{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T07:23:07Z","timestamp":1772090587539,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study compared host responses against natural gingivitis in the gingival crevicular fluid (GCF) in young and aged periodontium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This cross-sectional study recruited two patient populations with natural gingivitis in young (18\u201335 years old) and elder cohorts (36\u201375 years old). GCF samples were analyzed for 39 inflammatory and tissue remodeling mediators using bead-based multiplex immunoassays. Independent t-tests with false discovery rate adjustments were used to compare mediator expressions between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty patients were enrolled in these comparisons, including young patients (n=22) and elder patients (n=18). In comparison with the young group, the elder group had greater clinical attachment loss and higher expression of MPO (p&amp;lt;0.001), IL-1\u03b2 (p&amp;lt;0.05), IL-6 (p&amp;lt;0.05), and IL-8 (p&amp;lt;0.05). Despite the ratio of MMP-8\/TIMP-1 being not significantly different (p&amp;gt;0.05), the young group had greater ratio of MMP-9\/TIMP-1 than old group (p&amp;lt;0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The current findings reveal that the inflammatory profiles of young and elder cohorts with natural gingivitis are distinct. The young cohort with natural gingivitis demonstrated lower disease susceptibility and more robust tissue turnover, whereas the aged periodontium was characterized by higher susceptibility to disease and diminished healing capacity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1761707","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:55:16Z","timestamp":1772088916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of aging on host responses in gingival crevicular fluid in natural gingivitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yung-Ting","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Periodontics, University of Washington School of Dentistry","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan Y.","family":"An","sequence":"additional","affiliation":[{"name":"Department of Oral Health Science, University of Washington School of Dentistry","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnny","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Oral Health Science, University of Washington School of Dentistry","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Daubert","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University of Washington School of Dentistry","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard P.","family":"Darveau","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University of Washington School of Dentistry","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2012.00148","article-title":"A new definition of aging","volume":"3","author":"Flatt","year":"2012","journal-title":"Front Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11010058","article-title":"Effect of aging on homeostasis in the soft tissue of the periodontium: a narrative review","volume":"11","author":"Kim","year":"2021","journal-title":"J Pers Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/prd.12135","article-title":"Aging, inflammation, immunity and periodontal disease","volume":"72","author":"Ebersole","year":"2016","journal-title":"Periodontol 2000"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.24-0715","article-title":"Gingival crevicular fluid during experimental gingivitis: A review of immune and tissue regulation","volume":"96","author":"Hsu","year":"2025","journal-title":"J Periodontol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509340148","article-title":"Effect of age on gingival crevicular fluid concentrations of MIF and PGE2. Effect of age on gingival crevicular fluid concentrations of MIF and PGE2","volume":"88","author":"Nonnenmacher","year":"2009","journal-title":"J Dent Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2174\/1874210601004010013","article-title":"The effect of age on the gingival crevicular fluid composition during experimental gingivitis. A pilot study","volume":"1","author":"Tsalikis","year":"2010","journal-title":"Open Dent J"},{"key":"B7","first-page":"5","article-title":"Crevicular fluid levels of interleukin-1alpha and interleukin-1beta during experimental gingivitis in young and old adults","volume":"4","author":"Tsalikis","year":"2002","journal-title":"J Int Acad Periodontol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.1999.260707.x","article-title":"Differences in the inflammatory response in young and old human subjects during the course of experimental gingivitis","volume":"26","author":"Fransson","year":"1999","journal-title":"J Clin Periodontol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12366","article-title":"Primary prevention of periodontitis: managing gingivitis","volume":"42","author":"Chapple","year":"2015","journal-title":"J Clin Periodontol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0157","article-title":"A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification","volume":"89","author":"Caton","year":"2018","journal-title":"J Periodontol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.157001","article-title":"American Academy of Periodontology Task Force report on the update to the 1999 classification of periodontal diseases and conditions","volume":"86","year":"2015","journal-title":"J Periodontol"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1002\/JPER.17-0719","article-title":"Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Chapple","year":"2018","journal-title":"J Periodontol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jocd.2014.04.086","article-title":"The American Society of Anesthesiologists (ASA) Physical Status Classification System is an independent determinant of long-term mortality in older patients with hip fracture: systematic review and meta-analysis of longitudinal studies","volume":"3","author":"Haentjens","year":"2014","journal-title":"J Clin Densitom"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3109\/00016356408993968","article-title":"Periodontal