{
  "abstract": "Aging-associated inflammation, or 'inflammaging\" is a driver of multiple age-associated diseases. Cyclic GMP-AMP Synthase (cGAS) is a cytosolic DNA sensor that functions to activate interferon response upon detecting viral DNA in the cytoplasm. cGAS contributes to inflammaging by responding to endogenous signals such as damaged DNA or LINE1 (L1) cDNA which forms in aged cells. While cGAS knockout mice are viable their aging has not been examined. Unexpectedly, we found that cGAS knockout mice exhibit accelerated aging phenotype associated with induction of inflammation. Transcription of L1 elements was increased in both cGAS knockout mice and in cGAS siRNA knockdown cells associated with high levels of cytoplasmic L1 DNA and expression of ORF1 protein. Cells from cGAS knockout mice showed increased chromatin accessibility and decreased DNA methylation on L1 transposons. Stimulated emission depletion microscopy (STED) showed that cGAS forms nuclear condensates that co-localize with H3K9me3 heterochromatin marks, and H3K9me3 pattern is disrupted in cGAS knockout cells. Taken together these results suggest a previously undescribed role for cGAS in maintaining heterochromatin on transposable elements. We propose that loss of cGAS leads to loss of chromatin organization, de-repression of transposable elements and induction of inflammation resulting in accelerated aging.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biology, University of Rochester, Rochester, NY, USA",
    "Translational Biomedical Sciences Program, University of Rochester Medical Center, Rochester, NY, USA",
    "University of Rochester Medical Center",
    "University of Rochester",
    "Department of Surgical Pathology, University of Rochester Medical Center, Rochester, NY, USA",
    "Brown University",
    "Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide, Seville, Spain",
    "Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA",
    "Department of Biology, University of Rochester, Rochester, NY, USA. andrei.seluanov@rochester.edu",
    "Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA. andrei.seluanov@rochester.edu",
    "Department of Biology, University of Rochester, Rochester, NY, USA. vera.gorbunova@rochester.edu",
    "Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA. vera.gorbunova@rochester.edu",
    "Translational Biomedical Sciences Program, University of Rochester Medical Center, Rochester, NY, USA. vera.gorbunova@rochester.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "John C. Martinez",
      "orcid": "0000-0003-0040-8519"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Francesco Morandini",
      "orcid": "0000-0003-1040-8539"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Cheyenne Rechsteiner",
      "orcid": "0000-0003-1527-2319"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Lucinda Fitzgibbons"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Natasha Sieczkiewicz"
    },
    {
      "affs": [
        4,
        3
      ],
      "name": "Xiaoyan Liao",
      "orcid": "0000-0002-5052-0632"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Weijie He"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Sung Jae Bae"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Michael E. Meadow",
      "orcid": "0000-0003-0766-7863"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Eric C. Hillpot"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Joseph Cutting"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Victoria Paige",
      "orcid": "0009-0009-4686-6452"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Max Zacher",
      "orcid": "0000-0003-0377-7221"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Seyed Ali Biashad",
      "orcid": "0000-0001-9591-7687"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew A. Simon",
      "orcid": "0000-0002-4395-0917"
    },
    {
      "affs": [
        6
      ],
      "name": "Inés Muela‐Zarzuela",
      "orcid": "0000-0002-7240-8334"
    },
    {
      "affs": [
        6
      ],
      "name": "Mario David Cordero",
      "orcid": "0000-0003-0151-3644"
    },
    {
      "affs": [
        7
      ],
      "name": "Martin S. Taylor",
      "orcid": "0000-0001-5824-142X"
    },
    {
      "affs": [
        7
      ],
      "name": "John M. Sedivy",
      "orcid": "0000-0001-9363-4253"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Andrei Seluanov",
      "orcid": "0000-0003-3400-538X"
    },
    {
      "affs": [
        10,
        11,
        12
      ],
      "name": "Vera A. Gorbunova",
      "orcid": "0000-0001-8979-0333"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/645w1mgp88b02.bib",
  "cited_by": 17,
  "doi": "10.1038/s43587-026-01206-y",
  "fulltext_url": null,
  "id": "645w1mgp88b02",
  "issns": [
    "2662-8465"
  ],
  "landing_url": "https://doi.org/10.1038/s43587-026-01206-y",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
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  "pdf_url": "https://www.nature.com/articles/s43587-026-01206-y.pdf",
  "pmcid": "PMC11482887",
  "pmid": "39416083",
  "published": "2026-08-25",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/645w1mgp88b02.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
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      "url": "https://doi.org/10.1038/s43587-026-01206-y"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "cGAS-deficient mice display premature aging associated with derepression of LINE1 elements and inflammation",
  "title_text": "cGAS-deficient mice display premature aging associated with derepression of LINE1 elements and inflammation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/645w1mgp88b02",
  "venue": "Nature Aging",
  "versions": []
}