{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:11:58Z","timestamp":1791922318910,"version":"4.3.4"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The effect of ageing on total collagen content of human colon has been poorly investigated. The aim of this study was to determine if ageing altered total collagen content and distribution in the human colon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Macroscopically normal ascending colon was obtained at surgery from cancer patients (n = 31) without diagnosis of diverticular disease or inflammatory bowel disease. Masson\u2019s trichrome and Picrosirius red stains were employed to identify the total collagen content and distribution within the sublayers of the colonic wall for adult (22\u201360 years; 6 males, 6 females) and elderly (70 \u2013 91years; 6 males, 4 female) patients. A hydroxyproline assay evaluated the total collagen concentration for adult (30\u201364 years; 9 male, 6 female) and elderly (66\u201391 years; 8 male, 8 female) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      Histological studies showed that the percentage mean intensity of total collagen staining in the mucosa, submucosa and muscularis externa was, respectively, 14(1.9) %, 74(3.2) % and 12(1.5) % in the adult ascending colon. Compared with the adults, the total collagen fibres content was increased in the submucosa (mean intensity; 163.1 \u00b1 11.1 vs. 124.5 \u00b1 7.8;\n                      <jats:bold>\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:bold>\n                      &lt; 0.05) and muscularis externa (42.5 \u00b1 8.0 vs. 20.6 \u00b1 2.8;\n                      <jats:bold>\n                        <jats:italic>P<\/jats:italic>\n                      <\/jats:bold>\n                      &lt; 0.01) of the elderly patients. There was no change in collagen content of the mucosa. The total collagen concentration was increased in the elderly by 16%. Sex-related differences were not found, and data were combined for analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Greater total collagen content was found in the submucosa and muscularis externa of the elderly human male and female colon. These changes may contribute to a possible loss of function with ageing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0269689","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T13:28:43Z","timestamp":1655472523000},"page":"e0269689","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":40,"title":["Total collagen content and distribution is increased in human colon during advancing age"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-2287","authenticated-orcid":true,"given":"Nicholas","family":"Baidoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie","family":"Crawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Knowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J.","family":"Sanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9113-006X","authenticated-orcid":true,"given":"Abi","family":"Belai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"issue":"6","key":"pone.0269689.ref001","doi-asserted-by":"crossref","first-page":"575","DOI":"10.23736\/S0026-4806.17.05417-9","article-title":"Gastrointestinal tract disorders in the elderly","volume":"108","author":"M Durazzo","year":"2017","journal-title":"Minerva Med"},{"key":"pone.0269689.ref002","doi-asserted-by":"crossref","first-page":"6757524","DOI":"10.1155\/2019\/6757524","article-title":"Gastrointestinal Tract Disorders in Older Age","volume":"2019","author":"I Dumic","year":"2019","journal-title":"Can J Gastroenterol Hepatol"},{"issue":"5","key":"pone.0269689.ref003","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2019.12.034","article-title":"Mechanisms, Evaluation, and Management of Chronic Constipation","volume":"158","author":"AE Bharucha","year":"2020","journal-title":"Gastroenterology"},{"key":"pone.0269689.ref004","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12877-015-0162-5","article-title":"Fecal impaction: a systematic review of its medical complications","volume":"16","author":"B Serrano Falc\u00f3n","year":"2016","journal-title":"BMC Geriatr"},{"issue":"2","key":"pone.0269689.ref005","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2036.2007.03376.x","article-title":"The burden of constipation on quality of life: results of a multinational survey","volume":"26","author":"A Wald","year":"2007","journal-title":"Aliment Pharmacol Ther"},{"issue":"4","key":"pone.0269689.ref006","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s40273-018-0609-6","article-title":"Cost Effectiveness of Treatments for Chronic Constipation: A Systematic Review","volume":"36","author":"D