{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:02:45Z","timestamp":1787065365317,"version":"build-2736575974"},"reference-count":79,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"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":["Aging Cell"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging is associated with a decline in the regenerative capacity of many tissues. Central to this decline is a complex interplay between inflammation and stem cell function. How these two processes are linked and influence regenerative capacity remains unclear. Here, we undertake a comprehensive assessment of age\u2010related changes in the mouse colon at single\u2010cell resolution. A survey of immune and epithelial compartments revealed a hyperactivated inflammatory state in the colon of old mice characterized, among other changes, by the induction of an interferon \u03b3 (IFN\u03b3) response signature in immune cells. This does not result in increased inflammatory signatures in the epithelium under homeostasis but triggers a disproportionate inflammatory response that disrupts regeneration and epithelial integrity after challenge with the enteropathogen\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Citrobacter rodentium<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Colons of old mice exhibit higher production of IFN\u03b3 by T and innate lymphoid cells (ILCs) that are associated with reduced Lgr5\n                    <jats:sup>+<\/jats:sup>\n                    stem cells and decreased epithelial proliferation. Interestingly, we find that aged intestinal epithelial cells express an elevated regeneration\u2010associated fetal\u2010like gene expression signature that, in turn, renders these cells more sensitive to IFN\u03b3\u2010induced apoptosis. Our findings reveal an age\u2010related imbalance in the interaction between the immune and epithelial compartments in the colon, priming the system for excessive inflammatory responses and the emergence of a hypersensitive epithelial cell state thus derailing proper repair of the intestinal epithelium after injury.\n                  <\/jats:p>","DOI":"10.1111\/acel.70495","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:26:06Z","timestamp":1776684366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Maladaptive Inflammatory Signaling in Old Mice Impairs Colonic Regeneration by Promoting a Sustained Fetal\u2010Like Epithelial State"],"prefix":"10.1111","volume":"25","author":[{"given":"Antonion","family":"Korcari","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine Genentech, Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Tauc","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine Genentech, Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Duggan","sequence":"additional","affiliation":[{"name":"Department of Immunology Genentech, Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jina","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine Genentech, Inc  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Wehbe","sequence":"additional","affiliation":[{"name":"Computational Sciences Center of Excellence Genentech, Inc  South San Francisco California 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L. C.Garrett Wilson A. S.Chadha et\u00a0al.2023.\u201cA Novel Subset of Colonocytes Targeted by Citrobacter Rodentium Elicits Epithelial MHCII\u2011Restricted Help From CD4 T Cells.\u201dbioRxiv.https:\/\/doi.org\/10.1101\/2023.05.03.539269.","DOI":"10.1101\/2023.05.03.539269"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2018.06.008"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T22:18:20Z","timestamp":1779401900000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":79,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/acel.70495"],"URL":"https:\/\/doi.org\/10.1111\/acel.70495","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.07.16.665215","asserted-by":"object"}]},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"assertion":[{"value":"2025-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70495"}}