MP42-09 ATROGIN IS A NOVEL MARKER OF AGE-RELATED URETHRAL SPHINCTER MUSCLE ATROPHY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2017MP42-09 ATROGIN IS A NOVEL MARKER OF AGE-RELATED URETHRAL SPHINCTER MUSCLE ATROPHY M. Raj Rajasekaran, Johnny Fu, My-Uyen (Lilly) Nguyen, and Valmik Bhargava M. Raj RajasekaranM. Raj Rajasekaran More articles by this author , Johnny FuJohnny Fu More articles by this author , My-Uyen (Lilly) NguyenMy-Uyen (Lilly) Nguyen More articles by this author , and Valmik BhargavaValmik Bhargava More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1298AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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. 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. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e547 Advertisement Copyright & Permissions© 2017MetricsAuthor Information M. Raj Rajasekaran More articles by this author Johnny Fu More articles by this author My-Uyen (Lilly) Nguyen More articles by this author Valmik Bhargava More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...