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ORIGINAL RESEARCH article
Front. Physiol.
Sec. Gastrointestinal Sciences
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1540465
Aging-related impairment of neurogenic chloride secretion in human colon mucosa
Provisionally accepted- 1 Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- 2 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Elderly individuals are more susceptible to chronic constipation, which may be linked to imbalanced mucosa secretion and absorption. Our research aims to explore the agerelated alterations in epithelial chloride secretion within the human colon.Colonic mucosal tissues were obtained from 9 young patients (aged 28-35 years), 10 middle-aged patients (aged 48-56 years), 10 elderly patients without constipation (aged 66-75 years), and 12 elderly patients with constipation (aged 65-78 years) who underwent surgery for colonic carcinoma. The epithelial chloride (Cl -) secretion was assessed using the short-circuit current (Isc) method. Comparative analysis was conducted on Cl -secretion induced by spontaneous activity, bethanechol, forskolin, veratridine, and electrical field stimulation (EFS) in the four groups. Additionally, investigations were carried out on changes in cholinergic and VIPergic Cl -secretion.The spontaneous Cl -secretion was not affected by aging. The increase in Isc induced by bethanechol and forskolin remained unaltered in aged colon. However, the veratridine-induced neurogenic Isc increment were significantly reduced with aging and constipation. The EFS-evoked Isc rising, which typically exhibiting a biphasic pattern, was inhibited by aging in a frequency-dependent manner. Administration of scopolamine and VIP6-28 to block cholinergic and vasoactive intestinal peptide (VIP) receptors led to smaller increases in the first and second phases of the EFS-evoked response in aged colons compared to young colons.Significant impairments in neurogenic Cl -secretion occur in the aged colon, correlating with the degeneration of cholinergic and VIPergic nerves in the mucosa. This study could enhance our understanding of the pathophysiology of elderly constipation.
Keywords: Aging, intestinal epithelium, chloride secretion, elderly constipation, enteric neurodegeneration CFTR, cystic fibrosis transmembrane regulator, CaCC, Ca 2+ -activated chloride channel, ENaC, epithelial Na + channel, cAMP, cyclic adenosine monophosphate
Received: 14 Dec 2024; Accepted: 04 Mar 2025.
Copyright: © 2025 Wang, He, Yang, Bai, Song, Hou and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing He, Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Lei Zhang, Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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