Mi Panpan, Cao Xu, Feng Haixia, Wang Huijie
Department of Orthopedic, Hebei PetroChina Central Hospital, Langfang, China.
Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China.
Front Public Health. 2025 Apr 15;13:1504830. doi: 10.3389/fpubh.2025.1504830. eCollection 2025.
DNA methylation (DNAm) is a sensitive biomarker of aging-related processes, and novel epigenetic-based "clocks" can estimate accelerated biological aging. Cadmium (Cd) can alter cellular processes that promote aging and disrupt global methylation patterns. However, few studies have investigated the association between blood Cd and accelerated aging. We aimed to investigate the association between blood Cd and four DNAm-based epigenetic age accelerations in individuals over 50 in the United States, using data from the National Health and Nutrition Examination Survey (NHANES).
DNAm-epigenetic biomarkers and blood Cd data from the NHANES database (1999-2002) were retrieved for this study. We evaluated four epigenetic ages: HorvathAge, HannumAge, PhenoAge, and GrimAge. Age acceleration was calculated by extracting the residuals from the regression of chronological age on each epigenetic age measure. We used weighted linear regression models and subgroup analyses to investigate the associations between blood Cd levels and these age accelerations, adjusting for potential confounding factors.
Higher blood Cd levels (≥0.5 μg/dl) were significantly associated with increased age acceleration for PhenoAge (β = 1.37, = 0.017) and GrimAge (β = 1.31, = 0.003) in adjusted models. A significant association was also observed for HannumAge (β = 0.94, = 0.016), although this association was not significant for continuous Cd levels ( = 0.111). No significant associations were found for HorvathAge. Subgroup analyses indicated consistent associations across demographic and lifestyle subgroups, with no significant interactions.
In this study, after adjusting for confounders, blood Cd levels were positively associated with PhenoAge acceleration and GrimAge acceleration in people over 50 in the United States. These results may be useful in proposing interventions in environmental exposures to slow the aging process and prevent age-related diseases.
DNA甲基化（DNAm）是衰老相关过程的敏感生物标志物，新型基于表观遗传学的“时钟”可以估计加速的生物衰老。镉（Cd）可改变促进衰老的细胞过程并扰乱整体甲基化模式。然而，很少有研究调查血镉与加速衰老之间的关联。我们旨在利用美国国家健康与营养检查调查（NHANES）的数据，调查美国50岁以上人群血镉与四种基于DNAm的表观遗传年龄加速之间的关联。
本研究检索了NHANES数据库（1999 - 2002年）中的DNAm表观遗传生物标志物和血镉数据。我们评估了四个表观遗传年龄：HorvathAge、HannumAge、PhenoAge和GrimAge。通过从每个表观遗传年龄测量值的实际年龄回归中提取残差来计算年龄加速。我们使用加权线性回归模型和亚组分析来研究血镉水平与这些年龄加速之间的关联，并对潜在的混杂因素进行调整。
在调整模型中，较高的血镉水平（≥0.5μg/dl）与PhenoAge（β = 1.37，P = 0.017）和GrimAge（β = 1.31，P = 0.003）的年龄加速增加显著相关。HannumAge也观察到显著关联（β = 0.94，P = 0.016），尽管这种关联在连续镉水平下不显著（P = 0.111）。未发现HorvathAge有显著关联。亚组分析表明，在人口统计学和生活方式亚组中存在一致的关联，无显著交互作用。
在本研究中，调整混杂因素后，美国50岁以上人群的血镉水平与PhenoAge加速和GrimAge加速呈正相关。这些结果可能有助于提出针对环境暴露的干预措施，以减缓衰老过程并预防与年龄相关的疾病。
