Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Epidemiology and Biostatistics, University of California, San Francisco.
JAMA Netw Open. 2023 Jun 1;6(6):e2317987. doi: 10.1001/jamanetworkopen.2023.17987.
Adverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs.
To investigate the associations of ACEs with changes in epigenetic age acceleration (EAA), a biomarker associated with various health outcomes in middle-aged adults, in a population with balanced race and sex demographics.
DESIGN, SETTING, AND PARTICIPANTS: Data for this cohort study were from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants in CARDIA underwent 8 follow-up exams from baseline (year 0 [Y0]; 1985-1986) to Y30 (2015-2016), and participant blood DNA methylation information was obtained at Y15 (2000-2001) and Y20 (2005-2006). Individuals from Y15 and Y20 with available DNA methylation data and complete variables for ACEs and covariates were included. Data were analyzed from September 2021 to August 2022.
Participant ACEs (general negligence, emotional negligence, physical violence, physical negligence, household substance abuse, verbal and emotional abuse, and household dysfunction) were obtained at Y15.
The primary outcome consisted of results from 5 DNA methylation-based EAA measurements known to be associated with biological aging and long-term health: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE), measured at Y15 and Y20. Linear regression and generalized estimating equations were used to assess associations of the burden of ACEs (≥4 vs <4 ACEs) with EAA adjusting for demographics, health-related behaviors, and early life and adult socioeconomic status.
A total of 895 participants for Y15 (mean [SD] age, 40.4 [3.5] years; 450 males [50.3%] and 445 females [49.7%]; 319 Black [35.6%] and 576 White [64.4%]) and 867 participants for Y20 (mean [SD] age, 45.4 [3.5] years; 432 males [49.8%] and 435 females [50.2%]; 306 Black [35.3%] and 561 White [64.7%]) were included after excluding participants with missing data. There were 185 participants with (20.7%) vs 710 participants without (79.3%) 4 or more ACEs at Y15 and 179 participants with (20.6%) vs 688 participants without (79.4%) 4 or more ACEs at Y20. Having 4 or more ACEs was positively associated with EAA in years at Y15 (EEAA: β = 0.60 years; 95% CI, 0.18-1.02 years; PhenoAA: β = 0.62 years; 95% CI = 0.13-1.11 years; GrimAA: β = 0.71 years; 95% CI, 0.42-1.00 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) and Y20 (IEAA: β = 0.41 years; 95% CI, 0.05-0.77 years; EEAA: β = 1.05 years; 95% CI, 0.66-1.44 years; PhenoAA: β = 0.57 years; 95% CI, 0.08-1.05 years; GrimAA: β = 0.57 years; 95% CI, 0.28-0.87 years; DunedinPACE: β = 0.01; 95% CI, 0.01-0.02) after adjusting for demographics, health-related behaviors, and socioeconomic status.
In this cohort study, ACEs were associated with EAA among middle-aged adults after controlling for demographics, behavior, and socioeconomic status. These findings of the associations between early life experience and the biological aging process in midlife may contribute to health promotion in a life course perspective.
不良的童年经历（ACEs）与较差的健康风险相关，识别分子机制可能为 ACEs 人群的健康促进奠定基础。
在种族和性别比例均衡的人群中，研究 ACEs 与表观遗传年龄加速（EAA）变化的关联，EAA 是与中年成年人各种健康结果相关的生物标志物。
设计、地点和参与者：本队列研究的数据来自冠状动脉风险发展中的年轻人（CARDIA）研究。CARDIA 中的参与者进行了 8 次随访检查，从基线（第 0 年[Y0]；1985-1986 年）到 Y30（2015-2016 年），并在 Y15（2000-2001 年）和 Y20（2005-2006 年）获得参与者的血液 DNA 甲基化信息。纳入了在 Y15 和 Y20 有可用 DNA 甲基化数据和 ACEs 及协变量完整变量的个体。数据分析于 2021 年 9 月至 2022 年 8 月进行。
参与者的 ACEs（一般忽视、情感忽视、身体暴力、身体忽视、家庭物质滥用、言语和情感虐待、家庭功能障碍）在 Y15 时获得。
主要结果由与生物衰老和长期健康相关的 5 种基于 DNA 甲基化的 EAA 测量值组成：内在 EAA（IEAA）、外在 EAA（EEAA）、PhenoAge 加速（PhenoAA）、GrimAge 加速（GrimAA）和 Dunedin 从表观基因组计算的衰老速度（DunedinPACE），在 Y15 和 Y20 时测量。线性回归和广义估计方程用于评估 ACEs 负担（≥4 项与<4 项 ACEs）与 EAA 的关联，调整了人口统计学、健康相关行为以及早期生活和成人社会经济地位。
在排除了缺失数据的参与者后，共有 895 名 Y15 参与者（平均[SD]年龄 40.4[3.5]岁；450 名男性[50.3%]和 445 名女性[49.7%]；319 名黑人[35.6%]和 576 名白人[64.4%]）和 867 名 Y20 参与者（平均[SD]年龄 45.4[3.5]岁；432 名男性[49.8%]和 435 名女性[50.2%]；306 名黑人[35.3%]和 561 名白人[64.7%]）被纳入研究。在 Y15 时有 185 名参与者（20.7%）有 4 项或更多 ACEs，而 710 名参与者（79.3%）没有 4 项或更多 ACEs；在 Y20 时有 179 名参与者（20.6%）有 4 项或更多 ACEs，而 688 名参与者（79.4%）没有 4 项或更多 ACEs。在 Y15 时有 4 项或更多 ACEs 与 EAA 呈正相关，表现为 EEAA 增加 0.60 年（95%CI，0.18-1.02 年）、PhenoAA 增加 0.62 年（95%CI，0.13-1.11 年）、GrimAA 增加 0.71 年（95%CI，0.42-1.00 年）、DunedinPACE 增加 0.01（95%CI，0.01-0.02 年）；在 Y20 时有 4 项或更多 ACEs 与 EAA 呈正相关，表现为 IEAA 增加 0.41 年（95%CI，0.05-0.77 年）、EEAA 增加 1.05 年（95%CI，0.66-1.44 年）、PhenoAA 增加 0.57 年（95%CI，0.08-1.05 年）、GrimAA 增加 0.57 年（95%CI，0.28-0.87 年）、DunedinPACE 增加 0.01（95%CI，0.01-0.02 年），在调整了人口统计学、健康相关行为和社会经济地位后。
在这项队列研究中，ACEs 与中年成年人的 EAA 相关，在控制了人口统计学、行为和社会经济地位后。这些在中年期发现的早期生活经历与生物衰老过程之间的关联，可能有助于从生命历程的角度促进健康。
