{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T12:04:39Z","timestamp":1779710679076,"version":"3.53.1"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018694","name":"European Commission Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.ejps.2026.107513","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:48:14Z","timestamp":1773942494000},"page":"107513","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Impact of chronological ageing on tight junction-related gene expression at the human gastrointestinal epithelium: An exploratory study"],"prefix":"10.1016","volume":"221","author":[{"given":"Jonas","family":"Kusch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Argyropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Goumas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Tribonias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Reppas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-2459","authenticated-orcid":false,"given":"Maria","family":"Vertzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.ejps.2026.107513_bib0001","doi-asserted-by":"crossref","first-page":"G1054","DOI":"10.1152\/ajpgi.00055.2011","article-title":"Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier","volume":"300","author":"Al-Sadi","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.ejps.2026.107513_bib0002","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1242\/jcs.00165","article-title":"Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells","volume":"115","author":"Amasheh","year":"2002","journal-title":"J. Cell Sci."},{"issue":"19","key":"10.1016\/j.ejps.2026.107513_bib0003","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1091\/mbc.e12-09-0688","article-title":"Occludin OCEL-domain interactions are required for maintenance and regulation of the tight junction barrier to macromolecular flux","volume":"24","author":"Buschmann","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ejps.2026.107513_bib0004","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2016.10.014","article-title":"Pathophysiology, evaluation, and management of chronic watery diarrhea","volume":"152","author":"Camilleri","year":"2017","journal-title":"Gastroenterology"},{"issue":"9","key":"10.1016\/j.ejps.2026.107513_bib0005","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.261776","article-title":"A short guide to the tight junction","volume":"137","author":"Citi","year":"2024","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ejps.2026.107513_bib0006","doi-asserted-by":"crossref","first-page":"C142","DOI":"10.1152\/ajpcell.00038.2002","article-title":"Claudins create charge-selective channels in the paracellular pathway between epithelial cells","volume":"283","author":"Colegio","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.ejps.2026.107513_bib0007","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13099-021-00446-0","article-title":"Gut microbiota influence in type 2 diabetes mellitus (T2DM)","volume":"13","author":"Cunningham","year":"2021","journal-title":"Gut Pathog."},{"key":"10.1016\/j.ejps.2026.107513_bib0008","unstructured":"European Medicines Agency (EMA), 2016. ICH guideline for good clinical practice E6(R2). EMA\/CHMP\/ICH\/135\/1995. Available at: https:\/\/www.ema.europa.eu\/en\/ich-e6-good-clinical-practice-scientific-guideline (accessed 20 November 2025)."},{"key":"10.1016\/j.ejps.2026.107513_bib0009","unstructured":"Eurostat, 2024. Population structure and ageing. Available at: https:\/\/ec.europa.eu\/eurostat\/statistics-explained\/index.php?title=Population_structure_and_ageing (accessed 9 May 2025)."},{"key":"10.1016\/j.ejps.2026.107513_bib0010","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1023\/A:1016065715308","article-title":"Comparison between permeability coefficients in rat and Human jejunum","volume":"13","author":"Fagerholm","year":"1996","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2026.107513_bib0011","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1053\/j.gastro.2017.01.031","article-title":"The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association","volume":"152","author":"Freedberg","year":"2017","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejps.2026.107513_bib0012","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1091\/mbc.e07-09-0973","article-title":"Tight junction proteins claudin-2 and -12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes","volume":"19","author":"Fujita","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ejps.2026.107513_bib0013","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s11606-012-2208-0","article-title":"Gastrointestinal events with clopidogrel: a nationwide population-based cohort study","volume":"28","author":"Grove","year":"2013","journal-title":"J. Gen. Intern. Med."