Award details

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

ReferenceBB/G015988/1
Principal Investigator / Supervisor Dr Margaret Saffrey
Co-Investigators /
Co-Supervisors
Dr Richard Ranson
Institution Open University
DepartmentLife, Health & Chemical Sciences
Funding typeResearch
Value (£) 357,096
StatusCompleted
TypeResearch Grant
Start date 01/10/2009
End date 31/03/2013
Duration42 months

Abstract

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 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. 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.

Summary

In the ageing population, terminal bowel dysfunction, manifest as faecal incontinence, which is often linked with faecal impaction, is very common and a significant cause of illness. Normal bowel function and defecaetion depend upon a combination of voluntary and involuntary actions of the muscles regulating bowel function. These processes, in turn, depend upon the structural integrity and the normal molecular and physiological properties of the complex system of nerves, muscles and secretory cells 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 therefore to use a multi-disciplinary approach, bringing together expertise from four academics, to fully characterise the physiological, molecular and structural age-associated changes in the cells of the terminal colon, rectum and anal sphincters. The work will be performed in mice, for a number of reasons; mice have a life-span amenable to studies on ageing; many of the variables associated with studies on humans can be avoided; 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 age-associated incontinence and faecal impaction to be developed
Committee Closed Committee - Animal Sciences (AS)
Research TopicsAgeing, Neuroscience and Behaviour
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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