Login to Access Video or Poster Abstract: MP42-17
Sources of Funding: VA Rehabilitation Research Merit Award

Introduction

Previous studies show an age-related increase in the prevalence of urinary incontinence (UI) (10-15% in adults and ~30% % in older population >70 years). Age-related degenerative changes to urethral sphincter muscles are recognized as the most common cause for UI in the geriatric population. Recently, Wntβ catenin signaling pathway is recognized as the major molecular pathway involved in age-related skeletal muscle fibrosis. We tested the hypothesis that increased urethral sphincter fibrosis during advanced aging is mediated by a novel Wnt-β catenin signaling pathways.

Methods

We used a rabbit model to establish time course of age-related urethral sphincter muscle complex dysfunction and for further evaluation of molecular mechanisms of muscle dysfunction /fibrosis in rabbits. We employed (n=3) young (6-9 months), middle age (>12 months) and old rabbits (>30 months) and harvested mid-urethra (for rhabdosphincter) samples to evaluate protein and mRNA levels of markers of fibrosis using Western blot (protein) /qPCR (mRNA) studies respectively. _x000D_ _x000D_

Results

Our rabbit studies confirmed age-related changes in alterations in closure pressure as well as in protein/mRNA levels of markers of fibrosis (β-catenin, collagen-I, and TGF-β etc; Fig A-C). These observations confirm our hypothesis that age-related increase in fibrogenic proteins mediated via Wntβ catenin signaling pathways may contribute to sphincter muscle dysfunction. _x000D_ _x000D_

Conclusions

Our physiological and molecular studies are consistent with our hypothesis that age-related increase in fibrogenic proteins contribute to sphincter muscle function. Targeting Wnt signaling pathway may be beneficial in preventing sphincter muscle fibrosis.

Funding

VA Rehabilitation Research Merit Award