{
  "abstract": "Senescent cells drive tissue dysfunction through the senescence-associated secretory phenotype (SASP). We uncovered a central role for mitochondria in the epigenetic regulation of the SASP, where mitochondrial-derived metabolites, specifically citrate and acetyl-CoA, fuel histone acetylation at SASP gene loci, promoting their expression. We identified the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY) as critical for this process. Inhibiting these pathways selectively suppresses SASP without affecting cell cycle arrest, highlighting their potential as therapeutic targets for age-related inflammation. Notably, SLC25A1 inhibition reduces systemic inflammation and extends healthspan in aged mice, establishing mitochondrial metabolism as pivotal to the epigenetic control of aging.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA",
    "Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA",
    "Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK",
    "MRC Laboratory of Medical Sciences (LMS), London, UK",
    "Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA",
    "Division of Experimental Pathology, Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN, USA",
    "Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA",
    "Department of Oncology, Division of Oncology Research, Mayo Clinic, Rochester, MN, USA",
    "Molecular Pharmacology and Experimental Therapeutics Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA",
    "Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA",
    "Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA",
    "Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA",
    "School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK",
    "Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA",
    "Eberhard Karls University Tuebingen, Tuebingen, Germany",
    "Robert Bosch Center for Tumor Diseases, Stuttgart, Germany",
    "Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA",
    "Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. padams@sbpdiscovery.org",
    "Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. passos.joao@mayo.edu",
    "Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA. passos.joao@mayo.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hélène Martini",
      "orcid": "0000-0001-8789-4585"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jodie Birch",
      "orcid": "0000-0003-1727-1125"
    },
    {
      "affs": [
        4
      ],
      "name": "Francisco Madeira Marques",
      "orcid": "0000-0001-7521-6955"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Stella G. Victorelli",
      "orcid": "0000-0001-5573-8019"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anthony B. Lagnado",
      "orcid": "0000-0002-9380-5179"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nicholas Pirius"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ana Catarina Franco",
      "orcid": "0000-0001-6730-7021"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gung Lee",
      "orcid": "0000-0002-0223-7955"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yeaeun Han",
      "orcid": "0000-0003-1122-3691"
    },
    {
      "affs": [
        1
      ],
      "name": "Jennifer L. Rowsey",
      "orcid": "0009-0005-0677-7907"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Wazim Mohammed Ismail",
      "orcid": "0000-0002-1782-7296"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Amelia Mazzone",
      "orcid": "0000-0001-6236-6962"
    },
    {
      "affs": [
        7
      ],
      "name": "Tianna Espe"
    },
    {
      "affs": [
        7
      ],
      "name": "Taro Hitosugi",
      "orcid": "0000-0002-2898-6831"
    },
    {
      "affs": [
        8
      ],
      "name": "Ya Li",
      "orcid": "0000-0001-7347-386X"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Alexander M. Washington",
      "orcid": "0000-0002-9804-3329"
    },
    {
      "affs": [
        11
      ],
      "name": "Aaron P. Havas",
      "orcid": "0000-0003-4291-8015"
    },
    {
      "affs": [
        11
      ],
      "name": "Rabi Murad",
      "orcid": "0009-0004-5297-8307"
    },
    {
      "affs": [
        11
      ],
      "name": "Xue Lei",
      "orcid": "0000-0001-9647-3782"
    },
    {
      "affs": [
        11
      ],
      "name": "Rebecca A. Porritt",
      "orcid": "0000-0002-0973-5092"
    },
    {
      "affs": [
        12
      ],
      "name": "Oliver D.K. Maddocks",
      "orcid": "0000-0002-5551-9091"
    },
    {
      "affs": [
        13
      ],
      "name": "Jair Machado Espíndola‐Netto",
      "orcid": "0000-0003-0387-5059"
    },
    {
      "affs": [
        14,
        15,
        1
      ],
      "name": "Dominik Saul",
      "orcid": "0000-0002-0673-3710"
    },
    {
      "affs": [
        1
      ],
      "name": "Sundeep Khosla",
      "orcid": "0000-0002-2936-4372"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Diana Jurk",
      "orcid": "0000-0003-4486-0857"
    },
    {
      "affs": [
        16,
        9
      ],
      "name": "Enis Kostallari",
      "orcid": "0000-0002-7138-5580"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Alexandre Gaspar‐Maia",
      "orcid": "0000-0001-8528-5575"
    },
    {
      "affs": [
        17
      ],
      "name": "Peter D. Adams",
      "orcid": "0000-0002-0684-1770"
    },
    {
      "affs": [
        18,
        19
      ],
      "name": "João F. Passos",
      "orcid": "0000-0001-8765-1890"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0zzzy4540m2xf.bib",
  "cited_by": 16,
  "doi": "10.1038/s41586-026-10791-2",
  "fulltext_url": null,
  "id": "0zzzy4540m2xf",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10791-2",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Telomeres, Telomerase, and Senescence"
    ],
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7171743616",
  "pdf_url": null,
  "pmcid": "PMC11643321",
  "pmid": "39678326",
  "published": "2026-07-29",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/0zzzy4540m2xf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:56Z",
      "native_id": "W7171743616",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10791-2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Telomeres, Telomerase, and Senescence",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "openalex:2737|Telomeres, Telomerase, and Senescence",
      "subfield": "physiology"
    }
  ],
  "title": "Mitochondrial metabolism and epigenetic crosstalk drive SASP",
  "title_text": "Mitochondrial metabolism and epigenetic crosstalk drive SASP",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/0zzzy4540m2xf",
  "venue": "Nature",
  "versions": []
}