Age Related External Anal Sphincter Muscle Dysfunction & Fibrosis: Possible Role of Wnt-β Catenin Signaling Pathways.

Abstract

Studies show an age-related increase in the prevalence of anal incontinence and sphincter muscle atrophy. Wnt-β catenin signaling pathway has been recently recognized as the major molecular pathway involved in the age-related skeletal muscle atrophy and fibrosis. The goals of our study were to evaluate: (i) impact of normal aging on the EAS muscle length-tension (L-T) function & morphology; and (ii) specifically examine the role of Wnt signaling pathways in anal sphincter muscle fibrosis. New Zealand White female rabbits (six young 6 months old and six old 36 months of age were anesthetized anal canal pressure was measured to determine the L- T function of EAS. Animals were sacrificed at the end of study and anal canal was harvested and processed for histochemical studies (Masson trichrome stain for muscle /connective tissue) as well as for molecular markers known to induce fibrosis and atrophy (collagen-I, β-catenin, TGF- β, atrogin-1 and MURF-1). The L-T was significantly impaired in older animals compared to young animals. Anal canal sections stained with trichrome showed a significant decrease in the muscle content (52% in old compared to 70% in young) and an increase in the connective tissue/collagen content in the old animals. An increased protein and mRNA expression of all the fibrosis markers were seen in the older animals. Aging EAS muscle exhibits impairment of function and increase in connective tissue. Up regulation of atrophy and pro-fibrogenic proteins with aging may be the reason for the age-related decrease in anal sphincter muscle thickness and its function.

DOI: 10.1152/ajpgi.00209.2017

Cite this paper

@article{Rajasekaran2017AgeRE, title={Age Related External Anal Sphincter Muscle Dysfunction & Fibrosis: Possible Role of Wnt-β Catenin Signaling Pathways.}, author={Mahadevan Raj Rajasekaran and Sadhana Kanoo and Johnny Fu and M. L. Nguyen and Valmik Bhargava and Ravinder K. Mittal}, journal={American journal of physiology. Gastrointestinal and liver physiology}, year={2017}, pages={ajpgi.00209.2017} }