Department of Oral and Maxillofacial Surgery, Jiangyin People's Hospital Affiliated to Nantong University, No.163, Shoushan Road, Jiangyin, 214400, Jiangsu Province, China.
Department of Cardiology, Jiangyin People's Hospital Affiliated to Nantong University, No.163, Shoushan Road, Jiangyin, 214400, Jiangsu Province, China.
BMC Oral Health. 2024 Jul 13;24(1):788. doi: 10.1186/s12903-024-04578-y.
The epigenetic-age acceleration (EAA) represents the difference between chronological age and epigenetic age, reflecting accelerated biological aging. Observational studies suggested that oral disorders may impact DNA methylation patterns and aging, but their causal relationship remains largely unexplored. This study aimed to investigate potential causal associations between dental traits and EAA, as well as to identify possible mediators.
Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate the overall and independent effects of ten dental traits (dentures, bleeding gums, painful gums, loose teeth, toothache, ulcers, periodontitis, number of teeth, and two measures of caries) on four EAA subtypes (GrimAge acceleration [GrimAA], PhenoAge acceleration [PhenoAA], HannumAge acceleration [HannumAA] and intrinsic EAA [IEAA]), and used two-step Mendelian randomization to evaluate twelve potential mediators of the associations. Comprehensive sensitivity analyses were used to verity the robustness, heterogeneity, and pleiotropy.
Univariable inverse variance weighted MR analyses revealed a causal effect of dentures on greater GrimAA (β: 2.47, 95% CI: 0.93-4.01, p = 0.002), PhenoAA (β: 3.00, 95% CI: 1.15-4.85, p = 0.001), and HannumAA (β: 1.96, 95% CI: 0.58-3.33, p = 0.005). In multivariable MR, the associations remained significant after adjusting for periodontitis, caries, number of teeth and bleeding gums. Three out of 12 aging risk factors were identified as mediators of the association between dentures and EAA, including body mass index, body fat percentage, and waist circumference. No evidence for reverse causality and pleiotropy were detected (p > 0.05).
Our findings supported the causal effects of genetic liability for denture wearing on epigenetic aging, with partial mediation by obesity. More attention should be paid to the obesity-monitoring and management for slowing EAA among denture wearers.
表观遗传年龄加速（EAA）代表了实际年龄和表观遗传年龄之间的差异，反映了生物衰老的加速。观察性研究表明，口腔疾病可能会影响 DNA 甲基化模式和衰老，但它们之间的因果关系仍在很大程度上尚未得到探索。本研究旨在调查牙齿特征与 EAA 之间的潜在因果关系，并确定可能的中介因素。
使用主要为欧洲血统的全基因组关联研究的汇总统计数据，我们进行了单变量和多变量 Mendelian 随机化（MR），以估计十种牙齿特征（义齿、牙龈出血、牙龈疼痛、松动牙齿、牙痛、溃疡、牙周炎、牙齿数量和两种龋齿测量值）对四种 EAA 亚型（GrimAge 加速[GrimAA]、PhenoAge 加速[PhenoAA]、HannumAge 加速[HannumAA]和内在 EAA[IEAA]）的总体和独立影响，并使用两步 Mendelian 随机化来评估关联的十二个潜在中介因素。综合敏感性分析用于验证稳健性、异质性和多效性。
单变量逆方差加权 MR 分析显示，义齿与更大的 GrimAA（β：2.47，95%置信区间：0.93-4.01，p=0.002）、PhenoAA（β：3.00，95%置信区间：1.15-4.85，p=0.001）和 HannumAA（β：1.96，95%置信区间：0.58-3.33，p=0.005）之间存在因果关系。在多变量 MR 中，在调整了牙周炎、龋齿、牙齿数量和牙龈出血后，关联仍然显著。12 种衰老风险因素中有 3 种被确定为义齿与 EAA 之间关联的中介因素，包括体重指数、体脂肪百分比和腰围。未发现反向因果关系和多效性的证据（p>0.05）。
我们的研究结果支持戴假牙的遗传易感性对表观遗传衰老的因果影响，部分通过肥胖来介导。对于戴假牙者，应更加关注肥胖监测和管理，以减缓 EAA 的发生。
