Cellular Senescence and SASP in Bladder Ageing: Mechanisms and Emerging Interventions

Bladder dysfunction is a prevalent age-related condition that severely impairs quality of life in older adults and commonly manifests as lower urinary tract symptoms (LUTS), including frequency, urgency, incontinence, and nocturia. Cellular senescence, characterized by irreversible cell-cycle arrest accompanied by persistent metabolic activity, is increasingly recognized as a contributor to age-associated tissue degeneration. Senescent cells secrete a diverse array of inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes, collectively termed the senescence-associated secretory phenotype (SASP), which can disrupt tissue homeostasis through autocrine and paracrine signaling. Yet the bladder remains relatively understudied, and evidence linking cellular senescence and SASP to bladder dysfunction is fragmented and predominantly preclinical. Key uncertainties concern cell-specific SASP sources, causality, bladder-specific biomarkers, and validation in human tissues. To address this gap, this review critically integrates and evaluates bladder-specific evidence across ageing-related dysfunction, radiation-induced bladder injury, chemotherapy-induced cystitis, and interstitial cystitis/bladder pain syndrome, while distinguishing direct mechanistic evidence from indirect or pathway-based associations. We further synthesize emerging senescence-targeted strategies, including senolytics and senomorphics, and highlight the context- and cell-dependent nature of therapeutic responses. By defining the current strength and limitations of the evidence and identifying key translational priorities, this review provides an integrated framework for understanding how cellular senescence and SASP may contribute to bladder dysfunction and for guiding the development of mechanism-based, biomarker-informed interventions.