Aging-related impairment of neurogenic chloride secretion in human colon mucosa

BACKGROUND: lderly individuals are more susceptible to chronic constipation, which may be linked to imbalanced mucosa secretion and absorption. Our research aims to explore the age-related alterations in epithelial chloride secretion within the human colon. METHODS: 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. RESULTS: 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. CONCLUSION: 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.