Han","year":"2018","journal-title":"Pharmacoeconomics"},{"issue":"9","key":"pone.0269689.ref007","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/j.1532-5415.2000.tb04793.x","article-title":"Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people","volume":"48","author":"M Camilleri","year":"2000","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"pone.0269689.ref008","doi-asserted-by":"crossref","first-page":"a004978","DOI":"10.1101\/cshperspect.a004978","article-title":"The collagen family","volume":"3","author":"S. Ricard-Blum","year":"2011","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"2","key":"pone.0269689.ref009","doi-asserted-by":"crossref","first-page":"G459","DOI":"10.1152\/ajpgi.2001.281.2.G459","article-title":"Viscoelastic properties of the human colon","volume":"281","author":"AE Bharucha","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"pone.0269689.ref010","doi-asserted-by":"crossref","first-page":"41436","DOI":"10.1038\/srep41436","article-title":"Intraluminal pressure patterns in the human colon assessed by high-resolution manometry","volume":"7","author":"JH Chen","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0269689.ref011","doi-asserted-by":"crossref","first-page":"021020","DOI":"10.1115\/1.2898712","article-title":"Biomechanical properties of abdominal organs in vivo and postmortem under compression loads","volume":"130","author":"J Rosen","year":"2008","journal-title":"J Biomech Eng"},{"issue":"10","key":"pone.0269689.ref012","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0021-9290(02)00084-2","article-title":"Mechanical properties of the human gastrointestinal tract","volume":"35","author":"VI Egorov","year":"2002","journal-title":"J Biomech"},{"issue":"3","key":"pone.0269689.ref013","doi-asserted-by":"crossref","first-page":"G349","DOI":"10.1152\/ajpgi.00127.2019","article-title":"Load-bearing function of the colorectal submucosa and its relevance to visceral nociception elicited by mechanical stretch","volume":"317","author":"S Siri","year":"2019","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"4","key":"pone.0269689.ref014","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/BF01649507","article-title":"Submucosal collagen changes in the normal colon and in diverticular disease","volume":"2","author":"HJ Thomson","year":"1987","journal-title":"Int J Colorectal Dis"},{"issue":"4","key":"pone.0269689.ref015","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/BF02054231","article-title":"Abnormal internal anal sphincter fibrosis and elasticity in fecal incontinence","volume":"38","author":"CT Speakman","year":"1995","journal-title":"Dis Colon Rectum"},{"issue":"12","key":"pone.0269689.ref016","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1007\/BF02553874","article-title":"Age and sex and anorectal manometry in incontinence","volume":"32","author":"P Enck","year":"1989","journal-title":"Dis Colon Rectum"},{"issue":"4","key":"pone.0269689.ref017","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s003840050094","article-title":"Effects of age on anal function in normal women","volume":"12","author":"AM Ryhammer","year":"1997","journal-title":"Int J Colorectal Dis"},{"issue":"9","key":"pone.0269689.ref018","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1532-5415.1984.tb02250.x","article-title":"Anorectal manometry in healthy elderly subjects","volume":"32","author":"V Loening-Baucke","year":"1984","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"pone.0269689.ref019","first-page":"50","article-title":"Effects of age and sex on anorectal manometry","volume":"80","author":"V Loening-Baucke","year":"1985","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"pone.0269689.ref020","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00341292","article-title":"Age-related alterations in the strength and collagen content of left colon in rats","volume":"7","author":"H Christensen","year":"1992","journal-title":"Int J Colorectal Dis"},{"issue":"7","key":"pone.0269689.ref021","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.tips.2011.03.009","article-title":"The translational value of rodent gastrointestinal functions: a cautionary tale","volume":"32","author":"GJ Sanger","year":"2011","journal-title":"Trends Pharmacol Sci"},{"issue":"10","key":"pone.0269689.ref022","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1369\/0022155414545787","article-title":"Picrosirius red staining: a useful tool to appraise collagen networks in normal and pathological tissues","volume":"62","author":"R Lattouf","year":"2014","journal-title":"J Histochem Cytochem"},{"issue":"12","key":"pone.0269689.ref023","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1111\/codi.13400","article-title":"The use of Masson\u2019s trichrome staining, second