Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA.
Aging (Albany NY). 2024 Feb 26;16(4):3107-3136. doi: 10.18632/aging.205602.
Epigenetic gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.
出生时的表观遗传孕龄加速（EGAA）和儿童时期的表观遗传年龄加速（EAA）可能是宫内环境的生物标志物。我们研究了孕妇血液中叶酸、B 族维生素、5 种必需和 7 种非必需金属在第一孕期的含量与生命早期 EGAA 和 EAA 的相关性。使用 Bohlin EGAA 和 Horvath 多组织和皮肤及血液 EAA 计算方法，计算了脐带血（N=351）和儿童中期血液（N=326；中位年龄=7.7 岁）中 DNA 甲基化的结果，这些结果来自产前项目 Viva 预出生队列。个体必需金属（铜、锰和锌）的一个标准差增加与出生时 Horvath EAA 降低 0.94-1.2 周有关，探索性因子分析确定的暴露模式表明，必需金属的共同来源与 Horvath EAA 有关。我们还观察到锌与 Bohlin EGAA、镁和铅与 Horvath EAA 以及铯与出生时皮肤和血液 EAA 之间存在非线性关联的证据。总的来说，出生时的关联在儿童中期并没有持续存在；然而，砷与出生时和儿童时期更大的 EAA 有关。产前金属，包括必需金属和砷，与生命早期的表观遗传衰老有关，这可能与未来的健康有关。
