Considering that DNA methylation (DNAm) profiles are, in large part, modifiable by lifestyle and environmental influences, it has been proposed that epigenetic clocks provide a better estimate of biological age than chronological age, as associated with current health status. Even though metabolic diseases induce precocious aging, little is known about associations between metabolic syndrome (MetS) and DNA methylation clocks, and stochastic epigenetic mutations (SEMs), in a Korean population. Therefore, we assessed four different epigenetic clocks (Pan-tissue, Hannum, PhenoAge, and GrimAge), and their accelerations, on MetS and MetS-related lifestyle factors, in Koreans. We measured genome-wide DNA methylation (485,512 CpGs), using an Illumina 450 methylation BeadChip array, with data from 349 blood samples. DNAm GrimAge strongly correlated with chronological age (r = 0.77, p < 0.001) compared to the other three epigenetic clocks and SEMs. DNAm-based surrogate markers, with regard to MetS, including the gene encoding plasminogen activator inhibitor-1 (PAI1), also correlated with chronological age. Within cohorts stratified by age group, sex, regional area, smoking, and alcohol drinking, a positive correlation was observed between DNAm GrimAge and chronological age (0.43 ≤ r ≤ 0.78). In particular, we identified MetS to associate with accelerated GrimAge, and age-adjusted PAI1, in the middle-age group. Accerelated GrimAge also associated with risk of MetS in the middle-age group (odds ratio = 1.16, p = 0.046), which appears to mediate their associations with fasting glucose. Multiple linear regression showed that DNAm GrimAge, and its acceleration, associate with MetS scores, in the middle-age group (r = 0.26, p = 0.006). Age-adjusted PAI1 was also significantly different between the MetS and control groups, and further associated with MetS scores (r = 0.31, P < 0.001), in the middle age group. DNAm GrimAge is a surrogate marker for MetS, and its component score, in Koreans. This association can be observed only in middle age. Therefore, appropriate DNA methylation clocks may aid in the prediction of Korean metabolic diseases.

中文翻译：

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DNA甲基化和表观遗传时钟对韩国中年人代谢疾病的影响

考虑到 DNA 甲基化 (DNAm) 谱在很大程度上可受生活方式和环境影响的影响，有人提出表观遗传时钟比实际年龄提供更好的生物学年龄估计，与当前健康状况相关。尽管代谢疾病会导致早熟，但对韩国人群中代谢综合征 (MetS) 与 DNA 甲基化时钟以及随机表观遗传突变 (SEM) 之间的关联知之甚少。因此，我们在韩国人中评估了四种不同的表观遗传时钟（Pan-tissue、Hannum、PhenoAge 和 GrimAge）及其对 MetS 和 MetS 相关生活方式因素的加速。我们使用 Illumina 450 甲基化 BeadChip 阵列测量了全基因组 DNA 甲基化（485,512 个 CpG），数据来自 349 个血液样本。与其他三个表观遗传时钟和 SEM 相比，DNAm GrimAge 与实足年龄密切相关（r = 0.77，p < 0.001）。基于 DNAm 的替代标记，关于 MetS，包括编码纤溶酶原激活物抑制剂-1 (PAI1) 的基因，也与实足年龄相关。在按年龄组、性别、区域、吸烟和饮酒分层的队列中，观察到 DNAm GrimAge 与实足年龄呈正相关（0.43 ≤ r ≤ 0.78）。特别是，我们发现 MetS 与中年组的加速 GrimAge 和年龄调整的 PAI1 相关联。加速相关的 GrimAge 还与中年组的 MetS 风险相关（比值比 = 1.16，p = 0.046），这似乎介导了它们与空腹血糖的关联。多元线性回归表明 DNAm GrimAge 及其加速度，与中年组的 MetS 分数相关联（r = 0.26，p = 0.006）。年龄调整后的 PAI1 在 MetS 组和对照组之间也存在显着差异，并进一步与中年组的 MetS 评分相关（r = 0.31，P < 0.001）。DNAm GrimAge 是韩国人的 MetS 及其组成分数的替代标记。这种关联只能在中年时观察到。因此，适当的 DNA 甲基化时钟可能有助于预测韩国代谢疾病。这种关联只能在中年观察到。因此，适当的 DNA 甲基化时钟可能有助于预测韩国代谢疾病。这种关联只能在中年观察到。因此，适当的 DNA 甲基化时钟可能有助于预测韩国代谢疾病。