The aging bladder phenotype is not the direct consequence of bladder aging

Abstract

Aims The prevalence of urinary dysfunction increases with age, yet therapies are often suboptimal. Incomplete understanding of the linkages between system, organ, and tissue domains across lifespan remains a knowledge gap. If tissue‐level changes drive the aging bladder phenotype, parallel changes should be observed across these domains. In contrast, a lack of inter‐domain correlation across age groups would support the hypothesis that urinary performance is a measure of the physiologic reserve, dependent on centrally‐mediated adaptive mechanisms in the aging system. Methods Male and female mice across four age groups underwent sequential voiding spot assays, pressure/flow cystometry, bladder strip tension studies, histology, and quantitative PCR analyses. The primary objective of this study was to test the impact of age on the cortical, autonomic, tissue functional and structural, and molecular domains, and identify inter‐domain correlations among variables showing significant changes with age within these domains. Results Behavior revealed diminished peripheral voiding and spot size in aged females. Cystometry demonstrated increased postvoid residual and loss of volume sensitivity, but the preservation of voiding contraction power, with almost half of oldest‐old mice failing under cystometric stress. Strip studies revealed no significant differences in adrenergic, cholinergic, or EFS sensitivity. Histology showed increased detrusor and lamina propria thickness, without a change in collagen/muscle ratio. Adrb2 gene expression decreased with age. No consistent inter‐domain correlations were found across age groups. Conclusions Our findings are consistent with a model in which centrally‐mediated adaptive failures to aging stressors are more influential over the aging bladder phenotype than local tissue changes.

Stretch‐ and carbachol‐induced ATP release from bladder wall preparations of young and aged mice

“…Active and passive properties of mouse bladder wall preparations. Intact detrusor strips from aged mice were less contractile to EFS or carbachol stimulation in agreement with some studies, 19 but at variance with others that reported either no change, 20 or even enhanced contractile function. 21 There was also no evidence for functional detrusor denervation in aged mice as the decline of EFS and agonist-induced responses in aged mice were similar (T carb /T max,EFS similar, Table 1), and the extent of atropine resistance was also the same.…”

“…The overall implication is that data from aged animals does not represent a homogeneous group and that comorbid conditions may overwhelm any effect of age per se, 20 and if translated to elderly humans would underlie their variable incidence of urinary urgency. One direct hypothesis that may be tested is that when ATP release is much greater in some aged animals or humans, so also should afferent activity as a pathophysiological basis of increased urgency.…”

Evaluation of urodynamics parameters in different age and incontinence group of women

“…In a recent study, the effect of aging on urodynamic parameters has been assessed among women with stress urinary incontinence (SUI) with a mean age of 57 years [14]. They found that Qmax, voided volume and Pdet@Qmax decreased and PVR and desire to void increased significantly with age after 60 years [10]. We also found a weak negative correlation between Pdet and age.…”

“…The cause of urethral dysfunction is hypothesized as decreased synthesis of NO, a molecule that relaxes urethral smooth muscle [21], and increased synthesis of the endogenous inhibitor of NO-synthase, with age [22]. Another recent animal study showed that the consistency of layer thickness and nuclear density of the bladder wall structure in mice is preserved following maturation, but this may differ in humans [10]. A correlation between urethral pressure and estrogen levels during the menstrual cycle is expected.…”

“…The prevalence of aging-related diseases has been increasing, due to declining birth rate and mortality, and increasing life expectancy [10]. Urodynamically proven detrusor overactivity (DO) becomes much more common in old age, making it challenging to distinguish purely age-related changes in the bladder, from those due to DO.…”