{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:03:00Z","timestamp":1780380180770,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intestinal senescence is an important factor in systemic aging and age\u2010related diseases; however, detailed studies have been limited due to the lack of robust experimental models. In this study, we established cellular senescence models of human small intestinal organoids using two senescence\u2010inducing agents: butyrate (an endogenous microbial metabolite) and cisplatin (an exogenous chemotherapeutic agent). Both molecules induced senescence\u2010associated features, including increased\n                    <jats:italic>p16INK4a<\/jats:italic>\n                    ,\n                    <jats:italic>CDKN1A<\/jats:italic>\n                    ,\n                    <jats:italic>IL8<\/jats:italic>\n                    , and\n                    <jats:italic>TNF<\/jats:italic>\n                    expression, as well as SA\u2010\u03b2\u2010Gal activity. RNA\u2010sequencing revealed that cisplatin, but not butyrate, activated the p53 signaling pathway, whereas both downregulated various nutrient absorption and metabolism\u2010related pathways. These models exhibited reduced nutrient transporter expression, diminished glucose uptake, and decreased vitamin D responsiveness, thus recapitulating the features of aged or damaged intestinal tissue. In cisplatin\u2010treated organoids, epithelial to mesenchymal transition (EMT)\u2010related gene ontologies were enriched based on RNA\u2010sequencing. The induction of EMT through cisplatin\u2010induced senescence was further confirmed by EMT marker gene expression, which decreased following the inhibition of TGF\u2010\u03b2 signaling, a canonical EMT\u2010inducing pathway. Notably, TGF\u2010\u03b2 signaling inhibition attenuated senescence\u2010induced inflammation and nutrient dysfunction, which suggests the importance of EMT as a target for preventing intestinal senescence. Our models provide a novel platform for examining the intestine\u2010specific molecular mechanisms of senescence associated with distinct senescence\u2010inducing mechanisms and for developing strategies to prevent age\u2010related intestinal dysfunction.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70181","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:49:14Z","timestamp":1779799754000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling and Characterization of Intestinal Senescence Using Human Organoids: Insights Into the Epithelial to Mesenchymal Transition"],"prefix":"10.1002","volume":"241","author":[{"given":"Tatsuhiro","family":"Ayabe","sequence":"first","affiliation":[{"name":"Institute of Health Sciences, Kirin Holdings Company, Limited Fujisawa Japan"},{"name":"KIRIN Central Research Institute, Kirin Holdings Company, Limited Fujisawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3186-2925","authenticated-orcid":false,"given":"Yu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u2010Ting","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kokubo","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Kirin Holdings Company, Limited Fujisawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of 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