Changes in the enteric nervous system and surrounding cells during ageing

The enteric nervous system continues to undergo changes throughout life. Changes in both enteric neurons and glial cells in old age have been reported, but our understanding both of the effects of described changes on gastrointestinal function and the causes of age-related changes are poorly understood. We are analysing changes in the enteric nervous system and surrounding cells in the intestine of the C57/Bl6 mouse during ageing, using a multidisciplinary approach. We are focusing on the large intestine and terminal bowel; regions that are implicated in changes that may contribute to the increased incidence of constipation and incontinence in the elderly population. The progression of age-associated changes is studied by analysing tissues from animals at 3, 12, 18 and 24 months of age. Changes in the numbers and phenotypic properties of neurons and nerve fibre density and also changes in Interstitial cells, fibroblast-like cells and enteroendocrine cells are being studied in both tissue sections and whole mount preparations by immunohistochemistry, confocal and electron microscopy. Physiological and pharmacological analysis of tissues is also performed and the combined data from all these types of approach allows us to understand more fully how ageing affects neural and non-neural regulation of gut functions. Our data show that changes in the responses of the distal colon, rectum and internal anal sphincter in vitro occur during ageing, and that these changes are complex, involve several different signalling systems and do not simply relate to changes in cell number. In addition, we are investigating the mechanisms that cause age-related changes in both neurons and non-neural cells in the intestine, using a combination of markers and imaging techniques. Our preliminary data indicate that the different cell types involved in the regulation of gastrointestinal motility may be differentially affected during ageing. A detailed understanding of ageing of the ENS and surrounding cells will provide valuable information to increase our understanding of age-associated gastrointestinal dysfunction