Journal Article

Causal effects of denture wearing on epigenetic age acceleration and the mediating pathways: a mendelian randomization study

Cheng, Zheng, Xu, Junyu, Zhao, Zhibai, Chen, Xin, Wang, Qianyi, Jiang, Qianglin

2024

Overview

Background 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. Methods 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. Results 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). Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Aging / Aging - genetics / Bleeding / Body fat / Body mass index / Cardiovascular disease / Complications and side effects / Dental caries / Dental research / Dentistry / Dentures / Dentures - adverse effects / DNA methylation / Epigenesis, Genetic / Epigenetic age acceleration / Epigenetic inheritance / Epigenetics / Genetic aspects / Genome-wide association studies / Genome-Wide Association Study / Gingiva / Gum disease / Health aspects / Humans / Mediation analysis / Mediators / Medicine / Mendelian Randomization Analysis / Mouth diseases / Obesity / Observational studies / Oral and Maxillofacial Surgery / Oral health / Oral hygiene / Oxidative stress / Periodontitis / Pleiotropy / Risk factors / Sensitivity analysis / Teeth / Tumor necrosis factor-TNF / Ulcers