{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:58:40Z","timestamp":1788422320200,"version":"build-2803163510"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Br. J. Biomed. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The G protein-coupled receptor 68 (GPR68) detects variations in extracellular pH, and has potential roles in homeostasis and responses to ischaemia and inflammation within different organs, including the gastrointestinal tract. However, in the human colon the distribution of GPR68 remains unclear. We examined the localization and density of GPR68 within the ascending (AC) and descending (DC) human colon from younger and older adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Macroscopically normal AC and DC were obtained from patients undergoing lower bowel cancer resection (aged 22\u201391 years; grouped into younger (\u226460 years) and older (\u226567 years) populations). Immunolabelling was performed using formalin-fixed, paraffin-embedded sections and antibodies against GPR68, protein gene product 9.5 (PGP9.5) and calretinin to identify the presence and density of GPR68-immunoreactive (IR) expressing cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ageing did not change the density of total PGP9.5-IR enteric neuronal fibres in the AC or DC. For the myenteric plexus (MP) of both age groups, the densities of calretinin-IR neurons were similar in both the AC (younger: 1.2 \u00b1 0.3 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ; older: 0.9 \u00b1 0.2 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      per mm\n                      <jats:sup>2<\/jats:sup>\n                      plexus) and DC (1.4 \u00b1 0.2 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ; 1.3 \u00b1 0.3 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      per mm\n                      <jats:sup>2<\/jats:sup>\n                      plexus), but reduced in the mucosa of older adults for both AC (respectively, 9.8 \u00b1 0.5 vs. 3.2 \u00b1 0.1\/pixel) and DC (11.5 \u00b1 0.9 vs. 7.4 \u00b1 0.3\/pixel). Similar reduction of calretinin-IR enteric neurons was found in the SMP of AC but not clearly in the DC in the older adults. GPR68 was widely expressed in the mucosa, circular muscle and myenteric plexus of both the AC and DC. The density of GPR68-IR in the muscle and myenteric plexus was similar in both age groups, but smaller in the mucosa of older adults for both AC and DC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GPR68 is widely distributed within the enteric nervous system of the human colon, with potential roles for GPR68 suggested in the muscle and MP, and in the functions of calretinin-IR neurons within the mucosa. Further, the concomitant loss of GPR68 and calretinin-IR neurons in the mucosa of older adults suggests selective vulnerability of mucosal sensory and homeostatic mechanisms of the ageing colon.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/bjbs.2026.15884","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:10:16Z","timestamp":1775538616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Related Loss of GPR68 and Calretinin Immunoreactive Neurons Within the Mucosa, Not the Myenteric Plexus of Human Colon"],"prefix":"10.3389","volume":"83","author":[{"given":"Nicholas","family":"Baidoo","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Westminster","place":["London, United Kingdom"]},{"name":"Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"De Rasis","sequence":"additional","affiliation":[{"name":"Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London","place":["London, United Kingdom"]},{"name":"Department of Pharmacy, Health Science and Nutrition, University of Calabria","place":["Rende, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Paine","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Bulmer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J.","family":"Sanger","sequence":"additional","affiliation":[{"name":"Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1016\/j.gtc.2007.07.013","article-title":"Constipation: Evaluation and Treatment of Colonic and Anorectal Motility Disorders","volume":"36","author":"Rao","year":"2007","journal-title":"Gastroenterol Clinics North America"},{"key":"B2","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s12876-015-0366-3","article-title":"Chronic Constipation in the Elderly: A Primer for the Gastroenterologist","volume":"15","author":"De Giorgio","year":"2015","journal-title":"BMC Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1055\/s-2007-1021212","article-title":"Brief Physical Inactivity Prolongs Colonic Transit Time in Elderly Active Men","volume":"14","author":"Liu","year":"1993","journal-title":"Int Journal Sports Medicine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.bpg.2009.09.001","article-title":"Constipation in Old Age","volume":"23","author":"Gallagher","year":"2009","journal-title":"Best Practice and Research. 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