{
  "abstract": "Biological aging drives cellular dysfunction and human disease, yet studying human aging dynamics remains challenging due to limited experimental platforms. Here we show that long-term post-mitotic culture of human fibroblasts recapitulates and accelerates features of in vivo aging. Longitudinal paired transcriptomic and epigenetic analyses of four female fibroblast lines revealed that in vitro aging reflects key signatures of in vivo primary fibroblast aging. Direct neuronal conversion of in vitro-aged fibroblasts preserved biological age, enabling pseudo-longitudinal modeling of neuronal aging through direct reprogramming. Single-cell transcriptomics of in vitro-aging fibroblasts revealed a time-dependent increase in age-heterogeneity, consistent with the previously reported age-associated heterogeneity driven by the variable loss of transcriptional programs in vivo. Using this accelerated aging platform, we evaluated anti-aging compounds: Metformin broadly attenuated transcriptomic and epigenetic aging, while Rapamycin showed limited efficacy. These findings align with pre-clinical evidence, providing a platform to evaluate and predict therapeutic anti-aging compound efficacy at molecular resolution. This system advances our understanding of aging mechanisms and facilitates the development of interventions against age-related diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosciences, University of California San Diego, La Jolla, California, USA.",
    "Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, USA.",
    "Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA.",
    "Institute for Molecular Biology, University of Innsbruck, Innsbruck, Austria.",
    "Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Tyrol, Austria.",
    "Department of Biochemistry and Genetics of Aging, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Tyrol, Austria.",
    "Division of Psychiatry I, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Innsbruck, Tyrol, Austria."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Larissa Traxler"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lukas Karbacher",
      "orcid": "0000-0001-5739-2605"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Oliver Borgogno",
      "orcid": "0009-0004-4402-0879"
    },
    {
      "affs": [
        0
      ],
      "name": "Taylor Ozbun"
    },
    {
      "affs": [
        0
      ],
      "name": "Kylie Champion",
      "orcid": "0009-0005-2361-8940"
    },
    {
      "affs": [
        3
      ],
      "name": "Anna Smaling"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lucia Zhou-Yang",
      "orcid": "0000-0003-4186-6129"
    },
    {
      "affs": [
        2
      ],
      "name": "Joseph R Herdy",
      "orcid": "0000-0002-8636-8134"
    },
    {
      "affs": [
        3
      ],
      "name": "Lena Böhnke",
      "orcid": "0000-0002-8614-6603"
    },
    {
      "affs": [
        4
      ],
      "name": "Barbara C Böckle"
    },
    {
      "affs": [
        2
      ],
      "name": "Fred H Gage",
      "orcid": "0000-0002-0938-4106"
    },
    {
      "affs": [
        5
      ],
      "name": "Hildegard I D Mack"
    },
    {
      "affs": [
        6
      ],
      "name": "Michaela Defrancesco",
      "orcid": "0000-0001-9613-9485"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jerome Mertens",
      "orcid": "0000-0002-4291-4121"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/644fmdz2jrpk9.bib",
  "cited_by": 0,
  "doi": "10.1111/acel.70796",
  "fulltext_url": "https://europepmc.org/articles/PMC13724222",
  "id": "644fmdz2jrpk9",
  "issns": [
    "1474-9718",
    "1474-9726"
  ],
  "landing_url": "https://europepmc.org/article/MED/42967595",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W4408955703",
  "pdf_url": "https://europepmc.org/articles/PMC13724222?pdf=render",
  "pmcid": "PMC13724222",
  "pmid": "42967595",
  "published": "2026-11-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/644fmdz2jrpk9.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42967595",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42967595"
    },
    {
      "first_seen": "2026-11-04T12:22:43Z",
      "native_id": "PMC13724222",
      "source": "pmc",
      "url": "https://doi.org/10.1111/acel.70796"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "Long-Term Post-Mitotic Culture of Human Fibroblasts Recapitulates and Accelerates Features of In Vivo Aging and Enables Dynamic Testing of Anti-Aging Compounds.",
  "title_text": "Long-Term Post-Mitotic Culture of Human Fibroblasts Recapitulates and Accelerates Features of In Vivo Aging and Enables Dynamic Testing of Anti-Aging Compounds.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:54Z",
  "url": "https://research.draconitic.com/paper/644fmdz2jrpk9",
  "venue": "Aging cell",
  "versions": []
}