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Studies have revealed the relationship between periodontal disease and the oral microbiota; however, the impact of periodontal disease on the expression of senescence markers and on the inflammaging of the oral and systemic microbiome remains unclear. We hypothesized that aging increases the periodontitis\u2010induced changes in the oral and systemic microbiome and is accompanied by an altered inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Experimental periodontitis was induced in 18\u2010month\u2010old (old) and 8\u2010month\u2010old (young) C57BL\/6 mice by placing ligatures around the second maxillary molars. Bone morphometric analyses were conducted to assess bone loss. Senescence\u2010 and inflammatory\u2010related gene expression in the gingiva was measured by quantitative polymerase chain reaction (qPCR). Serum inflammatory markers were evaluated via immunoassay. Oral, brain, and gut microbial content were analyzed using next\u2010generation sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Maxillary bone loss was significantly higher in the old mice with periodontal disease than in young mice. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. The alpha diversity of the oral and brain microbial communities differed significantly between old and young mice.\n                      <jats:italic>Treponema denticola<\/jats:italic>\n                      ,\n                      <jats:italic>Fusobacterium nucleatum, Porphyromonas gingivalis, P. pasteri<\/jats:italic>\n                      , and\n                      <jats:italic>Prevotella nigrescens<\/jats:italic>\n                      were only detected in the brains of old animals with periodontitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Periodontopathogens and oral commensals are either only found in the brains of old animals with periodontal disease or are more prevalent in the brains of old animals, suggesting that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Aging may increase the periodontitis\u2010induced changes in the oral and systemic microbiome, which an altered inflammatory response may accompany. Experimental periodontitis was created in old and young mouse models. Bone loss, senescence, and inflammatory gene expression and serum inflammatory markers were assessed in each model, and oral, brain, and gut microbial content was analyzed. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. Our results suggested that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70118","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:16:31Z","timestamp":1776089791000},"page":"1965-1979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aging and periodontitis increase brain dissemination of oral bacteria"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-5925","authenticated-orcid":false,"given":"Ozge","family":"Unlu","sequence":"first","affiliation":[{"name":"The ADA Forsyth Institute  Cambridge Massachusetts USA"},{"name":"Department of Medical Microbiology Istanbul Atlas University Faculty of Medicine Istanbul 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