Diurnal Regulation of Urinary Behavior and Gene Expression in Aged Mice

Abstract Nocturia, defined as waking one or more times per night to urinate, is a prevalent and burdensome condition with few effective treatments. While the primary risk factor for nocturia is advanced age, few preclinical studies have addressed the pathophysiological mechanisms of nocturia in older subjects. Here, we develop a translational model of nocturia using aging mice and a behavioral paradigm that enables circadian assessment of voluntary urination in group-housed animals. We discovered dampened diurnal regulation of urinary behavior in aged mice compared to adult controls. Molecular analyses revealed disrupted diurnal expression of canonical circadian genes in aged mouse kidney and bladder tissues. Notably, we identified age-related loss of diurnal regulation of the bladder mechanosensory ion channel, Piezo1, suggesting a potential mechanism linking circadian disruption to altered bladder sensitivity. Our results reveal a role for circadian dysfunction in age-related nocturia and identify Piezo1 as a promising therapeutic target for chronobiological intervention.