harmonic imaging and two-photon excited fluorescence of collagen in distinguishing intestinal tuberculosis from Crohn\u2019s disease","volume":"18","author":"H Mao","year":"2016","journal-title":"Colorectal Dis"},{"issue":"3","key":"pone.0269689.ref024","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1152\/physrev.1975.55.3.418","article-title":"Posttranslational protein modifications, with special attention to collagen and elastin","volume":"55","author":"PM Gallop","year":"1975","journal-title":"Physiol Rev"},{"issue":"11","key":"pone.0269689.ref025","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/nep.12321","article-title":"Qualitative and quantitative analysis of fibrosis in the kidney","volume":"19","author":"TD Hewitson","year":"2014","journal-title":"Nephrology (Carlton)"},{"issue":"1","key":"pone.0269689.ref026","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1136\/gut.37.1.91","article-title":"Cross linking of collagen is increased in colonic diverticulosis","volume":"37","author":"L Wess","year":"1995","journal-title":"Gut"},{"issue":"6","key":"pone.0269689.ref027","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1101\/pdb.prot073411","article-title":"Manual hematoxylin and eosin staining of mouse tissue sections","volume":"2014","author":"RD Cardiff","year":"2014","journal-title":"Cold Spring Harb Protoc"},{"issue":"12","key":"pone.0269689.ref028","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1136\/jclinpath-2013-201885","article-title":"Inflammatory bowel disease biopsies: updated British Society of Gastroenterology reporting guidelines","volume":"66","author":"British Society of Gastroenterology","year":"2013","journal-title":"J Clin Pathol"},{"key":"pone.0269689.ref029","first-page":"75","article-title":"Some histological methods: trichrome stainings and their preliminary technique","volume":"12","author":"PJ Masson","year":"1929","journal-title":"J Tech Methods"},{"issue":"4","key":"pone.0269689.ref030","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/BF01002772","article-title":"Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections","volume":"11","author":"LC Junqueira","year":"1979","journal-title":"Histochem J"},{"issue":"2","key":"pone.0269689.ref031","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1109\/TMI.2014.2361481","article-title":"Towards large-scale histopathological image analysis: hashing-based image retrieval","volume":"34","author":"X Zhang","year":"2015","journal-title":"IEEE Trans Med Imaging"},{"issue":"7","key":"pone.0269689.ref032","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"CA Schneider","year":"2012","journal-title":"Nat Methods"},{"issue":"1","key":"pone.0269689.ref033","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1186\/s12859-017-1934-z","article-title":"ImageJ2: ImageJ for the next generation of scientific image data","volume":"18","author":"CT Rueden","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"pone.0269689.ref034","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0003-2697(60)90050-6","article-title":"A specific method for the analysis of hydroxyproline in tissues and urine","volume":"1","author":"DJ PROCKOP","year":"1960","journal-title":"Anal Biochem"},{"issue":"7","key":"pone.0269689.ref035","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1136\/gutjnl-2018-316279","article-title":"Changes in neuromuscular structure and functions of human colon during ageing are region-dependent","volume":"68","author":"J Broad","year":"2019","journal-title":"Gut"},{"issue":"2","key":"pone.0269689.ref036","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/jcmm.12428","article-title":"An integrated assessment of histopathological changes of the enteric neuromuscular compartment in experimental colitis","volume":"19","author":"C Ippolito","year":"2015","journal-title":"J Cell Mol Med"},{"key":"pone.0269689.ref037","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-1-4939-8935-5_23","article-title":"Microtomy: Cutting Formalin-Fixed, Paraffin-Embedded Sections","volume":"1897","author":"J Sy","year":"2019","journal-title":"Methods Mol Biol"},{"key":"pone.0269689.ref038","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jmbbm.2013.02.016","article-title":"Microstructure-based constitutive modeling for the large intestine validated by histological observations","volume":"21","author":"DP Sokolis","year":"2013","journal-title":"J Mech Behav Biomed Mater"},{"key":"pone.0269689.ref039","unstructured":"Feng. B., Maier. F., Siri. S., Pierce. D.M. Quantifying the collagen-network morphology in mouse distal colon and rectum via nonlinear microscopy; Proceedings of the Biomedical Engineering Society 2019 Annual Fall Meeting; Philadelphia, PA, USA. pp. 16\u201319."