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Changes in neuromuscular structure and functions of human colon during ageing are region-dependent

Broad, John; Kung, Victor W. S.; Palmer, Alexandra; Elahi, Shezan; Karami, Azadeh; Darreh-Shori, Taher; Ahmed, Shafi; Thaha, Mohamed Adhnan; Carroll, Rebecca; Chin-Aleong, Joanne; Martin, Joanne E.; Saffrey, M. Jill; Knowles, Charles H. and Sanger, Gareth John (2019). Changes in neuromuscular structure and functions of human colon during ageing are region-dependent. Gut, 68(7) pp. 1210–1223.

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Objective: To determine if human colonic neuromuscular functions decline with increasing age.

Design: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups.

Results: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI ), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthaseimmunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/gtissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon.

Conclusion: In ascending not descending colon, ageing impairs cholinergic function.

Item Type: Journal Item
Copyright Holders: 2019 The Author
ISSN: 1468-3288
Project Funding Details:
Funded Project NameProject IDFunding Body
Loss of neuromuscular functions of the large bowel during advanced age: characterisation of regionally-dependent mechanisms of action and clinical impact382/1114 to GJS,CHK&MJSDunhill Medical Trust
Keywords: ageing; axon transport; choline acetyltransferase; colon; human
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Research Group: Health and Wellbeing PRA (Priority Research Area)
Item ID: 56680
Depositing User: Jill Saffrey
Date Deposited: 26 Sep 2018 14:07
Last Modified: 01 Jul 2019 19:39
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