Abstract

Ageing is associated with impaired neuromuscular function of the terminal gastrointestinal (GI) tract, which can result in chronic constipation, faecal impaction and incontinence. Interstitial cells of cajal (ICC) play an important role in regulation of intestinal smooth muscle contraction. However, changes in ICC volume with age in the terminal GI tract (the anal canal including the anal sphincter region and rectum) have not been studied. Here, the distribution, morphology and network volume of ICC in the terminal GI tract of 3‐ to 4‐month‐old and 26‐ to 28‐month‐old C57BL/6 mice were investigated. ICC were identified by immunofluorescence labelling of wholemount preparations with an antibody against c‐Kit. ICC network volume was measured by software‐based 3D volume rendering of confocal Z stacks. A significant reduction in ICC network volume per unit volume of muscle was measured in aged animals. No age‐associated change in ICC morphology was detected. The thickness of the circular muscle layer of the anal sphincter region and rectum increased with age, while that in the distal colon decreased. These results suggest that ageing is associated with a reduction in the network volume of ICC in the terminal GI tract, which may influence the normal function of these regions.

Highlights

  • Impaired function of the terminal bowel is common in the elderly and can result in chronic constipation, faecal impaction and incontinence, reducing quality of life.[1]

  • As in other parts of the gut, movement of contents along the terminal bowel occurs as a result of co‐ordinated activity of intestinal smooth muscle, which is regulated by the enteric nervous system and by two specialised types of stromal cells: interstitial cells of cajal (ICC)[5] and PDGFRα+ve, referred to as Telocytes, or fibroblast‐like

  • The present study is the first to investigate the effects of age on ICC populations in the mouse terminal bowel

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Summary

Introduction

Impaired function of the terminal bowel is common in the elderly and can result in chronic constipation, faecal impaction and incontinence, reducing quality of life.[1] Previous studies have described changes in the innervation and smooth muscle of the ageing gut,[2] but analysis of changes in other cell types involved in regulation of smooth muscle motility in the terminal bowel (ie the anal sphincter region, or ASR, rectum and distal colon) is limited. As in other parts of the gut, movement of contents along the terminal bowel occurs as a result of co‐ordinated activity of intestinal smooth muscle, which is regulated by the enteric nervous system and by two specialised types of stromal cells: interstitial cells of cajal (ICC)[5] and PDGFRα+ve (platelet‐derived growth factor receptor alpha‐positive cells), referred to as Telocytes, or fibroblast‐like

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