},{"key":"10.1016\/j.ejps.2026.107513_bib0014","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1152\/physrev.00019.2012","article-title":"Claudins and the modulation of tight junction permeability","volume":"93","author":"G\u00fcnzel","year":"2013","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejps.2026.107513_bib0015","article-title":"Overview of methotrexate toxicity: a comprehensive literature review","volume":"14","author":"Hamed","year":"2022","journal-title":"Cureus"},{"key":"10.1016\/j.ejps.2026.107513_bib0016","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.767456","article-title":"IL-1\u03b2 and the intestinal epithelial tight junction barrier","volume":"12","author":"Kaminsky","year":"2021","journal-title":"Front. Immunol."},{"issue":"2","key":"10.1016\/j.ejps.2026.107513_bib0017","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bpg.2016.02.007","article-title":"Physiology of intestinal absorption and secretion","volume":"30","author":"Kiela","year":"2016","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"10.1016\/j.ejps.2026.107513_bib0018","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2147\/CEG.S455101","article-title":"Intestinal permeability, irritable bowel syndrome with constipation, and the role of sodium-hydrogen exchanger isoform 3 (NHE3)","volume":"17","author":"Lacy","year":"2024","journal-title":"Clin. Exp. Gastroenterol."},{"issue":"6","key":"10.1016\/j.ejps.2026.107513_bib0019","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/j.1365-2362.1982.tb02230.x","article-title":"Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man","volume":"12","author":"Laker","year":"1982","journal-title":"Eur. J. Clin. Invest."},{"key":"10.1016\/j.ejps.2026.107513_bib0020","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1084\/jem.20071416","article-title":"JAM-A regulates permeability and inflammation in the intestine in vivo","volume":"204","author":"Laukoetter","year":"2007","journal-title":"J. Exp. Med."},{"issue":"6","key":"10.1016\/j.ejps.2026.107513_bib0021","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/j.1365-2125.1994.tb04309.x","article-title":"Intestinal drug absorption during induced net water absorption in man; a mechanistic study using antipyrine, atenolol and enalaprilat","volume":"37","author":"Lennern\u00e4s","year":"1994","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejps.2026.107513_bib0022","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"issue":"4","key":"10.1016\/j.ejps.2026.107513_bib0023","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212\u0394\u0394C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.ejps.2026.107513_bib0024","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/CS20150046","article-title":"Age-associated modifications of intestinal permeability and innate immunity in human small intestine","volume":"129","author":"Man","year":"2015","journal-title":"Clin. Sci."},{"key":"10.1016\/j.ejps.2026.107513_bib0025","doi-asserted-by":"crossref","first-page":"11665","DOI":"10.1074\/jbc.M412650200","article-title":"Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on \u03b21 integrins and Rap1 activity","volume":"280","author":"Mandell","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejps.2026.107513_bib0026","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/628157","article-title":"Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut","volume":"2015","author":"Michielan","year":"2015","journal-title":"Mediat. Inflamm."},{"issue":"6","key":"10.1016\/j.ejps.2026.107513_bib0027","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S2468-1253(24)00390-X","article-title":"The intestinal barrier: a pivotal role in health, inflammation, and cancer","volume":"10","author":"Neurath","year":"2025","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.ejps.2026.107513_bib0028","doi-asserted-by":"crossref","DOI":"10.1016\/j.cct.2022.106683","article-title":"Age-based exclusions in clinical trials: a review and new perspectives","volume":"114","author":"Nguyen","year":"2022","journal-title":"Contemp. Clin. Trials"},{"issue":"7","key":"10.1016\/j.ejps.2026.107513_bib0029","doi-asserted-by":"crossref","DOI":"10.14309\/ctg.0000000000000428","article-title":"Altered mucosal immune-microbiota interactions in familial adenomatous polyposis","volume":"13","author":"Noble","year":"2022","journal-title":"Clin. Transl. Gastroenterol."},{"key":"10.1016\/j.ejps.2026.107513_bib0030","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF02209146","article-title":"Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and hamsters","volume":"100","author":"Pappenheimer","year":"1987","journal-title":"J. Membr. Biol."},{"key":"10.1016\/j.ejps.2026.107513_bib0031","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1532-5415.1995.tb06382.x","article-title":"Changes in small-intestine permeability with ageing","volume":"43","author":"Saltzman","year":"1995","journal-title":"J. Am. Geriatr. Soc."