},{"issue":"4","key":"pone.0269689.ref040","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000047841","article-title":"Morphology of isolated colonic crypts","volume":"168","author":"ME Robert","year":"2001","journal-title":"Cells Tissues Organs"},{"key":"pone.0269689.ref041","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-0897-4_3","article-title":"The enteric nervous system and gastrointestinal innervation: integrated local and central control","volume":"817","author":"JB Furness","year":"2014","journal-title":"Adv Exp Med Biol"},{"issue":"11","key":"pone.0269689.ref042","doi-asserted-by":"crossref","first-page":"e112466","DOI":"10.1371\/journal.pone.0112466","article-title":"Identification of different types of spinal afferent nerve endings that encode noxious and innocuous stimuli in the large intestine using a novel anterograde tracing technique","volume":"9","author":"NJ Spencer","year":"2014","journal-title":"PLoS One"},{"key":"pone.0269689.ref043","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1749-6632.2000.tb05225.x","article-title":"Neurotransmitters in neuronal reflexes regulating intestinal secretion","volume":"915","author":"HJ Cooke","year":"2000","journal-title":"Ann N Y Acad Sci"},{"issue":"9\u201310","key":"pone.0269689.ref044","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1023\/A:1019660519961","article-title":"Development and ageing of intestinal musculature and nerves: the guinea-pig taenia coli","volume":"30","author":"G Gabella","year":"2001","journal-title":"J Neurocytol"},{"issue":"1","key":"pone.0269689.ref045","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1113\/expphysiol.1985.sp002887","article-title":"Mechanical properties of the rat colon: the effect of age, sex and different conditions of storage","volume":"70","author":"DA Watters","year":"1985","journal-title":"Q J Exp Physiol"},{"issue":"8","key":"pone.0269689.ref046","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1177\/33.8.2410480","article-title":"A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections","volume":"33","author":"A L\u00f3pez-De Le\u00f3n","year":"1985","journal-title":"J Histochem Cytochem"},{"key":"pone.0269689.ref047","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.matbio.2016.09.001","article-title":"Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue","volume":"59","author":"A Gautieri","year":"2017","journal-title":"Matrix Biol"},{"key":"pone.0269689.ref048","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-981-13-2835-0_7","article-title":"Extracellular Matrix and Ageing","volume":"90","author":"HL Birch","year":"2018","journal-title":"Subcell Biochem"},{"issue":"2","key":"pone.0269689.ref049","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/15438600490277860","article-title":"Cross-linking in collagen by nonenzymatic glycation increases the matrix stiffness in rabbit achilles tendon","volume":"5","author":"GK Reddy","year":"2004","journal-title":"Exp Diabesity Res"},{"issue":"1","key":"pone.0269689.ref050","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ajg.2011.349","article-title":"Chronic constipation in the elderly","volume":"107","author":"JF Gallegos-Orozco","year":"2012","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"pone.0269689.ref051","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1476-5381.2012.02198.x","article-title":"Translational neuropharmacology: the use of human isolated gastrointestinal tissues","volume":"168","author":"GJ Sanger","year":"2013","journal-title":"Br J Pharmacol"},{"key":"pone.0269689.ref052","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1476-4598-13-46","article-title":"Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer","volume":"13","author":"R. Sanz-Pamplona","year":"2014","journal-title":"Molecular cancer"},{"issue":"1","key":"pone.0269689.ref053","doi-asserted-by":"crossref","first-page":"6359","DOI":"10.1038\/s41598-020-63368-y","article-title":"Altered organization of collagen fibers in the uninvolved human colon mucosa 10 cm and 20 cm away from the malignant tumor","volume":"10","author":"SZ Despotovi\u0107","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0269689.ref054","article-title":"Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function","volume":"15","author":"Alexandra Palmer","year":"2021","journal-title":"Frontiers in neuroscience"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269689","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T13:29:33Z","timestamp":1655472573000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269689"}},"subtitle":[],"editor":[{"given":"Amitava","family":"Mukherjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0269689","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,17]]}}}