{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:27:50Z","timestamp":1793683670120,"version":"4.5.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The intestinal epithelium serves as a physical and functional barrier against harmful substances, preventing their entry into the circulation and subsequent induction of a systemic immune response. Gut barrier dysfunction has recently emerged as a feature of ageing linked to declining health, and increased intestinal membrane permeability has been shown to promote heightened systemic inflammation in aged hosts. Concurrent with age\u2010related changes in the gut microbiome, the thymic microenvironment undergoes a series of morphological, phenotypical and architectural alterations with age, including disorganisation of the corticomedullary junction, increased fibrosis, increased thymic adiposity and the accumulation of senescent cells. However, a direct link between gut barrier dysbiosis and thymic involution leading to features of immune ageing has not been explored thus far. Herein, we reveal strong associations between enhanced microbial translocation and the peripheral accumulation of terminally differentiated, senescent and exhausted T cells and the compensatory expansion of regulatory T cells in older adults. Crucially, we demonstrate that aged germ\u2010free mice are protected from age\u2010related increases in intestinal permeability, highlighting the direct impact of mucosal permeability on thymic ageing. Together, these findings establish a novel mechanism by which gut barrier dysfunction drives systemic activation of the immune system during ageing through thymic involution. This enhances our understanding of drivers of T cell ageing and opens up the possibility for the use of microbiome\u2010based interventions to restore immune homeostasis and promote healthy ageing in older adults.<\/jats:p>","DOI":"10.1111\/acel.14401","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T22:25:44Z","timestamp":1731709544000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Age\u2010related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing"],"prefix":"10.1111","volume":"24","author":[{"given":"Jessica","family":"Conway","sequence":"first","affiliation":[{"name":"Institute of Inflammation and Ageing University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N.","family":"De Jong","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"White","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Dugan","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nia Paddison","family":"Rees","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia M.","family":"Parnell","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E.","family":"Lamberte","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection University of Birmingham  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Sharma\u2010Oates","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Mauro","sequence":"additional","affiliation":[{"name":"Institute of Inflammation and Ageing University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"van Schaik","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection University of Birmingham  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Anderson","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M. 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