Most of the elderly population is afflicted by periodontal diseases, creating a health burden worldwide. Cellular senescence is one of the hallmarks of aging and associated with several chronic comorbidities. Senescent cells produce a variety of deleterious secretions, collectively termed the senescence-associated secretory phenotype (SASP). This disrupts neighboring cells, leading to further senescence propagation and inciting chronic inflammation, known as "inflammaging." Detrimental repercussions within the tissue microenvironment can trigger senescence at a younger age, accelerate biological aging, and drive the initiation or progression of diseases. Here, we investigated the biological signatures of senescence in healthy and diseased gingival tissues by assessing the levels of key senescence markers (p16, lipofuscin, and β-galactosidase) and inflammatory mediators (interleukin [IL]-1β, IL-6, IL-8, matrix metalloproteinase [MMP]-1, MMP-3, and tumor necrosis factor-α). Our results showed significantly increased senescence features including p16, lipofuscin, and β-galactosidase in both epithelial and connective tissues of periodontitis patients compared with healthy sites in all age groups, indicating that an inflammatory microenvironment can trigger senescence-like alterations in younger diseased gingival tissues as well. Subsequent analyses using double staining with specific cell markers noted the enrichment of β-galactosidase in fibroblasts and macrophages. Concurrently, inflammatory mediators consistent with SASP were increased in the gingival biopsies obtained from periodontitis lesions. Together, our findings provide the first clinical report revealing susceptibility to elevated senescence and inflammatory milieu consistent with senescence secretome in gingival tissues, thus introducing senescence as one of the drivers of pathological events in the oral mucosa and a novel strategy for targeted interventions.

中文翻译：

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牙周炎衰老的分子特征：临床见解。


大多数老年人都患有牙周病，给全世界带来了健康负担。细胞衰老是衰老的标志之一，并与多种慢性合并症相关。衰老细胞产生多种有害分泌物，统称为衰老相关分泌表型（SASP）。这会破坏邻近的细胞，导致进一步衰老传播并引发慢性炎症，称为“炎症”。组织微环境内的有害影响可能会在年轻时引发衰老，加速生物衰老，并推动疾病的发生或进展。在这里，我们通过评估关键衰老标志物（p16、脂褐质和 β-半乳糖苷酶）和炎症介质（白细胞介素 [IL]-1β、IL-6、IL-6）的水平，研究了健康和患病牙龈组织衰老的生物学特征。 8、基质金属蛋白酶[MMP]-1、MMP-3和肿瘤坏死因子-α）。我们的结果显示，与所有年龄段的健康部位相比，牙周炎患者的上皮和结缔组织中的衰老特征（包括 p16、脂褐素和 β-半乳糖苷酶）显着增加，表明炎症微环境可以引发年轻患病牙龈组织的衰老样改变以及。随后使用特定细胞标记物双染色进行的分析表明，成纤维细胞和巨噬细胞中β-半乳糖苷酶富集。同时，从牙周炎病变获得的牙龈活检中，与 SASP 一致的炎症介质增加。 总之，我们的研究结果提供了第一份临床报告，揭示了衰老和炎症环境的易感性升高，与牙龈组织中的衰老分泌组一致，从而将衰老作为口腔粘膜病理事件的驱动因素之一，并提供了一种有针对性的干预新策略。