Abstract：
Alveolar bone loss is generally considered a chronological age-related disease. As biological aging process is not absolutely determined by increasing age, whether alveolar bone loss is associated with increasing chronological age or biological aging remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological aging-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body aging. In total, 3 635 participants from the National Health and Nutrition Examination Survey and 71 living kidney transplant recipients from Gene Expression Omnibus Datasets were enrolled. Multivariate regression analysis, smooth curve fittings, and generalized additive models were used to explore the association among alveolar bone loss, age, serum α-Klotho level, renal function markers, as well as between preoperative creatinine and renal cortex-related α-Klotho gene expression level. Meanwhile, a 2-sample Mendelian randomization (MR) study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4 376 individuals vs 361 194 individuals). As a biological aging-related indicator, the α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with a downregulated expression level of α-Klotho in the renal cortex and aggravated alveolar bone loss. The MR analysis further identified the negative association between higher genetically predicted α-Klotho concentrations with alveolar bone loss susceptibility using the IVW (odds ratio [OR] = 0.999, p = .005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which is especially stable in men (the optimal cutoff values were both 62 years old). For men above 62 years old, increasing age is converted to protective factor and is accompanied by alleviated alveolar bone loss. Alveolar bone loss that is directly associated with decreased renal function and α-Klotho level was related to biological aging rather than chronological age. The renal-alveolar bone axis could provide a new sight of clinical therapy in alveolar bone loss.
摘要：
牙槽骨丢失通常被认为是与年龄相关的疾病。由于生物衰老过程并非绝对由年龄增长决定，牙槽骨丢失是否与年龄增长或生物老化相关尚不清楚.准确区分牙槽骨丢失是与年龄相关的还是与生物老化相关的，对于选择合适的临床治疗方法至关重要。本研究旨在确定牙槽骨丢失与身体老化之间的关系。纳入来自全国健康和营养检查调查的3635名参与者和来自基因表达综合数据集的71名活体肾移植受者。多元回归分析，平滑曲线拟合和广义加性模型用于探索牙槽骨丢失之间的关联，年龄,血清α-Klotho水平，肾功能标志物，术前肌酐与肾皮质相关的α-Klotho基因表达水平。同时,我们进行了一项孟德尔随机双样本研究,以评估α-Klotho与牙周病之间的因果关系(4,376名个体对361,194名个体).作为生物衰老相关指标，α-Klotho水平与肾功能受损和牙槽骨丢失呈负相关。相应地,伴随着肾功能下降，表现为肾皮质α-Klotho表达水平下调，牙槽骨丢失加重。使用IVW，MR分析进一步确定了较高的遗传预测α-Klotho浓度与牙槽骨丢失易感性之间的负相关（OR=0.999，P=0.005）。然而,在实际年龄和牙槽骨丢失之间观察到了一个倒U形关联，在男性中尤其稳定（最佳临界值均为62岁）。对于62岁以上的男性，年龄的增长转化为保护因素，并伴有减轻牙槽骨丢失。与肾功能和α-Klotho水平下降直接相关的牙槽骨丢失与生物衰老有关，而不是与实际年龄有关。肾-牙槽骨轴可为牙槽骨丢失的临床治疗提供新的思路。
