Integrated analysis of the impact of age-associated neuronal and enteroendocrine changes on normal bowel functions

In the ageing population, terminal bowel dysfunction, manifest as faecal incontinence, often linked with faecal impaction, is very common and a significant cause of morbidity.

Normal bowel function and defecaetion depend upon a combination of voluntary and involuntary actions of the muscles regulating bowel function: autonomic and sensory reflexes in the terminal colon, rectum and internal anal sphincter, and voluntary control of the external anal sphincter and pelvic floor muscles. These processes, in turn, depend upon the structural integrity and the normal molecular, neurochemical and physiological properties of the nervous, enteroendocrine and muscular systems that together make up this part of the digestive tract.

Many cells and tissues are known to undergo structural and molecular changes during ageing that result in changes to their functional properties. Little is known however, of the changes that occur in the cells of the terminal bowel during ageing.

The aim of the proposed project is to use a multi-disciplinary approach, bringing together expertise from four academics, to fully characterise the physiological, molecular, neurochemical and ultrastructural age-associated changes in the smooth and striated sphincteric muscles, intrinsic autonomic innervation and enteroendocrine systems of the terminal colon, rectum and anal sphincters.

The work will be performed in mice because mouse gastrointestinal physiology is well-understood and readily analysed and in future, research based on the data obtained from this project will be able to employ the powerful tool of mouse genetics to further analyse the changes that occur in ageing terminal bowel. The results of this work will allow more effective therapies for the treatment of incontinence and faecal impaction to be developed.