{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:36:05Z","timestamp":1791441365605,"version":"4.3.3"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":53,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-48648-3","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:54:42Z","timestamp":1776336882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fibroblast-derived matrix human skin equivalents reveal distinct roles for papillary and reticular fibroblasts in human skin barrier integrity and aging"],"prefix":"10.1038","volume":"16","author":[{"given":"Alesha","family":"Louis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Mergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion H.","family":"Rietveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Gendronneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Andre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcef","family":"Ben Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke A.","family":"Bouwstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rissmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rym","family":"Halkoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoelwaheb","family":"El Ghalbzouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"48648_CR1","first-page":"297","volume":"10","author":"JA Bouwstra","year":"2007","unstructured":"Bouwstra, J. A., Gooris, G. & Ponec, M. Skin lipid organization, composition and barrier function. Int. J. Cosmet. Sci. 10, 297\u2013307 (2007).","journal-title":"Int. J. Cosmet. Sci."},{"key":"48648_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1159\/000441540","volume":"49","author":"J van Smeden","year":"2016","unstructured":"van Smeden, J. & Bouwstra, J. A. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients. Curr. Probl. Dermatol. 49, 8\u201326. https:\/\/doi.org\/10.1159\/000441540 (2016).","journal-title":"Curr. Probl. Dermatol."},{"key":"48648_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2022.101184","author":"P Sharamprasad","year":"2022","unstructured":"Sharamprasad, P. et al. Using molecular simulation to understand the skin barrier. Elsevier https:\/\/doi.org\/10.1016\/j.plipres.2022.101184 (2022).","journal-title":"Elsevier"},{"key":"48648_CR4","doi-asserted-by":"publisher","unstructured":"Gorcea, M., Lane, M. E. & Moore, D. J. Exploratory in vivo biophysical studies of stratum corneum lipid organization in human face and arm skin. Int. J. Pharm. 622 https:\/\/doi.org\/10.1016\/j.ijpharm.2022.121887 (2022).","DOI":"10.1016\/j.ijpharm.2022.121887"},{"key":"48648_CR5","doi-asserted-by":"publisher","unstructured":"Kim, J. C., Park, T. J. & Kang, H. Y. Skin-Aging Pigmentation: Who Is the Real Enemy? Cells 11 https:\/\/doi.org\/10.3390\/cells11162541 (2022).","DOI":"10.3390\/cells11162541"},{"key":"48648_CR6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/978-3-540-89656-2_5","volume":"5","author":"C Raschke","year":"2010","unstructured":"Raschke, C. & Elsner, P. Textbook Aging Skin Ch Chapter 5, 37\u201343 (2010).","journal-title":"Textbook Aging Skin Ch Chapter"},{"key":"48648_CR7","doi-asserted-by":"publisher","first-page":"e4066","DOI":"10.1371\/journal.pone.0004066","volume":"3","author":"S Mine","year":"2008","unstructured":"Mine, S., Fortunel, N. O., Pageon, H. & Asselineau, D. Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: a new view of skin morphogenesis and aging. PLoS One. 3, e4066. https:\/\/doi.org\/10.1371\/journal.pone.0004066 (2008).","journal-title":"PLoS One"},{"key":"48648_CR8","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1038\/jid.2012.192","volume":"132","author":"DG Janson","year":"2012","unstructured":"Janson, D. G., Saintigny, G., van Adrichem, A. & Mahe, C. El Ghalbzouri, A. Different gene expression patterns in human papillary and reticular fibroblasts. J. Invest. Dermatol. 132, 2565\u20132572. https:\/\/doi.org\/10.1038\/jid.2012.192 (2012).","journal-title":"J. Invest. Dermatol."