Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics.

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2024-12-07 DOI:10.1111/acel.14399
Iman M Al-Naggar, Maria Antony, Dylan Baker, Lichao Wang, Lucas Da Cunha Godoy, Chia-Ling Kuo, Matthew O Fraser, Phillip P Smith, Ming Xu, George A Kuchel
{"title":"Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics.","authors":"Iman M Al-Naggar, Maria Antony, Dylan Baker, Lichao Wang, Lucas Da Cunha Godoy, Chia-Ling Kuo, Matthew O Fraser, Phillip P Smith, Ming Xu, George A Kuchel","doi":"10.1111/acel.14399","DOIUrl":null,"url":null,"abstract":"<p><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-related 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-induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high-fat 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-induced 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-blood barrier.</p>","PeriodicalId":119,"journal":{"name":"Aging Cell","volume":" ","pages":"e14399"},"PeriodicalIF":8.0000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/acel.14399","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

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-related 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-induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high-fat 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-induced 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-blood barrier.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信