{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Healthy Aging, Unit of Biotechnology, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.",
    "Brewing Microbiology Division, National Research Institute of Brewing, Higashi-Hiroshima 739-0046, Japan.",
    "Laboratory of Molecular Physiology and Genetics, Faculty of Agriculture, Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan.",
    "Research and Development Bureau, Saitama University, Saitama 338-8570, Japan.",
    "Division of Cell-Free Sciences, Proteo-Science Center, Ehime University, Matsuyama 790-8577, Japan.",
    "Division of Genetic Research Support, the Advanced Research Support Center, Ehime University, Matsuyama 790-8566, Japan.",
    "Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan.",
    "Human Biology-Microbiome-Quantum Research Center, Keio University, Tokyo 160-8582, Japan.",
    "Hiroshima Research Center for Healthy Aging, Hiroshima University, Higashi-Hiroshima 739-8530, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Koji Masumura",
      "orcid": "0009-0000-6742-0809"
    },
    {
      "affs": [
        0
      ],
      "name": "Sayaka Kawasaki",
      "orcid": "0009-0005-3654-2973"
    },
    {
      "affs": [
        0
      ],
      "name": "Mayu Tsutsumi"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiiro Yamashita"
    },
    {
      "affs": [
        1
      ],
      "name": "Muneyoshi Kanai"
    },
    {
      "affs": [
        2
      ],
      "name": "Haruto Nakajo"
    },
    {
      "affs": [
        2
      ],
      "name": "Wakaba Yagi"
    },
    {
      "affs": [
        2
      ],
      "name": "Shoma Katsunoi"
    },
    {
      "affs": [
        3
      ],
      "name": "Kaori Yoneyama"
    },
    {
      "affs": [
        2,
        4,
        5
      ],
      "name": "Miyuki Kawano-Kawada",
      "orcid": "0000-0002-1168-9291"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Takayuki Sekito"
    },
    {
      "affs": [
        0
      ],
      "name": "Takafumi Ogawa",
      "orcid": "0000-0001-8673-8804"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Tomoyoshi Soga",
      "orcid": "0000-0001-9502-2509"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Masaki Mizunuma",
      "orcid": "0000-0002-1531-1763"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d6wsvpp4qws4a.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2621286123",
  "fulltext_url": "https://europepmc.org/articles/PMC13684291",
  "id": "d6wsvpp4qws4a",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://europepmc.org/article/MED/42886693",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7222651658",
  "pdf_url": "https://europepmc.org/articles/PMC13684291?pdf=render",
  "pmcid": "PMC13684291",
  "pmid": "42886693",
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d6wsvpp4qws4a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42886693",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42886693"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "S-adenosyl-L-homocysteine triggers an adaptive response that extends lifespan through the YBT1 ABC transporter.",
  "title_text": "S-adenosyl-L-homocysteine triggers an adaptive response that extends lifespan through the YBT1 ABC transporter.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/d6wsvpp4qws4a",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}