{"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":1790273308766,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"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","award":["BB\/GO15147\/1"],"award-info":[{"award-number":["BB\/GO15147\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/GO15988\/1"],"award-info":[{"award-number":["BB\/GO15988\/1"]}],"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":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age\u2010related changes in nitric oxide and acetylcholine release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Nitrergic relaxation increased between 3 and 6\u00a0months, peaked at 12\u00a0months and declined in the 18 and 24\u00a0months groups. These changes were in part explained by an age\u2010related decrease in nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h) release and a compensatory decrease in cholinesterase activity. Age\u2010related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h, <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>, sodium nitroprusside or <jats:styled-content style=\"fixed-case\">KC<\/jats:styled-content>l. Similarly, there was no change in basal tension developed by the anorectum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>The decrease in nitrergic signaling with increasing age may contribute to the age\u2010related fecal impaction and constipation previously described in this model by partially obstructing defecation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13426","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T05:15:04Z","timestamp":1533014104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Changes in murine anorectum signaling across the life course"],"prefix":"10.1111","volume":"30","author":[{"given":"S.","family":"Fidalgo","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Science Centre for Stress and Age\u2010Related Disease University of Brighton  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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