Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife.
Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife.
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DOI：
10.1001/jamanetworkopen.2023.17987
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发表时间：
2023-06-01
影响因子：
13.8
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中科院分区：
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这项队列研究调查了儿童不良经历与15至20年随访的5种基于DNA甲基化的加速表观遗传老化措施的相关性。有不良童年经历(ACE)的人是否在中年加速了表观遗传年龄？在这项队列研究中，对895名15岁的成年人和867名20岁的成年人进行了DNA甲基化分析的随访，拥有4个或更多A的参与者可能与他们早期或晚年的社会经济地位无关的表观遗传年龄比他们的实际年龄更大。ACE与各种表观遗传年龄加速测量一致相关。这项研究的发现表明，ACE的高负担与多个表观遗传年龄加速测量之间的一致关联表明，ACE可能与晚年的生物衰老过程持续相关。不良童年经历(ACE)与较差的健康风险相关，识别分子机制可能为ACE患者的健康促进奠定基础。在种族和性别人口结构平衡的人群中，研究ACE与表观遗传年龄加速(EAA)变化的关系，表观遗传年龄加速(EAA)是一种与中年人各种健康结果相关的生物标志物。这项队列研究的数据来自青年冠状动脉风险发展(CARDIA)研究。CARDIA的参与者从基线(0年[Y0]；1985-1986)到30年(2015-2016)进行了8次随访检查，并在15年(2000-2001)和20年(2005-2006年)获得了参与者的血液DNA甲基化信息。来自Y15和Y20的个体具有可用的DNA甲基化数据和完整的ACE和协变量变量。分析了2021年9月至2022年8月的数据。在第15年获得参与者ACES(一般疏忽、情感疏忽、身体暴力、身体疏忽、家庭物质滥用、言语和情感虐待、家庭功能障碍)。主要结果包括5项已知与生物老化和长期健康相关的基于DNA甲基化的EAA测量结果：内在EAA(IEAA)、外部EAA(EEAA)、表观年龄加速(PhenoAA)、GrimAA(GrimAA)和根据表观基因组计算的Dunedin Pace of Aging(DunedinPACE)，测量时间分别为15年和20年。使用线性回归和广义估计方程来评估ACEs的负担(≥4vs4ACEs)与调整人口统计学、健康相关行为、早期生活和成人社会经济状况的EAA之间的关系。剔除数据缺失的参与者后，15岁的895名参与者(平均年龄40.4[3.5]岁；男性450名[50.3%]和女性445名[49.7%]；黑人319名[35.6%]和白人576名[64.4%])和20岁的867名参与者(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%])。在第15年，185名参与者(20.7%)与710名参与者(79.3%)没有4个或更多ACE；179名参与者(20.6%)与688名参与者(79.4%)在20岁时没有4个或更多ACE。有4个或4个以上的ACE值与15岁(β = 0.60岁；95%CI，0.18-1.02岁；PhenoAA：β = 0.62岁；95%CI = 0.13-1.11年；GrimAA：β = 0.71年；95%CI，0.42-1.00岁；达尼丁PACE：β = 0.01；95%CI，0.01-0.02)和Y20年(IEAA：β = 0.41年；调整人口学、健康相关行为和社会经济状况后，95%可信区间为0.0 5年，95%可信区间为0.0 5岁；95%可信区间为0.66~1.44岁；β = 为0.5 7年；95%可信区间为0.0 8~1.0 5年；β = 为0.5 7年；95%可信区间为0.2 8~0.87岁；达尼丁PACE为0.0 1；95%可信区间为0.0 1~0.0 2。在这项队列研究中，在控制了人口统计学、行为和社会经济地位后，在中年人中，ACE与EAA相关。这些早期生活经验与中年生物衰老过程之间的关联的发现可能有助于从生命过程的角度促进健康。
This cohort study investigates the association of adverse childhood experiences with 5 DNA methylation–based measures of accelerated epigenetic aging at 15 to 20 years of follow-up. Do individuals with adverse childhood experiences (ACEs) have accelerated epigenetic age in their midlife? In this cohort study of 895 adults at year 15 and 867 adults at year 20 of follow-up with DNA methylation profiling, participants with 4 or more ACEs were likely to have older epigenetic ages compared with their chronological ages independently of their socioeconomic status in early or later life. ACEs was consistently associated with various epigenetic age acceleration measurements. This study’s findings of consistent associations between a high burden of ACEs and multiple epigenetic age acceleration measurements suggest that ACEs may be persistently associated with the biological aging process in later life. 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. 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.