},{"key":"48648_CR9","doi-asserted-by":"publisher","unstructured":"Wu, S. et al. Human Papillary and Reticular Fibroblasts Show Distinct Functions on Tumor Behavior in 3D-Organotypic Cultures Mimicking Melanoma and HNSCC. Int. J. Mol. Sci. 23 https:\/\/doi.org\/10.3390\/ijms231911651 (2022).","DOI":"10.3390\/ijms231911651"},{"key":"48648_CR10","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/exd.12069","volume":"22","author":"D Janson","year":"2013","unstructured":"Janson, D., Saintigny, G. & Mahe, C. El Ghalbzouri, A. Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture. Exp. Dermatol. 22, 48\u201353. https:\/\/doi.org\/10.1111\/exd.12069 (2013).","journal-title":"Exp. Dermatol."},{"key":"48648_CR11","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/exd.13531","volume":"27","author":"H Niehues","year":"2018","unstructured":"Niehues, H. et al. 3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function. Exp. Dermatol. 27, 501\u2013511. https:\/\/doi.org\/10.1111\/exd.13531 (2018).","journal-title":"Exp. Dermatol."},{"key":"48648_CR12","doi-asserted-by":"publisher","unstructured":"Huth, S. et al. An Improved Human 3-Dimensional Skin Model for Aging Research. J Invest Dermatol 146, 535\u2013539 e534 (2026). https:\/\/doi.org\/10.1016\/j.jid.2025.07.005","DOI":"10.1016\/j.jid.2025.07.005"},{"key":"48648_CR13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.biomaterials.2008.09.002","volume":"30","author":"A El Ghalbzouri","year":"2009","unstructured":"El Ghalbzouri, A., Commandeur, S., Rietveld, M. H., Mulder, A. A. & Willemze, R. Replacement of animal-derived collagen matrix by human fibroblast-derived dermal matrix for human skin equivalent products. Biomaterials 30, 71\u201378. https:\/\/doi.org\/10.1016\/j.biomaterials.2008.09.002 (2009).","journal-title":"Biomaterials"},{"key":"48648_CR14","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1684\/ejd.2017.2984","volume":"27","author":"D Janson","year":"2017","unstructured":"Janson, D., Rietveld, M., Mahe, C., Saintigny, G. & El Ghalbzouri, A. Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development in vitro. Eur. J. Dermatol. 27, 237\u2013246. https:\/\/doi.org\/10.1684\/ejd.2017.2984 (2017).","journal-title":"Eur. J. Dermatol."},{"key":"48648_CR15","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/jid.2012.262","volume":"133","author":"VS Thakoersing","year":"2013","unstructured":"Thakoersing, V. S. et al. Increased presence of monounsaturated fatty acids in the stratum corneum of human skin equivalents. J. Invest. Dermatol. 133, 59\u201367. https:\/\/doi.org\/10.1038\/jid.2012.262 (2013).","journal-title":"J. Invest. Dermatol."},{"key":"48648_CR16","doi-asserted-by":"publisher","first-page":"e0174478","DOI":"10.1371\/journal.pone.0174478","volume":"12","author":"A Mieremet","year":"2017","unstructured":"Mieremet, A. et al. Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices. PLoS One. 12, e0174478. https:\/\/doi.org\/10.1371\/journal.pone.0174478 (2017).","journal-title":"PLoS One"},{"key":"48648_CR17","doi-asserted-by":"publisher","first-page":"101252","DOI":"10.1016\/j.plipres.2023.101252","volume":"92","author":"JA Bouwstra","year":"2023","unstructured":"Bouwstra, J. A. et al. The skin barrier: An extraordinary interface with an exceptional lipid organization. Prog Lipid Res. 92, 101252. https:\/\/doi.org\/10.1016\/j.plipres.2023.101252 (2023).","journal-title":"Prog Lipid Res."},{"key":"48648_CR18","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/exd.12293","volume":"23","author":"J van Smeden","year":"2014","unstructured":"van Smeden, J. et al. The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp. Dermatol. 23, 45\u201352. https:\/\/doi.org\/10.1111\/exd.12293 (2014).","journal-title":"Exp. Dermatol."},{"key":"48648_CR19","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/j.ajpath.2020.03.007","volume":"190","author":"E Russell-Goldman","year":"2020","unstructured":"Russell-Goldman, E. & Murphy, G. F. The Pathobiology of Skin Aging: New Insights into an Old Dilemma. Am. J. Pathol. 190, 1356\u20131369. https:\/\/doi.org\/10.1016\/j.ajpath.2020.03.007 (2020).","journal-title":"Am. J. Pathol."