This study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation.
We recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations.
Plasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE.
Plasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.
目的:本研究旨在探讨ETEs与4种表观遗传衰老指标的相关性,并评估炎症的潜在介导作用。
方法:我们在2018年10月至2019年8月期间从医院招募了93名个人。钴的血浆水平,铜,铁,锰,钼,硒,通过ICP-MS测量锌,使用Illumina甲基化EPIC珠芯片测量白细胞DNA甲基化水平。使用线性回归来估计七个血浆ETEs与表观遗传衰老指标之间的关联。使用加权分位数和(WQS)回归和贝叶斯核机回归(BKMR)模型来评估ETE混合物的效果。使用四个全身炎症指标评估炎症状态(中性粒细胞与淋巴细胞比率(NLR),血小板与淋巴细胞比率(PLR),单核细胞与淋巴细胞比率(MLR),和全身免疫炎症指数(SII))和三种细胞因子(IL-4,IL-6和IL-13)。进行中介分析以探讨炎症在上述关联中的作用。
结果:血浆硒水平与DunedinPACE呈显著负相关,而Cu水平与之呈显著正相关。WQS回归和BKMR模型均表明,Se和Cu主导了ETEs混合物的作用。MLR和白细胞介素6与DunedinPACE呈显著正相关。进一步的介导分析表明,炎症部分介导了ETEs和DunedinPACE之间的关联。
结论:血浆Se和Cu水平与表观遗传衰老密切相关,炎症可能是这种关系的潜在机制。这些发现有助于预防与人口老龄化相关的健康危害。