Effects of age on signalling and function in the lower bowel

The incidence of chronic constipation and faecal impaction increases with age and often leads to social isolation and a loss of independence and therefore quality of life. This problem is estimated to affect one  in five community dwelling older people and up to 80 per cent of institutionalised older people. The causes of age-related constipation are likely to be multi-factorial with changes in nutrition, mobility and polypharmacy as well as the ageing process being contributory factors. This BBSRC funded project used a pre-clinical model to examine the specific contributions that the ageing process makes to chronic constipation.

Project timeframes

The project began in 2010 and is ongoing.

Project aims

The aim of the project was

  • to characterise the age-related changes in signalling processes and function in the lower bowel.
  • to understand the contribution that processes such as stress, inflammation and replicative senescence play in the observed changes.
  • to identify novel targets and interventions that can be tested in the clinic to alleviate this debilitating condition.

Project findings and impact

The project found that ageing is associated with alterations in mucosal serotonin signalling, colonic tachykinin signalling and decreases in colonic motility and faecal pellet output. These effects are not due to neurodegeneration but are linked with increases in the expression of inflammatory mediators and some can be reversed using the anti-TNFalpha drug, etanercept.

We have also demonstrated that the density of some nerve fibres that innervate the internal anal sphincter are reduced with age and that a range of compensatory changes are required to ensure that this muscle does not lose function. Together these data are starting to provide a range of targets that could be used to help alleviate a range of bowel disorders in older people.

Research team

Dr Mark Yeoman

Dr Bhavik Patel

Yukyee Woo

Output

Parmar L, Fidalgo S, Yeoman MS, Patel BA. Chromatographic analysis of age-related changes in mucosal serotonin transmission in the murine distal ileum. Chem Cent J. 2012 Apr 11;6(1):31

Changes in the innervation of the mouse internal anal sphincter during aging

By:Wang, C; Houghton, MJ; Gamage, PPKM; Collins,; Patel,; Yeoman, MS; Ranson, RN; Saffrey, MJ. Neurogastroenterology and Motility Volume: 25 Issue: 7 Pages: e469-e477, 2013.

Age-Related Changes in Melatonin Release in the Murine Distal Colon. Diss, LB; Robinson, SD; Wu, Y; Fidalgo, S; Yeoman,; Patel, ACS Chemical Neuroscience Volume: 4 Issue: 5 Pages: 879-887, 2013.

Myenteric neuron numbers are maintained in aging mouse distal colon. Gamage, P; Ranson, RN; Yeoman, MS; Patel, BA; Saffrey, MJ. Neurogastroenterology and Motility 25:e495-505, 2013.

Impaired Colonic Motility and reduction in tachykinin signalling in the aged mouse. Bhavik Anil Patel, Nikkita Patel, Sara Fidalgo, Chunfang Wang, Richard N. Ranson, M. Jill Saffrey and Mark S. Yeoman. Exp. Gerontol. 53: 24-30, 2014.

Partners

Dr M.J Saffrey, Department of Life, Health and Chemical Sciences, Open University.

Dr Richard Ranson, Department of Applied Sciences, University of Northumbria.

Dr Joyce Wang, Department of Life, Health and Chemical Sciences, Open University.