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Mouse Bladder Wall Injection
Published on: July 12, 2011
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The aging bladder phenotype is not the direct consequence of bladder aging.
Cara C Hardy1,2,3, Spencer R Keilich1,4, Andrew G Harrison1,4
1Center on Aging, UConn Health, University of Connecticut SOM, Farmington, Connecticut.
Neurourology and Urodynamics
|August 28, 2019
Summary
Urinary dysfunction worsens with age, but central nervous system adaptive failures, not local tissue changes, appear to drive this aging bladder phenotype. This suggests therapies should focus on systemic adaptation rather than solely on bladder tissue.
Area of Science:
- Gerontology and Urology
- Physiology and Molecular Biology
Background:
- Urinary dysfunction prevalence increases with age, with current therapies often being suboptimal.
- A knowledge gap exists regarding the interplay between system, organ, and tissue domains across the lifespan in relation to aging bladder function.
- Understanding whether tissue-level changes or systemic adaptive mechanisms primarily influence the aging bladder phenotype is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the impact of aging on various domains: cortical, autonomic, tissue function/structure, and molecular.
- To identify correlations between age-related changes across these different domains in the bladder.
- To test the hypothesis that urinary performance reflects physiological reserve and centrally-mediated adaptations rather than solely local tissue changes.
Main Methods:
- Male and female mice across four age groups were studied.
- Evaluations included voiding spot assays, pressure/flow cystometry, bladder strip tension studies, histology, and quantitative PCR.
- The study aimed to correlate age-dependent variables across multiple biological domains.
Main Results:
- Aged female mice showed diminished peripheral voiding and spot size.
- Cystometry revealed increased post-void residual and reduced volume sensitivity, with many oldest-old mice failing under stress, despite preserved voiding contraction power.
- No significant differences in bladder strip sensitivity were found; histology showed increased detrusor and lamina propria thickness without altered collagen/muscle ratio. Adrb2 gene expression decreased with age, and no consistent inter-domain correlations were observed.
Conclusions:
- The aging bladder phenotype appears more influenced by failures in centrally-mediated adaptations to aging stressors than by local tissue changes.
- Findings support a model where systemic adaptive mechanisms, rather than intrinsic tissue alterations, are key determinants of age-related urinary dysfunction.
- This suggests a potential shift in therapeutic targets towards enhancing central adaptive capacities.
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