加速的表观遗传衰老与多种心血管代谢、血液学和肾脏异常相关：一项项目基线健康子研究。
Accelerated Epigenetic Aging Is Associated With Multiple Cardiometabolic, Hematologic, and Renal Abnormalities: A Project Baseline Health Substudy.
机构信息
Duke University Medical Center (B.U.), Duke University.
Duke Molecular Physiology Institute (L.C.K., S.H.S.), Duke University.
出版信息
Circ Genom Precis Med. 2023 Jun;16(3):216-223. doi: 10.1161/CIRCGEN.122.003772. Epub 2023 Apr 11.
BACKGROUND
Epigenetic clocks estimate chronologic age using methylation levels at specific loci. We tested the hypothesis that accelerated epigenetic aging is associated with abnormal values in a range of clinical, imaging, and laboratory characteristics.
METHODS
The Project Baseline Health Study recruited 2502 participants, including 1661 with epigenetic age estimates from the Horvath pan-tissue clock. We classified individuals with extreme values as having epigenetic age acceleration (EAA) or epigenetic age deceleration. A subset of participants with longitudinal methylation profiling was categorized as accelerated versus nonaccelerated. Using principal components analysis, we created phenoclusters using 122 phenotypic variables and compared individuals with EAA versus epigenetic age deceleration, and at one year of follow-up, using logistic regression models adjusted for sex (false discovery rate [] <0.10); in secondary exploratory analyses, we tested individual clinical variables.
RESULTS
The EAA (n=188) and epigenetic age deceleration (n=195) groups were identified as having EAA estimates ≥5 years or ≤-5 years, respectively. In primary analyses, individuals with EAA had higher values for phenoclusters summarizing lung function and lipids, and lower values for a phenocluster representing physical function. In secondary analyses of individual variables, neutrophils, body mass index, and waist circumference were significantly higher in individuals with EAA (<0.10). No phenoclusters were significantly different between participants with accelerated (n=148) versus nonaccelerated (n=112) longitudinal aging.
CONCLUSIONS
We report multiple cardiometabolic, hematologic, and physical function features characterizing individuals with EAA. These highlight factors that may mediate the adverse effects of aging and identify potential targets for study of mitigation of these effects.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03154346.
背景
表观遗传时钟使用特定基因座的甲基化水平来估计年龄。我们检验了这样一种假设，即加速的表观遗传衰老与一系列临床、影像学和实验室特征的异常值有关。
方法
基础健康研究项目招募了 2502 名参与者，其中 1661 名参与者的表观遗传年龄估计值来自霍瓦特多组织时钟。我们将极端值个体归类为具有表观遗传年龄加速（EAA）或表观遗传年龄减速。亚组参与者进行了纵向甲基化分析，分类为加速与非加速。使用主成分分析，我们使用 122 个表型变量创建表型聚类，并使用逻辑回归模型比较 EAA 与表观遗传年龄减速个体，以及在一年随访时，调整性别（错误发现率[]<0.10）；在二级探索性分析中，我们测试了个别临床变量。
结果
EAA（n=188）和表观遗传年龄减速（n=195）组分别被确定为表观遗传年龄估计值≥5 年或≤-5 年。在主要分析中，EAA 个体的肺功能和脂质表型聚类值较高，而身体功能表型聚类值较低。在对个别变量的二级分析中，EAA 个体的中性粒细胞、体重指数和腰围显著较高（<0.10）。在加速（n=148）与非加速（n=112）纵向老化的参与者之间，没有表型聚类存在显著差异。
结论
我们报告了多种代谢、血液和身体功能特征，这些特征描述了 EAA 个体。这些特征突出了可能介导衰老不良影响的因素，并确定了研究减轻这些影响的潜在目标。
注册
网址：https://www.
临床试验
gov；独特标识符：NCT03154346。
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