysteine (SAH), remains unclear. Here, we show that transient reactive oxygen species (ROS) production triggered by SAH during the early logarithmic phase mimics partial SAH hydrolase inhibition, extending the yeast chronological lifespan (CLS) through a hormetic mechanism. This study reveals that the dual nature of ROS in aging is determined by the specific degree of SAH hydrolase activity. We identified the adenosine 5'-triphosphate-binding cassette (ABC) transporter Ybt1 as a key downstream effector of SAH. Ybt1 localizes to the vacuolar membrane and facilitates the sequestration of SAM from the cytosol into the vacuole. Notably, YBT1 overexpression extends CLS, mimicking SAH effects through an integrated pathway involving target of rapamycin complex 1 downregulation, autophagy, and adenosine 5'-monophosphate-activated protein kinase activation. Our findings establish that SAH acts as a metabolic signal coupling nutrient and energy availability to longevity via Ybt1, defining an adaptive/hormetic response for lifespan regulation in yeast.
PMID:
42886693
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.
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