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These two clocks and the Horvath \u2018Skin and Blood\u2019 epigenetic clock were tested for association with chronological age and, whilst controlling for chronological age (age acceleration), sun-exposure parameters and skin gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exogenous Skin clock ages were significantly (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001) older in both epidermal (n=24) and cultured fibroblast (n=8) sun-exposed arm samples than in donor matched sun-protected samples. Exogenous Skin clock age acceleration was significantly correlated (Rho = 0.18,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004) with sun-seeking behaviour and mRNA levels (202 genes had q &lt; 0.05) in whole skin abdomen samples (n=364); the latter was consistent with sun-exposed versus sun-protected older arm mRNA differences (n=12 donors). In 44 facial skin swabs, exogenous age acceleration was also significantly correlated with facial photodamage grading (rho = 0.33,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.028). Although the Endogenous and Skin and Blood clocks were more strongly correlated with chronological age, their age acceleration estimates were not significantly associated with sun-exposure parameters or mRNA levels in skin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Skin epigenetic clocks can differentiate exogenous from endogenous skin ageing facilitating further study of the mechanisms underlying these two skin ageing phenomena.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13148-026-02230-w","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:25:08Z","timestamp":1789122308000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic clocks can differentiate between exogenous and endogenous skin ageing"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9781-1015","authenticated-orcid":false,"given":"Christopher J.","family":"Shore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy B.","family":"Simons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Ramos","family":"del Ca\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba Milena","family":"Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M. 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For the fibroblast cell collections, informed written consent and ethical review were obtained. Due to the historical nature of the studies, further ethical review for the use of these anonymised fibroblasts for their study detailed here was sought and ethical approval was granted from an NHS REC (West Midlands - Black Country NHS REC), Ageing in skin fibroblast cells; reference: 16\/WM\/0041, IRAS project ID\/approval form: 187622\/901579\/1\/330. The young and old, lower outer and upper inner arm whole-biopsy skin study (Furtak young old dataset) was an IRB approved single centre, cross-sectional biopsy study carried out in the USA, and all participants gave informed written consent. The upper buttock sun-protected epidermal study (Shyne dataset) was conducted under ethical approval granted by the University of Manchester Research Ethics Committee (reference:16112) and all participants gave informed written consent. The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus Medi\u00adcal Center (Erasmus MC) under registration number MEC 02.1015, and by the Dutch Ministry of Health, Welfare and Sport under the Population Screening Act (WBO), license number 1071272-159521-PG, in accordance with the Declaration of Helsinki. All participants provided written in\u00adform\u00aded consent to participate in the study and to have their data used for scientific research.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Exogeneous and Endogenous Skin clocks described in this manuscript are subject to a patent held by Unilever. David Gunn, Jeremy Shen and Laura Ramos del Ca\u00f1o are Unilever employees. Christopher Shore was a recipient of a BBSRC-Unilever iCASE PhD studentship. All other authors declare no conflicts of interest.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"168"}}