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aging causes conditions including periodontal disease. We investigated how the sugar alcohol erythritol, which has anti-caries effects, impacts aging periodontal tissues and gingival fibroblasts in mice and humans in vivo and in vitro. Mice were classified into three groups: control groups of six-week-old (YC) and eighteen-month-old mice (AC) and a group receiving 5% w\/w erythritol water for 6 months (AE). After rearing, RNA was extracted from the gingiva, and the levels of aging-related molecules were measured using PCR. Immunostaining was performed for the aging markers p21, \u03b3H2AX, and NF-\u03baB p65. p16, p21, \u03b3H2AX, IL-1\u03b2, and TNF\u03b1 mRNA expression levels were higher in the gingiva of the AC group than in the YC group, while this enhanced expression was significantly suppressed in AE gingiva. NF-\u03baB p65 expression was high in the AC group but was strongly suppressed in the AE group. We induced senescence in cultured human gingival fibroblasts using H2O2 and lipopolysaccharide before erythritol treatment, which reduced elevated senescence-related marker (p16, p21, SA-\u03b2-gal, IL-1\u03b2, and TNF\u03b1) expression levels. Knockdown of PFK or PGAM promoted p16 and p21 mRNA expression, but erythritol subsequently rescued pyruvate production. Overall, intraoral erythritol administration may prevent age-related oral mucosal diseases.<\/jats:p>","DOI":"10.3390\/nu15184050","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T23:17:20Z","timestamp":1695165440000},"page":"4050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Erythritol Can Inhibit the Expression of Senescence Molecules in Mouse Gingival Tissues and Human Gingival Fibroblasts"],"prefix":"10.3390","volume":"15","author":[{"given":"Haruna","family":"Yokoi","sequence":"first","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"},{"name":"Department of Geriatric Oral Science, Graduate School of Dentistry, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5674-0671","authenticated-orcid":false,"given":"Masae","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Aoki","sequence":"additional","affiliation":[{"name":"Research Department, Daiichi Sankyo Healthcare Co., Ltd., Tokyo 140-8710, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Resmi","family":"Raju","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoriko","family":"Ikuyo","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"},{"name":"Section of Community Oral Health and Epidemiology, Division of Oral Health, Technology and Epidemiology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"},{"name":"Department of Operative Dentistry, School of Dentistry, Aichi Gakuin University, Nagoya 464-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Shikama","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"},{"name":"Department of Geriatric Oral Science, Graduate School of Dentistry, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2402-8633","authenticated-orcid":false,"given":"Kenji","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Oral Disease Research, Geroscience Research Center, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan"},{"name":"Department of Geriatric Oral Science, Graduate School of Dentistry, Tohoku University, Sendai 980-8575, Japan"},{"name":"Section of Community Oral Health and Epidemiology, Division of Oral Health, Technology and Epidemiology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41574-020-0335-y","article-title":"The role of cellular senescence in ageing and endocrine disease","volume":"16","author":"Khosla","year":"2020","journal-title":"Nat. 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