},{"key":"48648_CR20","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1111\/ics.12779","volume":"44","author":"D Zargaran","year":"2022","unstructured":"Zargaran, D., Zoller, F., Zargaran, A., Weyrich, T. & Mosahebi, A. Facial skin ageing: Key concepts and overview of processes. Int. J. Cosmet. Sci. 44, 414\u2013420. https:\/\/doi.org\/10.1111\/ics.12779 (2022).","journal-title":"Int. J. Cosmet. Sci."},{"key":"48648_CR21","doi-asserted-by":"publisher","unstructured":"Karimi, N. & Ahmadi, V. Aquaporin Channels in Skin Physiology and Aging Pathophysiology: Investigating Their Role in Skin Function and the Hallmarks of Aging. Biology (Basel). 13. https:\/\/doi.org\/10.3390\/biology13110862 (2024).","DOI":"10.3390\/biology13110862"},{"key":"48648_CR22","doi-asserted-by":"publisher","unstructured":"Briganti, S., Mosca, S., Di Nardo, A., Flori, E. & Ottaviani, M. New Insights into the Role of PPARgamma in Skin Physiopathology. Biomolecules 14 https:\/\/doi.org\/10.3390\/biom14060728 (2024).","DOI":"10.3390\/biom14060728"},{"key":"48648_CR23","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1172\/JCI97949","volume":"128","author":"M Trayssac","year":"2018","unstructured":"Trayssac, M., Hannun, Y. A. & Obeid, L. M. Role of sphingolipids in senescence: implication in aging and age-related diseases. J. Clin. Invest. 128, 2702\u20132712. https:\/\/doi.org\/10.1172\/JCI97949 (2018).","journal-title":"J. Clin. Invest."},{"key":"48648_CR24","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1021\/acs.langmuir.1c01295","volume":"37","author":"LE Uche","year":"2021","unstructured":"Uche, L. E., Gooris, G. S., Bouwstra, J. A. & Beddoes, C. M. Increased Levels of Short-Chain Ceramides Modify the Lipid Organization and Reduce the Lipid Barrier of Skin Model Membranes. Langmuir 37, 9478\u20139489. https:\/\/doi.org\/10.1021\/acs.langmuir.1c01295 (2021).","journal-title":"Langmuir"},{"key":"48648_CR25","doi-asserted-by":"publisher","unstructured":"Trayssac, M. et al. Targeting sphingosine kinase 1 (SK1) enhances oncogene-induced senescence through ceramide synthase 2 (CerS2)-mediated generation of verylong-chain ceramides. Cell Death Dis. 12 https:\/\/doi.org\/10.1038\/s41419-020-03281-4 (2021).","DOI":"10.1038\/s41419-020-03281-4"},{"key":"48648_CR26","doi-asserted-by":"publisher","first-page":"1297637","DOI":"10.3389\/fphys.2023.1297637","volume":"14","author":"T Chin","year":"2023","unstructured":"Chin, T., Lee, X. E., Ng, P. Y., Lee, Y. & Dreesen, O. The role of cellular senescence in skin aging and age-related skin pathologies. Front. Physiol. 14, 1297637. https:\/\/doi.org\/10.3389\/fphys.2023.1297637 (2023).","journal-title":"Front. Physiol."},{"key":"48648_CR27","doi-asserted-by":"publisher","unstructured":"Hong, J. Y. et al. Sprr1 and miR-130b contribute to the senescence-like phenotype in aging. bioRxiv (2023). https:\/\/doi.org\/10.1101\/2023.10.25.563779","DOI":"10.1101\/2023.10.25.563779"},{"key":"48648_CR28","doi-asserted-by":"publisher","unstructured":"Lee, G. et al. SREBP1c-PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity. Cell Metab 34, 702\u2013718 e705 (2022). https:\/\/doi.org\/10.1016\/j.cmet.2022.03.010","DOI":"10.1016\/j.cmet.2022.03.010"},{"key":"48648_CR29","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.bpc.2017.03.004","volume":"224","author":"P Pullmannova","year":"2017","unstructured":"Pullmannova, P. et al. Permeability and microstructure of model stratum corneum lipid membranes containing ceramides with long (C16) and very long (C24) acyl chains. Biophys. Chem. 224, 20\u201331. https:\/\/doi.org\/10.1016\/j.bpc.2017.03.004 (2017).","journal-title":"Biophys. Chem."},{"key":"48648_CR30","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1016\/j.bpj.2015.04.030","volume":"108","author":"EH Mojumdar","year":"2015","unstructured":"Mojumdar, E. H. et al. Skin lipids: localization of ceramide and fatty acid in the unit cell of the long periodicity phase. Biophys. J. 108, 2670\u20132679. https:\/\/doi.org\/10.1016\/j.bpj.2015.04.030 (2015).","journal-title":"Biophys. J."