disease in pregnancy. Ii. Correlation between oral hygiene and periodontal condtion","volume":"22","author":"Silness","year":"1964","journal-title":"Acta Odontol Scand"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/00016356309011240","article-title":"Periodontal disease in pregnancy. I. Prevalence and severity","volume":"21","author":"Loe","year":"1963","journal-title":"Acta Odontol Scand"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.23-0692","article-title":"Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health","volume":"95","author":"Hsu","year":"2024","journal-title":"J Periodontol"},{"key":"B17","volume-title":"R: A Language and Environment for Statistical Computing","year":"2024"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J Open Source software"},{"key":"B19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1996.tb00561.x","article-title":"The effect of age on the development of gingivitis: Clinical, microbiological and histological findings","volume":"23","author":"Fransson","year":"1996","journal-title":"J Clin Periodontol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060264","article-title":"Case definitions for use in population-based surveillance of periodontitis","volume":"78","author":"Page","year":"2007","journal-title":"J Periodontol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1754-4505.2009.00082.x","article-title":"Effects of human aging on periodontal tissues","volume":"29","author":"Huttner","year":"2009","journal-title":"Spec Care Dentist"},{"key":"B23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/prd.12136","article-title":"The subgingival periodontal microbiota of the aging mouth","volume":"72","author":"Feres","year":"2016","journal-title":"Periodontol 2000"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515625962","article-title":"Effect of aging on periodontal inflammation, microbial colonization, and disease susceptibility","volume":"95","author":"Wu","year":"2016","journal-title":"J Dent Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12675","article-title":"Age-related changes in immune function (immune senescence) in caries and periodontal diseases: a systematic review","volume":"44","author":"Preshaw","year":"2017","journal-title":"J Clin Periodontol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512457373","article-title":"Prevalence of periodontitis in adults in the United States: 2009 and 2010","volume":"91","author":"Eke","year":"2012","journal-title":"J Dent Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1902\/jop.2014.140364","article-title":"Periodontitis and glycemic control in diabetes: NHANES 2009 to 2012","volume":"86","author":"Garcia","year":"2015","journal-title":"J Periodontol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(94)00088-6","article-title":"Interleukin-8 and the chemokine family","volume":"17","author":"Baggiolini","year":"1995","journal-title":"Int J Immunopharmacol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/froh.2021.689475","article-title":"Clinically healthy human gingival tissues show significant inter-individual variability in GCF chemokine expression and sub-gingival plaque microbial composition","volume":"14","author":"Bamashmous","year":"2021","journal-title":"Front Oral Health"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1995.66.10.852","article-title":"Levels of interleukin-1 beta and interleukin-8 in gingival crevicular fluids in adult periodontitis","volume":"66","author":"Tsai","year":"1995","journal-title":"J Periodontol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2004.00744.x","article-title":"The investigation of glutathione peroxidase, lactoferrin, myeloperoxidase and interleukin-1beta in gingival crevicular fluid: implications for oxidative stress in human periodontal diseases","volume":"39","author":"Wei","year":"2004","journal-title":"J Periodontal Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2220\/biomedres.34.31","article-title":"Enhancement of gingival inflammation induced by synergism of IL-1\u03b2 and IL-6","volume":"34","author":"Sawada","year":"2013","journal-title":"BioMed Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4172","DOI":"10.1038\/ncomms5172","article-title":"Chronic inflammation induces telomere dysfunction and accelerates ageing in mice","volume":"5","author":"Jurk","year":"2014","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.622950","article-title":"Interleukin-6 knockout inhibits senescence of bone mesenchymal stem cells in high-fat diet-induced bone loss","volume":"11","author":"Li","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3390\/cells11030359","article-title":"Interconnections between inflammageing and immunosenescence during ageing","volume":"11","author":"Teissier","year":"2022","journal-title":"Cells"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01563.x","article-title":"Salivary MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis","volume":"37","author":"Gursoy","year":"2010","journal-title":"J Clin Periodontol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2010.10.021","article-title":"Salivary levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1: A pilot study about the relationship with periodontal status and MMP-9\u2013 1562C\/T gene promoter polymorphism","volume":"56","author":"Isaza-Guzm\u00e1n","year":"2011","journal-title":"Arch Oral Biol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"555","DOI":"10.3109\/08820139.2013.822766","article-title":"The role of cytokines in inflammatory bone loss","volume":"42","author":"Souza","year":"2013","journal-title":"Immunol Invest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"Armitage","year":"","journal-title":"Ann Periodontol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1761707\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:55:18Z","timestamp":1772088918000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1761707\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2026.1761707"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1761707","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"article-number":"1761707"}}