Impaired colonic motility and reduction in tachykinin signalling in aged mouse

Patel, Bhavik Anil; Patel, Nikkita; Fidalgo, Sara; Wang, Chunfang; Ranson, Richard N.; Saffrey, M. Jill and Yeoman, Mark S. (2014). Impaired colonic motility and reduction in tachykinin signalling in aged mouse. Experimental Gerontology, 53 pp. 24–30.



Aging is associated with an increased incidence of constipation in humans. The contribution that the aging process makes to this condition is unclear. The aim of this study was to determine the effects of age on fecal output and colonic motility in male C57BL/6J mice and to determine the role that altered tachykinin signaling plays in this process. Total fecal output recorded over a 24 hour period decreased with age due to a reduction in the number of pellets produced and their water content. These changes occurred in the absence of any significant change in food and water intake. There was an increase in the amount of fecal matter stored in the isolated colon with age which caused a proportional increase in colonic length. Analysis of colonic motility using an artificial pellet demonstrated that pellets moved in a stepwise fashion through the colon. There was an age-related increase in pellet transit time due to decreases in the step distance, velocity, and frequency of stepwise movements. These changes were reversed using the neurokinin 2 (NK2) receptor agonist neurokinin A. Addition of the NK2 receptor antagonist GR159897 significantly increased transit time in the young animals by decreasing step distance, velocity and frequency, but was without effect in the aged colon. In summary, the aging C57BL/6J mouse shows an constipation impaired motility phenotype and consistent with that seen in a large proportion of elderly humans. These effects appear, at least in part, to be due to an attenuation of tachykinin signaling via NK2 receptors.

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