},{"key":"48648_CR31","doi-asserted-by":"publisher","first-page":"100400","DOI":"10.1016\/j.jlr.2023.100400","volume":"64","author":"A Nadaban","year":"2023","unstructured":"Nadaban, A. et al. Effect of sphingosine and phytosphingosine ceramide ratio on lipid arrangement and barrier function in skin lipid models. J. Lipid Res. 64, 100400. https:\/\/doi.org\/10.1016\/j.jlr.2023.100400 (2023).","journal-title":"J. Lipid Res."},{"key":"48648_CR32","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jdermsci.2017.05.005","volume":"88","author":"M Danso","year":"2017","unstructured":"Danso, M. et al. Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J. Dermatol. Sci. 88, 57\u201366. https:\/\/doi.org\/10.1016\/j.jdermsci.2017.05.005 (2017).","journal-title":"J. Dermatol. Sci."},{"key":"48648_CR33","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1111\/all.16660","volume":"80","author":"M Braskett","year":"2025","unstructured":"Braskett, M. et al. Lipidomic Analysis of Esophageal Epithelia Reveals a Distinctive Sphingolipid Profile in Eosinophilic Esophagitis. Allergy 80, 2849\u20132860. https:\/\/doi.org\/10.1111\/all.16660 (2025).","journal-title":"Allergy"},{"key":"48648_CR34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.plipres.2016.04.001","volume":"63","author":"A Kihara","year":"2016","unstructured":"Kihara, A. Synthesis and degradation pathways, functions, and pathology of ceramides and epidermal acylceramides. Prog Lipid Res. 63, 50\u201369. https:\/\/doi.org\/10.1016\/j.plipres.2016.04.001 (2016).","journal-title":"Prog Lipid Res."},{"key":"48648_CR35","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1046\/j.1523-1747.2000.00941.x","volume":"114","author":"V Schreiner","year":"2000","unstructured":"Schreiner, V. et al. Barrier characteristics of different human skin types investigated with X-ray diffraction, lipid analysis, and electron microscopy imaging. J. Invest. Dermatol. 114, 654\u2013660. https:\/\/doi.org\/10.1046\/j.1523-1747.2000.00941.x (2000).","journal-title":"J. Invest. Dermatol."},{"key":"48648_CR36","doi-asserted-by":"publisher","first-page":"100383","DOI":"10.1016\/j.xjidi.2025.100383","volume":"5","author":"DO Dina","year":"2025","unstructured":"Dina, D. O., Maiellaro, M., Camera, E. & Connelly, J. T. Development of Human Skin Equivalents with Inducible Ceramide Depletion for In Vitro Modeling of Lipid Impairment. JID Innov. 5, 100383. https:\/\/doi.org\/10.1016\/j.xjidi.2025.100383 (2025).","journal-title":"JID Innov."},{"key":"48648_CR37","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/ics.12972","volume":"46","author":"J Schild","year":"2024","unstructured":"Schild, J., Kalvodov\u00e1, A., Zbytovska, J., Farwick, M. & Pyko, C. The role of ceramides in skin barrier function and the importance of their correct formulation for skincare applications. Int. J. Cosmet. Sci. 46, 526\u2013543. https:\/\/doi.org\/10.1111\/ics.12972 (2024).","journal-title":"Int. J. Cosmet. Sci."},{"key":"48648_CR38","doi-asserted-by":"publisher","first-page":"21715","DOI":"10.1038\/s41598-022-26095-0","volume":"12","author":"AC Kendall","year":"2022","unstructured":"Kendall, A. C. et al. Menopause induces changes to the stratum corneum ceramide profile, which are prevented by hormone replacement therapy. Sci. Rep. 12, 21715. https:\/\/doi.org\/10.1038\/s41598-022-26095-0 (2022).","journal-title":"Sci. Rep."},{"key":"48648_CR39","doi-asserted-by":"publisher","first-page":"183487","DOI":"10.1016\/j.bbamem.2020.183487","volume":"1863","author":"LE Uche","year":"2021","unstructured":"Uche, L. E., Gooris, G. S., Bouwstra, J. A. & Beddoes, C. M. High concentration of the ester-linked omega-hydroxy ceramide increases the permeability in skin lipid model membranes. Biochim. Biophys. Acta Biomembr. 1863, 183487. https:\/\/doi.org\/10.1016\/j.bbamem.2020.183487 (2021).","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"48648_CR40","doi-asserted-by":"publisher","first-page":"4326","DOI":"10.1039\/c4sm02786h","volume":"11","author":"EH Mojumdar","year":"2015","unstructured":"Mojumdar, E. H., Gooris, G. S. & Bouwstra, J. A. Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization. Soft Matter. 