The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

认知表现、宏观和微观结构的大脑解剖结构与加速衰老之间的关系尚未得到研究，这种关系由一种高度准确的衰老表观遗传生物标志物（称为健康青少年的表观遗传时钟）衡量。对参加开普敦青少年抗逆转录病毒队列研究的健康青少年进行了横断面研究。Illumina Infinium 甲基化 EPIC 阵列用于从 44 名 9 至 12 岁青少年的血液样本中生成 DNA 甲基化数据。表观遗传时钟软件和方法用于估计两种测量值，即表观遗传年龄加速残差（AAR）和外在表观遗传年龄加速（EEAA）。每个参与者都接受了神经认知测试、T1 结构磁共振成像 (MRI) 和弥散张量成像 (DTI)。在两个表观遗传老化措施和 10 个认知功能域之间进行相关测试，以评估随着表观遗传老化增加认知表现的差异。为了研究表观遗传年龄加速对大脑结构的关联，我们在 R（版本 3.4.3，2017）中开发了逐步多元回归模型，包括灰质和白质体积、皮质厚度和皮质表面积，以及 DTI 测量白质微观结构完整性。除了对两个认知领域产生负面影响外，视觉记忆（我们在 R（版本 3.4.3，2017）中开发了逐步多元回归模型，包括灰质和白质体积、皮质厚度和皮质表面积，以及白质微结构完整性的 DTI 测量。除了对两个认知领域产生负面影响外，视觉记忆（我们在 R（版本 3.4.3，2017）中开发了逐步多元回归模型，包括灰质和白质体积、皮质厚度和皮质表面积，以及白质微结构完整性的 DTI 测量。除了对两个认知领域产生负面影响外，视觉记忆（p  = .026) 和视觉空间敏锐度 ( p  = .02)，表观遗传年龄加速与脑容量、皮质厚度、皮质表面积的改变以及一系列区域神经元微结构的异常有关。压力是 AAR的重要预测因子 ( p = .029)。了解青少年表观遗传年龄加速的驱动因素可能会导致对青少年神经认知障碍发展的宝贵见解。