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新型非人类灵长类动物模型中衰老过程中的口腔健康变化。

Changes in oral health during aging in a novel non-human primate model.

机构信息

Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Department of Periodontics, Department of Cell Systems and Anatomy, Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

出版信息

Geroscience. 2024 Apr;46(2):1909-1926. doi: 10.1007/s11357-023-00939-7. Epub 2023 Sep 29.

Abstract

Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well understood due to challenges with current animal models. In this study, we analyzed the oral health and microbiota of a short-lived non-human primate (i.e., marmoset), as a step towards establishing a surrogate for studying the changes that occur in oral health during human aging. We investigated the oral health of marmosets using cadaveric tissues in three different cohorts: young (aged ≤6 years), middle-aged, and older (>10 years) and assessed the gingival bacterial community using analyses of the V3-V4 variable region of 16S rRNA gene. The oldest cohort had a significantly higher number of dental caries, increased dental attrition/erosion, and deeper periodontal pocket depth scores. Oral microbiome analyses showed that older marmosets had a significantly greater abundance of Escherichia-Shigella and Propionibacterium, and a lower abundance of Agrobacterium/Rhizobium at the genus level. Alpha diversity of the microbiome between the three groups showed no significant differences; however, principal coordinate analysis and non-metric multidimensional scaling analysis revealed that samples from middle-aged and older marmosets were more closely clustered than the youngest cohort. In addition, linear discriminant analysis effect size (LEFSe) identified a higher abundance of Esherichia-Shigella as a potential pathogenic biomarker in older animals. Our findings confirm that changes in the oral microbiome are associated with a decline in oral health in aging marmosets. The current study suggests that the marmoset model recapitulates some of the changes in oral health associated with human aging and may provide opportunities for developing new preventive strategies or interventions which target these disease conditions.

摘要

口腔健康对老年人群的生活质量和整体健康状况起着重要作用。然而,由于当前动物模型存在挑战,人们对与年龄相关的口腔健康变化了解甚少。在这项研究中,我们分析了短寿命非人类灵长类动物(即狨猴)的口腔健康和微生物群,以期建立一种替代模型来研究人类衰老过程中口腔健康的变化。我们使用三个不同队列的尸体组织研究了狨猴的口腔健康:年轻(≤6 岁)、中年和老年(>10 岁),并使用 16S rRNA 基因 V3-V4 可变区分析评估了牙龈细菌群落。最年长的队列的龋齿数量明显更高,牙齿磨损/侵蚀增加,牙周袋深度评分更深。口腔微生物组分析表明,老年狨猴属埃希氏菌-志贺氏菌和丙酸杆菌的丰度显著增加,而农杆菌/根瘤菌的丰度则显著降低。三组间微生物组的 alpha 多样性没有显著差异;然而,主坐标分析和非度量多维尺度分析表明,中年和老年狨猴的样本比最年轻的队列更紧密地聚集。此外,线性判别分析效应量(LEFSe)鉴定出埃希氏菌-志贺氏菌的丰度较高,是老年动物中一种潜在的致病生物标志物。我们的研究结果证实,口腔微生物组的变化与衰老狨猴口腔健康状况的下降有关。本研究表明,狨猴模型再现了与人类衰老相关的一些口腔健康变化,可能为开发针对这些疾病状况的新预防策略或干预措施提供机会。

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