{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:47:03Z","timestamp":1785818823155,"version":"3.56.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>5-methyltetrahydrofolate (5-MTHF), the biologically active form of folate, possesses well-characterized anti-inflammatory and antioxidant properties that are closely implicated in the regulation of cellular senescence. Accordingly, this study aimed to investigate whether 5-MTHF attenuates periodontitis by mitigating cellular senescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 to evaluate the association between serum 5-MTHF levels and periodontitis. Weighted multivariable regression models were applied, and exploratory mediation analysis assessed the contribution of biological aging. In vitro experiments examined the anti-senescence effect of 5-MTHF on lipopolysaccharide (LPS)-induced human gingival fibroblasts (HGFs). An in vivo mouse model of experimental periodontitis was used to evaluate alveolar bone loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 6,245 adults, higher serum 5-MTHF levels were significantly associated with lower odds of periodontitis, reduced clinical attachment loss, and shallower probing depth. Biological aging mediated 5.5%\u201317.3% of these associations. Mechanistically, 5-MTHF treatment attenuated LPS-induced cellular senescence in HGFs, as shown by decreased SA-\u03b2-gal activity, downregulation of p16, p21, and senescence-associated secretory phenotype genes. Correspondingly, local administration of 5-MTHF significantly alleviated alveolar bone resorption in mice with periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>5-MTHF is associated with improved periodontal health, partly through attenuating cellular senescence. Our findings suggest that targeting senescence with 5-MTHF may represent a novel mechanism-based strategy for preventing and treating periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1851692","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:28:13Z","timestamp":1785817693000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting senescence with 5-methyltetrahydrofolate: a novel strategy to attenuate periodontitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Lisa","family":"Yang","sequence":"first","affiliation":[{"name":"School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Hunan University of Medicine, Huaihua","place":["Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Li","sequence":"additional","affiliation":[{"name":"Liaoning 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