D-Mannose reduces cellular senescence and NLRP3/GasderminD/IL-1β-driven pyroptotic uroepithelial cell shedding in the murine bladder.

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combating stress, and decreased regenerative capacity. Multiple diseases, including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying the impact of aging on the urinary tract mucosa and the correlation between aging and disease remain poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with reduced acid phosphatase activity and decreased overall autophagic flux in the aged urothelium, indicative of compromised cellular homeostasis.

Supraphysiologic Vaginal Estrogen Therapy in Aged Mice Mitigates Age-Associated Bladder Inflammatory Response to Urinary Tract Infections.

Importance: Bladder diseases characterized by chronic inflammation are highly prevalent in older women, as are recurrent urinary tract infections (rUTIs). Recurrent urinary tract infections lead to chronic inflammation of the bladder mucosa and cause lower urinary tract symptoms that persist even after the infection is cleared. Vaginal estrogen therapy (VET) has long been used for the treatment of rUTIs; however, its mechanism of action remains unclear.