Login to Access Video or Poster Abstract: MP42-09
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 atrophic changes in urethral sphincter muscles are recognized as the most common cause for UI in the geriatric population. Recently, atrogin (a muscle-specific E3 ubiquitin ligase) is recognized as an important molecular pathway involved in age-related muscle atrophy. We tested the hypothesis that increased urethral sphincter atrophy during advanced aging is mediated by this novel atrogin pathway._x000D_ _x000D_

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 /atrophy in rabbits. We employed young (6-9 months), middle age (>12 months) and old rabbits (>30 months) and measured urethral muscle thickness (using transurethral ultrasound (US) technique (Fig A-inset) as well as urethral closure pressure (Fig A) in response to pelvic floor muscle electrical stimulation. We harvested bladder neck (for lissosphincter) and mid-urethra (for rhabdosphincter) samples to evaluate protein and mRNA levels of atrogin (marker of atrophy) using Western blot (protein) /qPCR studies respectively.

Results

Our rabbit studies confirmed age-related changes in the urethral sphincter muscle thickness (Fig A) and alterations in closure pressure (Fig A) as well as in protein/mRNA levels of marker of atrophy (atrogin; Fig B-D) in both bladder neck and mid-urethra . These observations confirm our hypothesis that age-related increase in atrophy mediated via atrogin pathway may contribute to sphincter muscle dysfunction.

Conclusions

Our physiological, imaging and molecular studies are consistent with our hypothesis that age-related increase in atrogin protein contribute to sphincter muscle dysfunction. Targeting atrogin may be a novel approach to prevent age-related urethral sphincter muscle atrophy.

Funding

VA Rehabilitation Research Merit Award