Aging and gastrointestinal neuromuscular function: insights from within and outside the gut

Understanding the effects of aging on the gut neuromuscular axis is of growing and profound importance in light of demographic data demonstrating a steady increase in the aged population globally. Likely areas of significant importance include the potential effects of aging on the extrinsic and intrinsic innervations, smooth muscle function in the human colon, and determination of whether specific biomarkers can be identified in the gut neural plexi, ICC, glial cells or smooth muscle that predict the onset of neurodegeneration. Age-related neuronal losses occur in both the myenteric plexus and submucosal plexus. In general, these losses start in adulthood and progress during the lifespan and involve cholinergic neurons predominately. Parallel age-dependent loss of enteric glia is also observed. The drop-out of these cell populations follows an oral-anal gradient, with greater losses noted distally. Dystrophic axonal swelling and dilated varicosities also increase in an age-dependent manner in the extrinsic innervations (vagal, DRG and sympathetic pathways), as well as, nitrergic neurons in the gut. Advanced age is associated with increased oxidative stress and mitochondrial dysfunction at the cellular level, culminating in disequilibrium between cytoprotective and cytotoxic pathways favoring the latter. Caloric restriction and/or diets supplemented with specific nutrients may help attenuate the effects of aging on neuromuscular function.