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加拿大老龄化纵向研究(CLSA)中不良儿童经历与表观遗传年龄加速的关联。

The association between adverse childhood experiences and epigenetic age acceleration in the Canadian longitudinal study on aging (CLSA).

机构信息

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Labarge Centre for Mobility in Aging, McMaster University, Hamilton, Ontario, Canada.

出版信息

Aging Cell. 2023 Feb;22(2):e13779. doi: 10.1111/acel.13779. Epub 2023 Jan 17.

Abstract

Research examining the association between exposure to a wide range of adverse childhood experiences (ACEs) and accelerated biological aging in older adults is limited. The purpose of this study was to examine the association of ACEs, both as a cumulative score and individual forms of adversity, with epigenetic age acceleration assessed using the DNA methylation (DNAm) GrimAge and DNAm PhenoAge epigenetic clocks in middle and older-aged adults. This cross-sectional study analyzed baseline and first follow-up data on 1445 participants aged 45-85 years from the Canadian Longitudinal Study on Aging (CLSA) who provided blood samples for DNAm analysis. ACEs were assessed using a validated self-reported questionnaire. Epigenetic age acceleration was estimated by regressing each epigenetic clock estimate on chronological age. Cumulative ACEs score was associated with higher DNAm GrimAge acceleration (β: 0.07; 95% CI: 0.02, 0.11) after adjusting for covariates. Childhood exposure to parental separation or divorce (β: 0.06; 95% CI: 0.00, 0.11) and emotional abuse (β: 0.06; 95% CI: 0.00, 0.12) were associated with higher DNAm GrimAge acceleration after adjusting for other adversities and covariates. There was no statistical association between ACEs and DNAm PhenoAge acceleration. Early life adversity may become biologically embedded and lead to premature biological aging, in relation to DNAm GrimAge, which estimates risk of mortality. Strategies that increase awareness of ACEs and promote healthy child development are needed to prevent ACEs.

摘要

研究考察了广泛的不良童年经历 (ACEs) 暴露与老年人加速生物学衰老之间的关联,但相关研究有限。本研究旨在探讨 ACEs 与表观遗传年龄加速之间的关联,既包括 ACEs 的累积评分,也包括各种形式的逆境,采用 DNA 甲基化 (DNAm) GrimAge 和 DNAm PhenoAge 表观遗传时钟评估中年和老年成年人的表观遗传年龄加速。这项横断面研究分析了来自加拿大老龄化纵向研究 (CLSA) 的 1445 名 45-85 岁参与者的基线和第一次随访数据,这些参与者提供了用于 DNAm 分析的血液样本。使用经过验证的自我报告问卷评估 ACEs。通过将每个表观遗传时钟估计值与实际年龄进行回归来估计表观遗传年龄加速。在调整协变量后,累积 ACEs 评分与更高的 DNAm GrimAge 加速相关 (β:0.07;95%置信区间:0.02,0.11)。在调整其他逆境和协变量后,童年时期经历父母分居或离婚 (β:0.06;95%置信区间:0.00,0.11) 和情感虐待 (β:0.06;95%置信区间:0.00,0.12) 与更高的 DNAm GrimAge 加速相关。ACEs 与 DNAm PhenoAge 加速之间没有统计学关联。早期生活逆境可能会在生理上根深蒂固,并导致与 DNAm GrimAge 相关的过早生物学衰老,该估计值可以预测死亡率风险。需要采取增加对 ACEs 的认识和促进儿童健康发展的策略来预防 ACEs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fe/9924940/2d0ee878ee27/ACEL-22-e13779-g002.jpg

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