Ageing and gastrointestinal sensory function: altered colonic mechanosensory and chemosensory function in the aged mouse

Abstract

Key points Remarkably little is known about how age affects the sensory signalling pathways in the gastrointestinal tract despite age‐related gastrointestinal dysfunction being a prime cause of morbidity amongst the elderly populationHigh‐threshold gastrointestinal sensory nerves play a key role in signalling distressing information from the gut to the brain.We found that ageing is associated with attenuated high‐threshold afferent mechanosensitivity in the murine colon, and associated loss of TRPV1 channel function.These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease. AbstractAgeing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood. Here we investigated the effect of age upon gastrointestinal sensory signalling pathways in order to address the mechanisms underlying these changes. In vitro mouse colonic and jejunal preparations with attached splanchnic and mesenteric nerves were used to study mechanosensory and chemosensory afferent function in 3‐, 12‐ and 24‐month‐old C57BL/6 animals. Quantitative RT‐PCR was used to investigate mRNA expression in colonic tissue and dorsal root ganglion (DRG) cells isolated from 3‐ and 24‐month animals, and immunohistochemistry was used to quantify the number of 5‐HT‐expressing enterochromaffin (EC) cells. Colonic and jejunal afferent mechanosensory function was attenuated with age and these effects appeared earlier in the colon compared to the jejunum. Colonic age‐related loss of mechanosensory function was more pronounced in high‐threshold afferents compared to low‐threshold afferents. Chemosensory function was attenuated in the 24‐month colon, affecting TRPV1 and serotonergic signalling pathways. High‐threshold mechanosensory afferent fibres and small‐diameter DRG neurons possessed lower functional TRPV1 receptor responses, which occurred without a change in TRPV1 mRNA expression. Serotonergic signalling was attenuated at 24 months, but TPH1 and TPH2 mRNA expression was elevated in colonic tissue. In conclusion, we saw an age‐associated decrease in afferent mechanosensitivity in the mouse colon affecting HT units. These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease.

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel

“…In a recent study from our laboratory the effect of aging on mouse afferent nerve sensitivity was measured. We found that aging correlated with a reduction in sensory firing and altered serotonergic signaling . A similar decline in afferent sensitivity was also observed for the human bowel although sample size was limited by the availability of tissue.…”

“…Experimental studies with rodents have shown that the numbers of myenteric and submucosal neurones decline with age, and that sympathetic innervation and vagal nerves deteriorate . A recent study from our laboratory found that mechanosensation and serotonergic chemosensitvity in the mouse intestine was significantly inhibited with age . However, there are currently no equivalent human data showing how aging affects sensory signaling from the bowel.…”

“…10 A recent study from our laboratory found that mechanosensation and serotonergic chemosensitvity in the mouse intestine was significantly inhibited with age. 11 However, there are currently no equivalent human data showing how aging affects sensory signaling from the bowel. The interplay between mast cells, enterochromaffin (EC) cells, and the sensory innervation of the gut wall is a key to normal neuro-immune signaling.…”

Stress–strain analysis of duodenal contractility in response to flow and ramp distension in rabbits fed low‐fiber diet

“…It is well known that the gastrointestinal tract contains intrinsic and extrinsic enteric neurons, smooth muscle cells, and interstitial cells of Cajal (ICC), which respond to mechanical deformations by altering transmembrane ionic currents in a process called mechanoelectrical coupling . It has been demonstrated that factors such as aging and diabetes change the mechanosensitivity. Furthermore, it has been reported that enteric neurons were affected by malnutrition .…”

Editorial

“…Ageing is also associated with changes in sensory function, which is highlighted here in relation to mechanosensory and chemosensory function in the gut (Keating et al . ) that contribute to gastrointestinal dysfunction and morbidity.…”