{
  "abstract": "Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) resets epigenetic age, creating a major challenge for modeling age-associated cellular states and limiting the use of iPSCs in aging research beyond the genetic component. Recent work has shown that healthy organoids can re-accumulate age-associated epigenetic states over extended culture; whether disease-associated genetic states can directionally reshape these trajectories after reprogramming remains unknown. Here, we present a reproducible, in-vitro approach to re-establish epigenetic aging trajectories using iPSC-derived organoid systems, as quantified by multiple epigenetic clock models. We first demonstrate that epigenetic age progressively increases with serial passaging in a lung organoid model (alveolospheres). We then show that disease-associated mutations in multiple models drive additional, cell-intrinsic shifts in epigenetic age, implicating disease state as an independent modulator of epigenetic clocks. Together, these findings reinforce that iPSC-derived organoids recapitulate epigenetic aging trajectories over time, while highlighting disease state as a potent and potentially tractable modulator of epigenetic age in vitro. By enabling more faithful modeling of age-associated cellular states, this approach expands the utility of iPSC-based systems for dissecting the molecular mechanisms that regulate human aging.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Regenerative Medicine (CReM) of Boston University, and Boston Medical Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "N. J. Skvir"
    },
    {
      "name": "T. W. Dowrey"
    },
    {
      "name": "S. F. Cranston"
    },
    {
      "name": "E. MacDonald"
    },
    {
      "name": "R. Giadone"
    },
    {
      "name": "D. Jones"
    },
    {
      "name": "C. S. Golden"
    },
    {
      "name": "B. Pate"
    },
    {
      "name": "M. Labott"
    },
    {
      "name": "M. A. Serrano"
    },
    {
      "name": "K.-D. Alysandratos"
    },
    {
      "name": "K. Vanuytsel"
    },
    {
      "affs": [
        0
      ],
      "name": "G. J. Murphy"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bwnwmas7q2dxk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755445",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755445v1.full",
  "id": "bwnwmas7q2dxk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755445v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|Pluripotent Stem Cells Research"
    ]
  ],
  "openalex": "W7220427506",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755445v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bwnwmas7q2dxk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:58Z",
      "native_id": "10.64898/2026.09.30.755445",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755445v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Disease-associated mutations directionally modulate epigenetic age in iPSC-derived tissues",
  "title_text": "Disease-associated mutations directionally modulate epigenetic age in iPSC-derived tissues",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:58Z",
  "url": "https://research.draconitic.com/paper/bwnwmas7q2dxk",
  "venue": "bioRxiv",
  "versions": []
}