{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:55:34Z","timestamp":1777521334233,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Preclinical human skin ageing research has been limited by the paucity of instructive and clinically relevant models. In this pilot study, we report that healthy human skin of different age groups undergoes extremely accelerated ageing within only 3\u2009days, if organ\u2010cultured in a defined serum\u2010free medium. Quantitative (immuno\u2010)histomorphometry documented this unexpected ex\u00a0vivo phenotype on the basis of ageing\u2010associated biomarkers: the epidermis showed significantly reduced rete ridges and keratinocyte proliferation, sirtuin\u20101, MTCO1 and collagen 17a1 protein levels; this contrasted with significantly increased expression of the DNA\u2010damage marker, \u03b3H2A.X. In the dermis, collagen 1 and 3 and hyaluronic acid content were significantly reduced compared to Day 0 skin. qRT\u2010PCR of whole skin RNA extracts also showed up\u2010regulated mRNA levels of several (inflamm\u2010) ageing biomarkers (\n                    <jats:italic>MMP\u20101<\/jats:italic>\n                    ,\n                    <jats:italic>\u20102<\/jats:italic>\n                    ,\n                    <jats:italic>\u20103<\/jats:italic>\n                    ,\n                    <jats:italic>\u20109<\/jats:italic>\n                    ;\n                    <jats:italic>IL6<\/jats:italic>\n                    ,\n                    <jats:italic>IL8<\/jats:italic>\n                    ,\n                    <jats:italic>CXCL10<\/jats:italic>\n                    and\n                    <jats:italic>CDKN1<\/jats:italic>\n                    ). Caffeine, a methylxanthine with recognized anti\u2010ageing properties, counteracted the dermal collagen 1 and 3 reduction, the epidermal accumulation of \u03b3H2A.X, and the up\u2010regulation of\n                    <jats:italic>CXCL10<\/jats:italic>\n                    ,\n                    <jats:italic>IL6<\/jats:italic>\n                    ,\n                    <jats:italic>IL8<\/jats:italic>\n                    ,\n                    <jats:italic>MMP2<\/jats:italic>\n                    and\n                    <jats:italic>CDKN1<\/jats:italic>\n                    . Finally, we present novel anti\u2010ageing effects of topical 2,5\u2010dimethylpyrazine, a natural pheromone TRPM5 ion channel activator. Thus, this instructive, clinically relevant \u201cspeed\u2010ageing\u201d assay provides a simple, but powerful new research tool for dissecting skin ageing and rejuvenation, and is well\u2010suited to identify novel anti\u2010ageing actives directly in the human target organ.\n                  <\/jats:p>","DOI":"10.1111\/exd.14955","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T00:11:21Z","timestamp":1698451881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u2018Speed\u2010ageing\u2019 of human skin in serum\u2010free organ culture ex\u00a0vivo: An instructive novel assay for preclinical human skin ageing research demonstrates senolytic effects of caffeine and 2,5\u2010dimethylpyrazine"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6892-0792","authenticated-orcid":false,"given":"Max","family":"van Lessen","sequence":"first","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-5506","authenticated-orcid":false,"given":"Andrei","family":"Mardaryev","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"},{"name":"Centre for Skin Sciences, School of Chemistry and Bioscience University of Bradford  Bradford United\u00a0Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2405-1040","authenticated-orcid":false,"given":"David","family":"Broadley","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-6998","authenticated-orcid":false,"given":"Marta","family":"Bertolini","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-3890","authenticated-orcid":false,"given":"Janin","family":"Edelkamp","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"K\u00fcckelhaus","sequence":"additional","affiliation":[{"name":"Fachklinik Hornheide  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Funk","sequence":"additional","affiliation":[{"name":"Klinik Dr. Funk  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-6221","authenticated-orcid":false,"given":"Tam\u00e1s","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory  M\u00fcnster Germany"},{"name":"Cutaneon  Hamburg 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