{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:50:44Z","timestamp":1792525844174,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE032101"],"award-info":[{"award-number":["R03DE032101"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE034787"],"award-info":[{"award-number":["R03DE034787"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE034757"],"award-info":[{"award-number":["R01DE034757"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accumulation of senescent cells is increasingly recognized as a mechanism of aging and is considered an attractive therapeutic target for various age\u2010associated diseases. The prevalence and severity of periodontitis increase with age, and preclinical studies have demonstrated that senescent cells could be a potential therapeutic target for age\u2010associated periodontitis. However, clinical data linking cellular senescence and periodontitis are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Gingival tissues affected with periodontitis and healthy controls were collected from patients with or without periodontitis in a cross\u2010sectional study. RNA isolated from these samples was analyzed for senescence gene expression by quantitative polymerase chain reaction (qPCR) assays. The associations of the gene expression levels with periodontal diagnosis, presence or absence of attachment loss or bleeding on probing, and age were examined. Additionally, we analyzed the expression of senescence genes in the gingival tissues of mice with or without ligature\u2010induced periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 54 human gingival tissue samples were included in the study. Among the genes analyzed,\n                      <jats:italic>p16<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>MMP2<\/jats:italic>\n                      , and\n                      <jats:italic>MMP14<\/jats:italic>\n                      exhibited significantly higher expression in the periodontitis group compared to the control group. Furthermore, these genes were associated with clinical signs of periodontitis, such as bleeding score and attachment loss at diagnosis. There were no statistically significant positive correlations between gene expression levels and age. The ligature\u2010induced periodontitis significantly increased expression levels of\n                      <jats:italic>p16<\/jats:italic>\n                      and other senescence genes in mouse gingival tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gene expression analysis indicates the accumulation of senescent cells in gingival tissue affected with periodontitis, supporting the concept that senotherapeutics could be effective in treating periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>\n                      Biological stressors cause cells to age, known as cellular senescence. These senescent cells play a significant role in age\u2010related diseases and are considered a key target for treatment. Periodontitis, a gum disease, damages the tissues that support teeth and is a leading cause of tooth loss worldwide. When people get older, they have a higher chance of being affected by periodontitis. Studies using animal models have shown that the accumulation of senescent cells may be driving periodontitis in older individuals. Therefore, targeting senescent cells may be a potential treatment approach for periodontitis. However, clinical evidence showing the accumulation of senescent cells in gum tissue affected with periodontitis is limited. This study aimed to investigate whether periodontitis is accompanied by senescent cell accumulation in the gum tissue by examining gene expression in tissues with and without periodontitis. A total of 54 human gum tissues (27 healthy and 27 diseased) were collected during gum surgeries. Our analysis found that four genes related to cellular senescence (\n                      <jats:italic>p16<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>MMP2<\/jats:italic>\n                      , and\n                      <jats:italic>MMP14<\/jats:italic>\n                      ) were significantly higher in samples affected with periodontitis. This indicates that senescent cells accumulate in diseased gum tissue. Additionally, results from an animal experiment suggested that being affected with gum disease may be a mechanism accelerating cellular aging in the gum tissue. The findings support the concept that targeting senescent cells would be an effective approach to treat gum disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.11393","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:15:41Z","timestamp":1760706941000},"page":"747-759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Upregulation of senescence\u2010associated gene expression levels in human gingival tissue affected by periodontitis"],"prefix":"10.1002","volume":"97","author":[{"given":"Su Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Periodontology Indiana University School of Dentistry  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandni","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Periodontology Indiana University School of Dentistry  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Department of Oral Biology Dental College of Georgia  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hamada","sequence":"additional","affiliation":[{"name":"Section of Periodontics University of California Los Angeles School of Dentistry  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Applied Sciences Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University School of Medicine and Richard M. Fairbanks School of Public Health  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanchit","family":"John","sequence":"additional","affiliation":[{"name":"Department of Periodontology Indiana University School of Dentistry  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Kittaka","sequence":"additional","affiliation":[{"name":"Department of Oral Biology Dental College of Georgia  Augusta Georgia USA"},{"name":"Department of Cellular Biology and Anatomy Medical College of Georgia  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.015"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00314-w"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnae010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13083"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI180558"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI173371"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03096-2"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.140520"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552491"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20-0529"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.115220"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54318"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-017-9994-6"},{"issue":"20","key":"e_1_2_10_17_1","first-page":"S1","article-title":"A new classification scheme for periodontal and peri\u2010implant diseases and conditions \u2013 Introduction and key changes from the 1999 classification","volume":"45","author":"Caton JG","year":"2018","journal-title":"J Periodontol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-022-02583-7"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1588-2"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.070159"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-1-30"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13558"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4897"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10352"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3882"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345241255325"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12939"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.16-0517"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0035-4"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46746-2"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80452-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05388-4"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345241299789"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207441"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17144923"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01145-5"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12432"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.04.005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.03.028"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI154888"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-024-01968-w"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155360"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.822816"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10335-5"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00776-z"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.012"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69958"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2005.00786.x"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.06.036"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2002"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08181"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316981"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.006"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jper.11393","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jper.11393","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jper.11393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:18:49Z","timestamp":1781511529000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1002\/jper.11393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jper.11393"],"URL":"https:\/\/doi.org\/10.1002\/jper.11393","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"2025-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}