Objective:

To examine the localization and density of GPR68 and calretinin-positive neurons in the ascending and descending human colon across different age groups (younger: ≤60 years, older: ≥67 years).

Key Findings:

• Total PGP9.5-IR enteric neuronal fibres density remained unchanged with age in both AC and DC.
• Calretinin-IR neurons showed reduced density in the mucosa of older adults compared to younger adults in both AC and DC.
• GPR68 was widely expressed in the mucosa, circular muscle, and myenteric plexus, with decreased density in the mucosa of older adults.

Interpretation:

The findings suggest that GPR68 and calretinin-IR neurons in the mucosa are selectively vulnerable to age-related decline, potentially impacting sensory and homeostatic functions in the colon, which may have clinical implications for managing age-related gastrointestinal disorders.

Limitations:

• The study focused only on patients undergoing bowel cancer resection, which may not represent the general population.
• The sample size and age group divisions may limit the generalizability of the findings.
• Potential biases in patient selection may affect the results.

Conclusion:

GPR68 is widely distributed in the enteric nervous system of the human colon, and the concurrent loss of GPR68 and calretinin-IR neurons in older adults indicates a potential decline in mucosal sensory mechanisms with age.