Alveolar bone loss is generally considered as a chronological age-related disease. As biological ageing process is not absolutely determined by increasing age, whether alveolar bone loss associated with increasing chronological age or biological ageing remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological ageing-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body ageing. 3635 participants from 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 two-sample Mendelian randomization study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4,376 individuals versus 361,194 individuals). As biological ageing related indicator, α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with down-regulated expression level of α-Klotho in 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 (OR=0.999, P=0.005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which especially stable in men (the optimal cut-off values were both 62 years old). For male above 62 years old, increasing age converted to protective factor and accompanied by alleviated alveolar bone loss. Alveolar bone loss which directly associated to decreased renal function and α-Klotho level was related to biological ageing rather than chronological age. The renal-alveolar bone axis could provide new sight of clinical therapy in alveolar bone loss.

中文翻译：

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解读生物衰老对牙槽骨丢失的影响：α-Klotho 和肾功能动力学的见解


牙槽骨丢失通常被认为是一种与年龄相关的疾病。由于生物衰老过程并不绝对由年龄增加决定，牙槽骨丢失是否与实际年龄增加有关或与生物衰老有关尚不清楚。准确区分牙槽骨丢失是与时间年龄相关还是与生物衰老相关对于选择适当的临床治疗方法至关重要。本研究旨在确定牙槽骨流失与身体衰老之间的关系。纳入了来自国家健康和营养检查调查的 3635 名参与者以及来自基因表达综合数据集的 71 名活体肾移植受者。采用多元回归分析、平滑曲线拟合和广义相加模型探讨牙槽骨丢失、年龄、血清α-Klotho水平、肾功能标志物以及术前肌酐和肾皮质相关α-Klotho基因表达水平之间的关联。同时，进行了一项双样本孟德尔随机化研究，以评估 α-Klotho 与牙周病之间的因果关系（4,376 名个体与 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，牙槽骨丢失加剧。 MR 分析使用 IVW 进一步确定了基因预测的较高 α-Klotho 浓度与牙槽骨丢失易感性之间的负相关性（OR=0.999，P=0.005）。 然而，我们观察到实际年龄和牙槽骨丢失之间呈倒 U 形关联，这种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，并伴随着牙槽骨丢失的减轻。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视角。