{
  "abstract": "Introduction: Epidermal aging is characterized by progressive structural alterations, including reduced keratinocyte density, altered cellular morphology, and widened intercellular spacing (ICS). Reflectance confocal microscopy (RCM) combined with artificial intelligence (AI)-assisted image analysis enables non-invasive quantification of these changes in vivo. This secondary analysis of RCM images reported in a previously published randomized split-face clinical trial aimed to identify quantitative morphometric features associated with chronological aging and to evaluate their modulation following topical application of the transforming growth factor-beta (TGF-β) mimetic XEP™-716 Miniprotein™ (Activen SA, Lausanne. Switzerland).\n\nMethods: Previously acquired baseline RCM images from 49 women (age 40–60 years) were analyzed for associations with chronological age. Treatment effects were assessed in 25 women from the 2.5% arm of a 56-day randomized, double-blind, split-face study comparing XEP™-716 Miniprotein™ 2.5% with vehicle. AI-assisted image analysis quantified keratinocyte density, cellular circularity, and ICS in the stratum granulosum (SG) and the stratum spinosum (SS). Cells with circularity ≤ 0.439 were classified as low-circularity cells and those ≥ 0.440 circularity as morphologically normal. Treatment effects were assessed using linear mixed-effects models.\n\nResults: Stratum granulosum total and normal keratinocyte densities were nominally significantly associated with age (p = 0.015 and p = 0.023, respectively). Compared with vehicle, XEP™-716 Miniprotein™ used at 2.5% was associated with nominally significant increases in normal keratinocyte density (p = 0.028) and the circularity of low-circularity cells (p = 0.018), and with decreases in ICS thickness (p = 0.030) and low-circularity cell density (p = 0.044) in the SG. In the SS, there was a non-significant trend towards reduced low-circularity cell density (p = 0.075).\n\nConclusion: Artificial intelligence-assisted quantitative RCM can identify age-associated epidermal morphometric features, predominantly in the SG, and detect their modulation following topical treatment. XEP™-716 Miniprotein™ at 2.5% showed consistent treatment-associated changes across several morphometric parameters with nominal statistical significance. These exploratory findings warrant prospective validation against molecular senescence markers and functional barrier measurements.",
  "abstract_shown": true,
  "affiliations": [
    "Activen, Epalinges, Switzerland",
    "Remora Biotech, Epalinges, Switzerland",
    "Stella Polaris Europe, Paris, France",
    "CILIA Consulting, Paris, France",
    "PhD Trials®, Lisbon, Portugal",
    "TS-Consulting, Olivet, France"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hanane Chajra",
      "orcid": "0000-0001-6751-6659"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicolas Rayroux"
    },
    {
      "affs": [
        2
      ],
      "name": "Corinne Granger",
      "orcid": "0000-0001-5117-448X"
    },
    {
      "affs": [
        3
      ],
      "name": "Lionel Breton",
      "orcid": "0009-0003-4912-3263"
    },
    {
      "affs": [
        4
      ],
      "name": "Pedro Contreiras PInto",
      "orcid": "0000-0002-5723-0750"
    },
    {
      "affs": [
        5
      ],
      "name": "Thibaut Saguet",
      "orcid": "0000-0003-1274-1773"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Marc Le Doussal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cpmhfhqs41jrd.bib",
  "cited_by": 0,
  "doi": "10.1007/s13555-026-01945-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696636/",
  "id": "cpmhfhqs41jrd",
  "issns": [
    "2193-8210",
    "2190-9172"
  ],
  "landing_url": "https://doi.org/10.1007/s13555-026-01945-1",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Brief Report"
    ],
    [
      "lcc",
      "RL1-803"
    ],
    [
      "openalex",
      "2708|Skin Protection and Aging"
    ]
  ],
  "openalex": "W7215054041",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s13555-026-01945-1.pdf",
  "pmcid": "PMC13696636",
  "pmid": "42821227",
  "published": "2026-10-01",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/cpmhfhqs41jrd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:57Z",
      "native_id": "PMC13696636",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s13555-026-01945-1"
    },
    {
      "first_seen": "2026-10-30T13:45:39Z",
      "native_id": "e9798057eb8e4c6bacbff8be5cf30bc7",
      "source": "doaj",
      "url": "https://doi.org/10.1007/s13555-026-01945-1"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2708|Skin Protection and Aging",
      "subfield": "general"
    }
  ],
  "title": "AI-Assisted Quantitative Reflectance Confocal Microscopy Reveals Modulation of Senescence-Associated Epidermal Morphometric Features by a Topical TGF-β Mimetic, XEP™-716 Miniprotein™",
  "title_text": "AI-Assisted Quantitative Reflectance Confocal Microscopy Reveals Modulation of Senescence-Associated Epidermal Morphometric Features by a Topical TGF-β Mimetic, XEP™-716 Miniprotein™",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:39Z",
  "url": "https://research.draconitic.com/paper/cpmhfhqs41jrd",
  "venue": "Dermatology and Therapy",
  "versions": []
}