11, 4326\u20134336. https:\/\/doi.org\/10.1039\/c4sm02786h (2015).","journal-title":"Soft Matter"},{"key":"48648_CR41","doi-asserted-by":"publisher","first-page":"120","DOI":"10.7150\/ijbs.3.120","volume":"3","author":"W Li","year":"2007","unstructured":"Li, W. et al. Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 deficient mice. Int. J. Biol. Sci. 3, 120\u2013128 (2007).","journal-title":"Int. J. Biol. Sci."},{"key":"48648_CR42","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1194\/jlr.RA120000639","volume":"61","author":"J van Smeden","year":"2020","unstructured":"van Smeden, J. et al. Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities. J. Lipid Res. 61, 859\u2013869. https:\/\/doi.org\/10.1194\/jlr.RA120000639 (2020).","journal-title":"J. Lipid Res."},{"key":"48648_CR43","doi-asserted-by":"publisher","first-page":"100177","DOI":"10.1016\/j.jlr.2022.100177","volume":"63","author":"F Fandrei","year":"2022","unstructured":"Fandrei, F. et al. Cholesterol sulfate fluidizes the sterol fraction of the stratum corneum lipid phase and increases its permeability. J. Lipid Res. 63, 100177. https:\/\/doi.org\/10.1016\/j.jlr.2022.100177 (2022).","journal-title":"J. Lipid Res."},{"key":"48648_CR44","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.jff.2019.04.011","volume":"57","author":"X Wang","year":"2019","unstructured":"Wang, X. & Wu, J. Modulating effect of fatty acids and sterols on skin aging. J. Funct. Foods. 57, 135\u2013140. https:\/\/doi.org\/10.1016\/j.jff.2019.04.011 (2019).","journal-title":"J. Funct. Foods."},{"key":"48648_CR45","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/j.1346-8138.2004.tb00565.x","volume":"31","author":"H Hashizume","year":"2004","unstructured":"Hashizume, H. Skin aging and dry skin. J. Dermatol. 31, 603\u2013609. https:\/\/doi.org\/10.1111\/j.1346-8138.2004.tb00565.x (2004).","journal-title":"J. Dermatol."},{"key":"48648_CR46","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/sj.jid.5700994","volume":"128","author":"JA Bouwstra","year":"2008","unstructured":"Bouwstra, J. A., Groenink, H. W., Kempenaar, J. A., Romeijn, S. G. & Ponec, M. Water distribution and natural moisturizer factor content in human skin equivalents are regulated by environmental relative humidity. J. Invest. Dermatol. 128, 378\u2013388. https:\/\/doi.org\/10.1038\/sj.jid.5700994 (2008).","journal-title":"J. Invest. Dermatol."},{"key":"48648_CR47","doi-asserted-by":"publisher","first-page":"670","DOI":"10.14336\/AD.2022.1116","volume":"14","author":"C Statzer","year":"2023","unstructured":"Statzer, C., Park, J. Y. C. & Ewald, C. Y. Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity. Aging Dis. 14, 670\u2013693. https:\/\/doi.org\/10.14336\/AD.2022.1116 (2023).","journal-title":"Aging Dis."},{"key":"48648_CR48","doi-asserted-by":"publisher","first-page":"e2300223","DOI":"10.1002\/bies.202300223","volume":"46","author":"MJ Dalby","year":"2024","unstructured":"Dalby, M. J. et al. Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community. Bioessays 46, e2300223. https:\/\/doi.org\/10.1002\/bies.202300223 (2024).","journal-title":"Bioessays"},{"key":"48648_CR49","doi-asserted-by":"publisher","first-page":"e14054","DOI":"10.1111\/acel.14054","volume":"23","author":"J Zhang","year":"2024","unstructured":"Zhang, J., Yu, H., Man, M. Q. & Hu, L. Aging in the dermis: Fibroblast senescence and its significance. Aging Cell. 23, e14054. https:\/\/doi.org\/10.1111\/acel.14054 (2024).","journal-title":"Aging Cell."},{"key":"48648_CR50","doi-asserted-by":"publisher","first-page":"1592596","DOI":"10.3389\/fphar.2025.1592596","volume":"16","author":"L Nan","year":"2025","unstructured":"Nan, L., Guo, P., Hui, W., Xia, F. & Yi, C. Recent advances in dermal fibroblast senescence and skin aging: unraveling mechanisms and pioneering therapeutic strategies. Front. Pharmacol. 16, 1592596. https:\/\/doi.org\/10.3389\/fphar.2025.1592596 (2025).","journal-title":"Front. Pharmacol."