{
  "abstract": "Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature ageing disease that predominantly affects tissues with high regenerative capacity. Although the intestine is the most rapidly self-renewing tissue of adult mammals, it has so far been considered only as a source of microbiota-derived disturbances in progeria, and whether the intestinal epithelium is itself a target of progerin remains unknown. Here, using the LmnaG609G/G609G and LmnaG609G/+ mouse models, intestinal organoids and single-cell RNA sequencing, we show that progerin is expressed in colonic enterocytes and in SMA+ subepithelial myofibroblasts of the stem-cell niche. Heterozygous progeria mice develop increased intestinal permeability from 30 weeks of age, reaching levels reported in physiologically aged (>20-month-old) mice. Progeria-derived intestinal organoids display reduced mitochondrial oxygen consumption, a compensatory increase in glycolysis and impaired crypt budding. Single-cell transcriptomics of the colonic epithelium and lamina propria revealed that, while lineage composition is preserved, progerin induces a coordinated reprogramming characterised by repression of oxidative phosphorylation and mitochondrial quality-control genes, including Nod2, activation of interferon, TNF-NF-kB and innate defence programs, and up-regulation of RNA-processing and chromatin-associated pathways. Trajectory analysis showed that progeria absorptive enterocytes selectively fail to reach terminal differentiation states and retain progenitor-like WNT, NOTCH and EGFR signatures, while lacking the mitochondrial programs required for maturation. Together, these findings identify the intestinal epithelium as a cell-intrinsic target of progerin and support a model in which mitochondrial insufficiency stalls absorptive enterocyte maturation and weakens the intestinal barrier, recapitulating, prematurely, key features of colon ageing.",
  "abstract_shown": true,
  "affiliations": [
    "Institut Necker Enfants Malades"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "C. Reisacher"
    },
    {
      "name": "M. Singh"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Arbibe"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ejyezvvm2k6z4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.758066",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758066v1.full",
  "id": "ejyezvvm2k6z4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758066v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pathology"
    ],
    [
      "openalex",
      "1312|Nuclear Structure and Function"
    ]
  ],
  "openalex": "W7221818642",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758066v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ejyezvvm2k6z4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:48Z",
      "native_id": "10.64898/2026.10.09.758066",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.758066v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nuclear Structure and Function",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Progerin disrupts intestinal epithelial homeostasis by impairing mitochondrial metabolism and absorptive enterocyte maturation",
  "title_text": "Progerin disrupts intestinal epithelial homeostasis by impairing mitochondrial metabolism and absorptive enterocyte maturation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:48Z",
  "url": "https://research.draconitic.com/paper/ejyezvvm2k6z4",
  "venue": "bioRxiv",
  "versions": []
}