Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Geroscience. 2022 Dec;44(6):2671-2684. doi: 10.1007/s11357-022-00626-z. Epub 2022 Aug 10.
DNA methylation (DNAm) patterns across the genome changes during aging and development of complex diseases including type 2 diabetes (T2D). Our study aimed to estimate DNAm trajectories of CpG sites associated with T2D, epigenetic age (DNAmAge), and age acceleration based on four epigenetic clocks (GrimAge, Hannum, Horvath, phenoAge) in the period 10 years prior to and up to T2D onset. In this nested case-control study within Doetinchem Cohort Study, we included 132 incident T2D cases and 132 age- and sex-matched controls. DNAm was measured in blood using the Illumina Infinium Methylation EPIC array. From 107 CpG sites associated with T2D, 10 CpG sites (9%) showed different slopes of DNAm trajectories over time (p < 0.05) and an additional 8 CpG sites (8%) showed significant differences in DNAm levels (at least 1%, p-value per time point < 0.05) at all three time points with nearly parallel trajectories between incident T2D cases and controls. In controls, age acceleration levels were negative (slower epigenetic aging), while in incident T2D cases, levels were positive, suggesting accelerated aging in the case group. We showed that DNAm levels at specific CpG sites, up to 10 years before T2D onset, are different between incident T2D cases and healthy controls and distinct patterns of clinical traits over time may have an impact on those DNAm profiles. Up to 10 years before T2D diagnosis, cases manifested accelerated epigenetic aging. Markers of biological aging including age acceleration estimates based on Horvath need further investigation to assess their utility for predicting age-related diseases including T2D.
基因组中的 DNA 甲基化 (DNAm) 模式会随着年龄的增长和包括 2 型糖尿病 (T2D) 在内的复杂疾病的发展而发生变化。我们的研究旨在估计与 T2D 相关的 CpG 位点的 DNAm 轨迹、表观遗传年龄 (DNAmAge) 和基于四个表观遗传时钟 (GrimAge、Hannum、Horvath、phenoAge) 的年龄加速，时间范围为 T2D 发病前 10 年至发病时。在 Doetinchem 队列研究的嵌套病例对照研究中，我们纳入了 132 例新发 T2D 病例和 132 例年龄和性别匹配的对照。使用 Illumina Infinium Methylation EPIC 阵列测量血液中的 DNAm。在与 T2D 相关的 107 个 CpG 位点中，有 10 个 CpG 位点 (9%) 的 DNAm 轨迹随时间变化的斜率不同 (p < 0.05)，另外 8 个 CpG 位点 (8%) 的 DNAm 水平差异显著 (至少 1%，每个时间点的 p 值 < 0.05)，在所有三个时间点，新发 T2D 病例和对照之间的轨迹几乎平行。在对照中，年龄加速水平为负 (表观遗传衰老较慢)，而在新发 T2D 病例中，水平为正，表明病例组衰老加速。我们表明，在 T2D 发病前长达 10 年，与新发 T2D 病例和健康对照相比，特定 CpG 位点的 DNAm 水平不同，并且随着时间的推移，临床特征的不同模式可能对这些 DNAm 谱产生影响。在 T2D 诊断前长达 10 年，病例表现出加速的表观遗传衰老。基于 Horvath 的生物衰老标志物包括年龄加速估计值需要进一步研究，以评估其在预测包括 T2D 在内的与年龄相关的疾病中的效用。