},{"issue":"5","key":"10.1016\/j.ejps.2026.107513_bib0032","doi-asserted-by":"crossref","first-page":"G397","DOI":"10.1152\/ajpgi.1981.241.5.G397","article-title":"Conservation of mannitol, lactulose, and raffinose by the human colon","volume":"241","author":"Saunders","year":"1981","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.ejps.2026.107513_bib0033","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/ageing\/14.5.312","article-title":"The double sugar test of intestinal permeability in the elderly","volume":"14","author":"Saweirs","year":"1985","journal-title":"Age Ageing"},{"issue":"4","key":"10.1016\/j.ejps.2026.107513_bib0034","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2174\/1573401313666170427162740","article-title":"Intestinal absorption and factors influencing bioavailability of magnesium\u2014an update","volume":"13","author":"Schuchardt","year":"2017","journal-title":"Curr. Nutr. Food Sci."},{"key":"10.1016\/j.ejps.2026.107513_bib0035","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-physiol-012110-142150","article-title":"Tight junction pore and leak pathways: a dynamic duo","volume":"73","author":"Shen","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.ejps.2026.107513_bib0036","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1126\/science.aar3318","article-title":"Hyperglycemia drives intestinal barrier dysfunction and increases the risk of enteric infection","volume":"359","author":"Thaiss","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ejps.2026.107513_bib0037","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejps.2026.107513_bib0038","unstructured":"U.S. Food and Drug Administration (FDA), 2025. Novel drug approvals at FDA. Available at: https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/novel-drug-approvals-fda (accessed 20 November 2025)."},{"issue":"4","key":"10.1016\/j.ejps.2026.107513_bib0039","doi-asserted-by":"crossref","DOI":"10.1002\/phy2.281","article-title":"Small intestinal permeability in older adults","volume":"2","author":"Valentini","year":"2014","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.ejps.2026.107513_bib0040","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1242\/jcs.021485","article-title":"The density of small tight junction pores varies among cell types and is increased by the expression of claudin-2","volume":"121","author":"Van Itallie","year":"2008","journal-title":"J. Cell Sci."},{"issue":"17","key":"10.1016\/j.ejps.2026.107513_bib0041","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1091\/mbc.e09-04-0320","article-title":"ZO-1 stabilizes the tight junction solute barrier through coupling to the perijunctional cytoskeleton","volume":"20","author":"Van Itallie","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.ejps.2026.107513_bib0042","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2021.717925","article-title":"The role of intestinal permeability in gastrointestinal disorders and current methods of evaluation","volume":"8","author":"Vanuytsel","year":"2021","journal-title":"Front. Nutr."},{"key":"10.1016\/j.ejps.2026.107513_bib0043","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ejps.2026.107513_bib0044","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1152\/ajpcell.2001.281.2.C388","article-title":"Functional modeling of tight junctions in intestinal cell monolayers using polyethylene glycol oligomers","volume":"281","author":"Watson","year":"2001","journal-title":"Am. J. Physiol. Physiol."},{"key":"10.1016\/j.ejps.2026.107513_bib0045","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.09906","article-title":"Claudin-2-dependent paracellular channels are dynamically gated","volume":"4","author":"Weber","year":"2015","journal-title":"ELife"},{"key":"10.1016\/j.ejps.2026.107513_bib0046","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41598-019-57106-2","article-title":"Intestinal barrier function is maintained with ageing: a comprehensive study in healthy subjects and irritable bowel syndrome patients","volume":"10","author":"Wilms","year":"2020","journal-title":"Sci. Rep."},{"issue":"20","key":"10.1016\/j.ejps.2026.107513_bib0047","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"10.1016\/j.ejps.2026.107513_bib0048","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/gut.2006.094375","article-title":"Changes in expression and distribution of claudins 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease","volume":"56","author":"Zeissig","year":"2007","journal-title":"Gut"},{"key":"10.1016\/j.ejps.2026.107513_bib0049","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1023\/A:1018974519984","article-title":"Regulation of paracellular absorption of cimetidine and 5-aminosalicylate in rat intestine","volume":"16","author":"Zhou","year":"1999","journal-title":"Pharm. Res."}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098726000874?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098726000874?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:49:18Z","timestamp":1779709758000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098726000874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":49,"alternative-id":["S0928098726000874"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2026.107513","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Impact of chronological ageing on tight junction-related gene expression at the human gastrointestinal epithelium: An exploratory study","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2026.107513","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"107513"}}