Language
English
Publication Date
2-1-2026
Journal
Aging Cell
DOI
10.1111/acel.70391
PMID
41577484
PMCID
PMC12830083
PubMedCentral® Posted Date
1-23-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Aging leads to a progressive decline in overall bladder function resulting in lower urinary tract symptoms and increased susceptibility to infections. However, tissue-specific mechanisms of aging, specifically the contributions of the urothelium, remain elusive. Here, we introduce mouse bladder epithelium-derived organoids (mBEDOs) as a scalable platform to model urothelial aging. mBEDOs from aged mice recapitulate key features of age-associated cellular reprogramming, including oxidative stress, senescence, and DNA damage. We demonstrate the utility of mBEDOs for modeling Uropathogenic Escherichia coli (UPEC) infection, generating assembloids between mBEDOs and macrophages to model epithelial-immune interactions, and genetic perturbation. Using the mBEDO platform, we also identify urothelium-specific changes in purine, amino acid, and glycerophospholipid metabolism, which may contribute to age-associated cellular perturbations. Lastly, supplementation with depleted metabolites, nicotinamide and d-mannose, reduces DNA damage and oxidative stress and restores mitochondrial integrity in aged mBEDOs. These findings establish mBEDOs as an effective platform for investigating molecular and cellular underpinnings of urothelial aging and exploring metabolism-based interventions for age-associated bladder dysfunction.
Keywords
Animals, Mice, Organoids, Urothelium, Aging, Oxidative Stress, Uropathogenic Escherichia coli, DNA Damage, Urinary Bladder, Mice, Inbred C57BL, Escherichia coli Infections, Cellular Senescence
Published Open-Access
yes
Recommended Citation
Parab, Adwaita R; Salazar, Arnold M; Bark, Steven J; et al., "A Scalable Organoid Model of Urothelial Aging for Metabolic Interrogation, Infection Modeling, and Reversal of Age-Associated Changes" (2026). Faculty, Staff and Students Publications. 6462.
https://digitalcommons.library.tmc.edu/baylor_docs/6462