{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:50:31Z","timestamp":1787323831536,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3404400"],"award-info":[{"award-number":["2023YFC3404400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Disentangling intrinsic (chronological) skin ageing from ultraviolet\u2010driven photoaging remains challenging because most human skin single\u2010cell studies are biassed towards sun\u2010exposed sites and non\u2010genital anatomy. Here, we profiled histologically normal human penile skin, a typically UV\u2010shielded mucocutaneous niche, to characterise ageing\u2010associated remodelling in a specialised cutaneous microenvironment. We analysed 137\u2009880 cells from 13 healthy male donors (13\u201363\u2009years) and identified 12 major cell types. Donor\u2010aware compositional profiling revealed pronounced age\u2010associated stromal depletion, driven by progressive loss of fibroblasts and pericyte\/vascular smooth muscle cells. Whole\u2010skin pseudo\u2010bulk modelling across continuous age captured broad transcriptional drift towards senescence\u2010 and inflammation\u2010related programmes alongside reduced extracellular matrix organisation and Wnt\u2010associated maintenance pathways. Cell type\u2010resolved pseudo\u2010bulk analyses localised the strongest age\u2010associated changes to stromal lineages. In fibroblasts, unsupervised temporal module analysis indicated a shift from matrix\u2010supportive\/regenerative programmes towards a pro\u2010inflammatory, senescence\u2010associated secretory phenotype\u2010like state. Cross\u2010compartment overlap further identified a 21\u2010gene core module shared across epidermal, stromal, and immune compartments in older donors, consistent with coordinated tissue\u2010wide remodelling. Together, these findings nominate stromal attrition and inflammatory fibroblast reprogramming as central features of ageing in human penile skin and provide a site\u2010specific framework for distinguishing conserved intrinsic ageing modules from niche\u2010shaped execution mechanisms. This UV\u2010shielded genital reference offers a complementary baseline for interpreting intrinsic ageing signals across anatomically diverse skin sites.<\/jats:p>","DOI":"10.1111\/exd.70322","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:09:08Z","timestamp":1783490948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast State Remodelling and Stromal Depletion Shape the Ageing Microenvironment of Human Penile Skin"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-3076","authenticated-orcid":false,"given":"Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center  Beijing China"},{"name":"Department of Dermatology and Venereology Peking University First Hospital  Beijing China"},{"name":"Beijing Advanced Center of Cellular Homeostasis and Aging\u2010Related Diseases, Institute of Advanced Clinical Medicine, Peking University  Beijing China"},{"name":"Biomedical Engineering Department Institute of Advanced Clinical Medicine, Peking University  Beijing China"},{"name":"State Key Laboratory of Molecular Oncology, Peking University International Cancer Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology Peking University First Hospital  Beijing China"},{"name":"National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses  Beijing 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