Enteric neurodegeneration in ageing.
The objective of this article is to review the clinical presentation and neurobiology of degeneration of the enteric nervous system with emphasis on human data where available. Constipation, incontinence and evacuation disorders are frequently encountered in the ageing population. Healthy lower gastrointestinal function is essential for successful ageing as it is critical to maintaining independence and autonomy to pursue further activity. One clinical expression of enteric neurodegeneration is constipation. However, the aetiology may be multifactorial as disturbances of epithelial, muscle or neural function may all result from neurodegeneration. There is evidence of loss of excitatory (e.g. cholinergic) enteric neurons and interstitial cells of Cajal, whereas inhibitory (including nitrergic) neurons appear unaffected. Understanding neurodegeneration in the enteric nervous system is key to developing treatments to reverse it. Neurotrophins have been shown to accelerate colonic transit and relieve constipation in the medium term; they are also implicated in maintenance programmes in adult enteric neurons through a role in antioxidant defence. However, their effects in ageing colon require further study. There is evidence that 5-HT(2) and 5-HT(4) mechanisms are involved in development, maintenance and survival of enteric neurons. Further research is needed to understand and potentially reverse enteric neurodegeneration.