},{"key":"48648_CR51","doi-asserted-by":"publisher","first-page":"e0219165","DOI":"10.1371\/journal.pone.0219165","volume":"14","author":"JC Lago","year":"2019","unstructured":"Lago, J. C. & Puzzi, M. B. The effect of aging in primary human dermal fibroblasts. PLoS One. 14, e0219165. https:\/\/doi.org\/10.1371\/journal.pone.0219165 (2019).","journal-title":"PLoS One"},{"key":"48648_CR52","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1038\/s41598-022-04767-1","volume":"12","author":"B Lynch","year":"2022","unstructured":"Lynch, B. et al. A mechanistic view on the aging human skin through ex vivo layer-by-layer analysis of mechanics and microstructure of facial and mammary dermis. Sci. Rep. 12, 849. https:\/\/doi.org\/10.1038\/s41598-022-04767-1 (2022).","journal-title":"Sci. Rep."},{"key":"48648_CR53","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.actbio.2023.06.040","volume":"168","author":"A Mauroux","year":"2023","unstructured":"Mauroux, A. et al. Papillary and reticular fibroblasts generate distinct microenvironments that differentially impact angiogenesis. Acta Biomater. 168, 210\u2013222. https:\/\/doi.org\/10.1016\/j.actbio.2023.06.040 (2023).","journal-title":"Acta Biomater."},{"key":"48648_CR54","doi-asserted-by":"publisher","first-page":"682414","DOI":"10.3389\/fcell.2021.682414","volume":"9","author":"K Pfisterer","year":"2021","unstructured":"Pfisterer, K., Shaw, L. E., Symmank, D. & Weninger, W. The Extracellular Matrix in Skin Inflammation and Infection. Front. Cell. Dev. Biol. 9, 682414. https:\/\/doi.org\/10.3389\/fcell.2021.682414 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"key":"48648_CR55","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s12079-018-0459-1","volume":"12","author":"MA Cole","year":"2018","unstructured":"Cole, M. A., Quan, T., Voorhees, J. J. & Fisher, G. J. Extracellular matrix regulation of fibroblast function: redefining our perspective on skin aging. J. Cell. Commun. Signal. 12, 35\u201343. https:\/\/doi.org\/10.1007\/s12079-018-0459-1 (2018).","journal-title":"J. Cell. Commun. Signal."},{"key":"48648_CR56","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nrm3904","volume":"15","author":"C Bonnans","year":"2014","unstructured":"Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell. Biol. 15, 786\u2013801. https:\/\/doi.org\/10.1038\/nrm3904 (2014).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"48648_CR57","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nrm3902","volume":"15","author":"JK Mouw","year":"2014","unstructured":"Mouw, J. K., Ou, G. & Weaver, V. M. Extracellular matrix assembly: a multiscale deconstruction. Nat. Rev. Mol. Cell. Biol. 15, 771\u2013785. https:\/\/doi.org\/10.1038\/nrm3902 (2014).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"48648_CR58","doi-asserted-by":"publisher","first-page":"3829","DOI":"10.3390\/cimb45050247","volume":"45","author":"A Zorina","year":"2023","unstructured":"Zorina, A. et al. Dermal Fibroblasts as the Main Target for Skin Anti-Age Correction Using a Combination of Regenerative Medicine Methods. Curr. Issues Mol. Biol. 45, 3829\u20133847. https:\/\/doi.org\/10.3390\/cimb45050247 (2023).","journal-title":"Curr. Issues Mol. Biol."},{"key":"48648_CR59","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1016\/j.bbalip.2016.07.004","volume":"1861","author":"W Boiten","year":"2016","unstructured":"Boiten, W., Absalah, S., Vreeken, R., Bouwstra, J. & van Smeden, J. Quantitative analysis of ceramides using a novel lipidomics approach with three dimensional response modelling. Biochim. Biophys. Acta. 1861, 1652\u20131661. https:\/\/doi.org\/10.1016\/j.bbalip.2016.07.004 (2016).","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48648-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48648-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48648-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:19:50Z","timestamp":1780877990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48648-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["48648"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-48648-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"11 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17668"}}