{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:08:28Z","timestamp":1790273308703,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T00:00:00Z","timestamp":1723939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increasing age increases the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to this phenotype is unclear. This study explored the effects of age on key motility patterns in the murine colon and determined the contribution that altered neurokinin 2 (NK<jats:sub>2<\/jats:sub>) \u2010mediated signaling made to the aging phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mucosal reflexes, colonic migrating motor complexes (CMMCs) and colonic motility assays were explored in isolated ex\u00a0vivo colons from 3, 12\u201314, 18\u2010 and 24\u2010months old mice and the NK<jats:sub>2<\/jats:sub>\u2010mediated response determined. Electrical field stimulation (EFS) or exogenous drug application were used to explore the role of the mucosa in colonic segments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Aging reduced the force of contraction of the distal colon mucosal reflex, the frequency and force of contraction of CMMCs and the NK<jats:sub>2<\/jats:sub>\u2010mediated component of both motility patterns. Ondansetron, a 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist, blocked a component of both motility patterns in full thickness but not in mucosa\u2010free segments of the distal colon. 5, hydroxytryptamine (5\u2010HT) and EFS\u2010evoked NK<jats:sub>2<\/jats:sub>\u2010dependent contractions were reduced with increasing age. Smooth muscle sensitivity to 5\u2010HT or neurokinin A (NKA) was not altered with age. In isolated colon motility assays application of NKA decreased transit time in 24\u2010months colon and the NK<jats:sub>2<\/jats:sub> antagonist GR159897 increased transit times in both 3\u2010 and 24\u2010months old colons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Aging impairs key motility patterns in the murine colon. These changes involve a decrease in mucosally\u2010evoked NK<jats:sub>2<\/jats:sub>\u2010mediated signaling. Targeting NK<jats:sub>2<\/jats:sub>\u2010mediated signaling may provide a novel approach to treating age\u2010related motility disorders in the lower bowel.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14891","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T04:44:05Z","timestamp":1724042645000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Decreases in mucosally\u2010evoked tachykinin signaling pathways can explain age\u2010related reductions in murine colonic motility patterns"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2113-8650","authenticated-orcid":false,"given":"Mark S.","family":"Yeoman","sequence":"first","affiliation":[{"name":"Centre for Lifelong Health, School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Fidalgo","sequence":"additional","affiliation":[{"name":"Centre for Lifelong Health, School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"India","family":"Hobby","sequence":"additional","affiliation":[{"name":"Centre for Lifelong Health, School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Hafeez","sequence":"additional","affiliation":[{"name":"Centre for Lifelong Health, School of Applied Sciences University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel N.","family":"Ranson","sequence":"additional","affiliation":[{"name":"Department of Applied Sciences, Faculty of Health &amp; Life Sciences Northumbria University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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