{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:33Z","timestamp":1792789113019,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDCR","award":["R01DE029468"],"award-info":[{"award-number":["R01DE029468"]}]},{"name":"NIH\/NIDCR","award":["RO1AG087335"],"award-info":[{"award-number":["RO1AG087335"]}]},{"name":"NIH\/NIA","award":["R01DE029468"],"award-info":[{"award-number":["R01DE029468"]}]},{"name":"NIH\/NIA","award":["RO1AG087335"],"award-info":[{"award-number":["RO1AG087335"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The occurrence and severity of periodontitis (PD) tend to increase with age, and yet the underlying mechanisms remain unclear. Immune senescence is known to be triggered in mice and humans as they age. Experimental PD in mice has been shown to induce senescence biomarkers p16 INK4a and p21, dysfunction of antigen-presenting cells (APCs), and activation of the senescence-associated secretory phenotype (SASP). However, the causal links of senescence to experimental PD are not yet established. This study aims to elucidate the role of senescence in experimental PD at a causal level. The P16-3MR mouse model harbors the p16INK4a (Cdkn2a) promoter, driving in vivo expression of synthetic Renilla luciferase, monomeric red fluorescent protein (mRFP), and herpes simplex virus-1 thymidine kinase (HSV-TK). This facilitates in vivo identification of p16 INK4a activation at the cellular level and the consequences of selective elimination of p16INK4a-positive cells by ganciclovir (GCV) treatment. Mice were treated with\/without GCV for two weeks during ligature-induced PD. In vivo bioluminescence imaging quantified p16INK4a activation, while Western blot and immunofluorescence analyses assessed key senescence and inflammatory markers (p16, p21, p53, Cyclin D1, p-H2A.X, IL17, and IL1\u03b2). Alveolar bone volume was analyzed by micro-CT and histomorphometry. Our findings demonstrate that clearance of senescent cells in mice subjected to experimental PD alleviates inflammation and mitigates bone loss. These results suggest a causal role for senescence in PD pathology, raising the future prospect of senolytic agents for therapeutic intervention in PD.<\/jats:p>","DOI":"10.3390\/cells14030226","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T05:50:36Z","timestamp":1738734636000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Role of Senescence in Experimental Periodontitis at the Causal Level: An in Vivo Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8020-9750","authenticated-orcid":false,"given":"Xiaogang","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Elashiry","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-6206","authenticated-orcid":false,"given":"Celine Joyce","family":"Cornelius Timothius","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5034-4109","authenticated-orcid":false,"given":"Ranya","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Periodontics, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/00220345211037977","article-title":"Periodontitis and accelerated biological aging: A geroscience approach","volume":"101","author":"Baima","year":"2022","journal-title":"J. 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