{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:26:06Z","timestamp":1789025166416,"version":"build-2803163510"},"reference-count":93,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21 AG063528"],"award-info":[{"award-number":["R21 AG063528"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging\u2010related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy\u2010induced senescence in\u00a0vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high\u2010fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD\u2010induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine\u2010blood barrier.<\/jats:p>","DOI":"10.1111\/acel.14399","type":"journal-article","created":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T11:50:47Z","timestamp":1733572247000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-8934","authenticated-orcid":false,"given":"Iman M.","family":"Al\u2010Naggar","sequence":"first","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"},{"name":"Department of Cell Biology University of Connecticut Health  Farmington Connecticut USA"},{"name":"Department of Surgery University of Connecticut Health  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Antony","sequence":"additional","affiliation":[{"name":"The University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; Genome Sciences University of Connecticut Health  Farmington Connecticut USA"},{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Da Cunha","family":"Godoy","sequence":"additional","affiliation":[{"name":"The Cato T. Laurencin Institute for Regenerative Engineering  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4452-2380","authenticated-orcid":false,"given":"Chia\u2010Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"},{"name":"The Cato T. Laurencin Institute for Regenerative Engineering  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew O.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Research &amp; Development Durham Veterans Affairs Medical Centers  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"},{"name":"Department of Surgery University of Connecticut Health  Farmington Connecticut USA"},{"name":"Connecticut Institute for Brain and Cognitive Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4477-939X","authenticated-orcid":false,"given":"Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"},{"name":"Department of Genetics &amp; Genome Sciences University of Connecticut Health  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8387-7040","authenticated-orcid":false,"given":"George A.","family":"Kuchel","sequence":"additional","affiliation":[{"name":"Center on Aging University of Connecticut  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40610-020-00140-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073542"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2690"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040881"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","unstructured":"Baker D. 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