Micturition defects and altered bladder function in the klotho mutant mouse model of aging.

INTRODUCTION AND OBJECTIVES Symptoms associated with detrusor underactivity (DU) or underactive bladder (UAB) can severely impact a person's quality of life, and growing old is the main etiological factor of DU and UAB. The gene Klotho has been associated with suppression of several aging phenotypes, and there is moderate klotho expression in the bladder. Given this, we hypothesized that the klotho gene is involved in regulation of bladder function. Thus, we examined a premature aging rodent genetic model with hypomorphic klotho expression for alterations in bladder function. METHODS Klotho mutant mice are established as a preclinical model of aging. Male and female klotho mice had micturition measured at weeks 4, 6, and 8 through metabolic cage and void spot assays. Histology was assessed at 4, 6, and 8 weeks. Lastly, bladder contraction was assessed using bladder strip tissue bath. All animals were gender- and age-matched with wild-type littermates for analysis. RESULTS Void spot and bladder contraction assays revealed that klotho mutant mice, similar to other aging models, have increased voiding frequency and decreased voiding volume per micturition event. The in vitro contractile response to electrical stimulation was weaker and muscarinic receptor subtype expression was reduced in the in klotho mutant mouse bladders. These data suggest that klotho mutant mouse bladders had impaired bladder function. CONCLUSIONS Klotho mutant mice recapitulate many characteristics of an older dysfunctional bladder, including altered bladder function. Given the short time frame to bladder dysfunction and robustness of the model, this model will provide new insights to drive aging bladder research.