{
  "abstract": "Ageing is accompanied by heterogeneous changes in tissue structure, cellular composition, and microenvironments, yet how these changes are reflected in routine human histology remains poorly understood. Here, we introduce a histology-first, multi-scale digital pathology framework to study human colon ageing using hematoxylin and eosin (H&E) whole-slide images from clinically normal colon biopsies. The framework combines pathology foundation-model patch embeddings, attention-based multiple-instance learning, cell-level morphometric profiling, and prototype-based tissue compartmentalization. We show that chronological age can be predicted from normal colon tissue using mesoscopic representations derived from pathology foundation-model patch embeddings and attention-based multiple-instance learning. Incorporating cell-type-level morphometric features further improves prediction and refines the spatial allocation of model attention. By integrating attention maps with prototype-defined tissue compartments, we identify localized age-associated differences within stromal, epithelial, and lymphoid mucosal niches. Finally, we show that prediction discordant cases exhibit cellular profiles shifted toward the model-assigned age group, suggesting that some apparent model errors may reflect tissue-level age discordance beyond chronological age. Together, these findings show that routine H&E histology captures spatially localized signatures of normal human colon ageing and provides a scalable framework for linking tissue morphology with biological ageing state.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "G. Altshuler"
    },
    {
      "name": "C. Teper"
    },
    {
      "name": "Y. Barak"
    },
    {
      "name": "S. Aviel-Ronen"
    },
    {
      "name": "A. Loebel"
    },
    {
      "name": "I. Barshack"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5qww4872hdxd6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.20.760359",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760359v1.full",
  "id": "5qww4872hdxd6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760359v1",
  "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",
      "pathology"
    ],
    [
      "openalex",
      "1702|AI in cancer detection"
    ]
  ],
  "openalex": "W7223455793",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760359v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5qww4872hdxd6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:31Z",
      "native_id": "10.64898/2026.10.20.760359",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760359v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pathology",
      "subfield": "general"
    }
  ],
  "title": "Multi-scale histology reveals localized ageing signatures in normal human colon",
  "title_text": "Multi-scale histology reveals localized ageing signatures in normal human colon",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:31Z",
  "url": "https://research.draconitic.com/paper/5qww4872hdxd6",
  "venue": "bioRxiv",
  "versions": []
}