10.7910/DVN/Y1A8XI Wolf-Johnston, Amanda Amanda Wolf-Johnston University of Pittsburgh Harvard Dataverse 2026 Medicine, Health and Life Sciences Birder, Lori Lori Birder University of Pittsburgh Wolf-Johnston, Amanda Amanda Wolf-Johnston University of Pittsburgh 2026-06-01 2026-06-02 29635210 47006869 55554 59111998 1292503890 47286693 application/zip application/zip application/vnd.openxmlformats-officedocument.spreadsheetml.sheet application/zip application/zip application/zip 1.0 Creative Commons CC0 1.0 Universal Public Domain Dedication. The urinary bladder urothelium is crucial for maintaining barrier and signaling functions of the urinary bladder. The urothelium is a metabolically demanding tissue and therefore is particularly susceptible to the impact of aging. Age-associated alterations include increased oxidative stress (e.g., increased ROS) and impaired mitochondrial function that collectively contribute to a high prevalence of bladder dysfunction in older individuals. Emerging evidence suggests that changes in levels/activity of the enzyme purine nucleoside phosphorylase (PNPase) contribute to the extent of oxidative injury, cellular damage and other biological hallmarks of aging. PNPase converts ‘tissue-protective’ purines- that reduce ROS- to ‘tissue-damaging’ purines- that increase ROS. The aim of this study was designed to elucidate whether the endogenous PNPase inhibitor, 8-aminoguanine (8-AG), mitigates bladder nerve damage and age-associated adverse cellular and molecular changes (lipid peroxidation, mitochondrial dysfunction, cellular senescence, malfunctioning autophagy). Studies applied molecular and analytical methods in aged Fischer 344 rat urothelium. Treatment with 8-AG markedly ameliorated age-related urothelial abnormalities, restoring many parameters to levels comparable to those observed in younger animals. These findings suggest that the deleterious effects of purine dysregulation extend to the bladder urothelium and can be attenuated via gerotherapeutic benefits of 8-AG. Article submission under review.