Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.

中文翻译：

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单核转录组学揭示了 YAP 在灵长类牙龈衰老中的衰老保护作用。


衰老对牙龈产生深远的影响，并显着增加其对牙周炎（一种世界范围内流行的炎症性疾病）的易感性。然而，对于牙龈老化的调控机制仍缺乏系统的表征和全面的理解。在这里，我们系统地剖析了灵长类动物衰老过程中牙龈的表型特征，并构建了第一个牙龈衰老的单核转录组图景，通过该图谱阐明了一组细胞类型特异性特征。上皮细胞被认为是牙龈中老化受影响最大的细胞类型。进一步的分析指出了 YAP 在上皮细胞自我更新和稳态中的关键作用，在上皮细胞（尤其是基底细胞）衰老过程中，YAP 会下降。在人类牙龈组织中证实了衰老过程中 YAP 活性的下降，人原代牙龈角质形成细胞中 YAP 的下调再现了在衰老灵长类牙龈中观察到的主要表型缺陷，而 YAP 的过度表达则显示出年轻化效果。我们的工作提供了对牙龈衰老的深入了解，并为开发对抗衰老相关牙龈疾病的新策略提供了丰富的资源，最终目标是促进牙周健康和促进健康老龄化。