Department of Medical Gerontology, Trinity College Dublin, Ireland.
Department of Biomedical Sciences, University of Sassari, Italy.
Psychoneuroendocrinology. 2022 Mar;137:105643. doi: 10.1016/j.psyneuen.2021.105643. Epub 2021 Dec 23.
This retrospective cross-sectional study was designed to explore whether the experience of childhood adversity was associated with epigenetic age acceleration in mid-life and older ages using the next generation GrimAge and Pace of Aging DNA methylation clocks.
The study involved a sub-sample of 490 individuals aged 50-87 years of age participating in the Irish Longitudinal Study on Aging (TILDA); a large nationally representative prospective cohort study of aging in Ireland. Childhood adversity was ascertained via self-report using 5-items that were deemed to indicate potentially nefarious childhood exposures, including growing up poor, death of a parent, parental substance abuse in the family, childhood physical abuse, and childhood sexual abuse.
Only childhood poverty was associated with significant epigenetic age acceleration according to the GrimAge and Pace of Aging clocks, hastening biological aging by 2.04 years [CI= 1.07, 3.00; p < 0.001] and 1.16 years [CI= 0.11, 2.21; p = 0.030] respectively. Analysis of the dose-response pattern revealed each additional adversity was associated with 0.69 years of age acceleration [CI= 0.23, 1.15; p = 0.004] according to the GrimAge clock. Mediation analysis suggested that lifetime smoking explains a substantial portion (>50%) of the excess risk of age acceleration amongst those who experienced childhood poverty.
This study adds to the growing body of evidence which implicates early life adversity, particularly deprivation as a potential precipitant of earlier biological aging, and implicates smoking-related changes to DNA methylation processes as a candidate pathway and mechanism through which the social environment gets transduced at a biological level to hasten the aging process.
本回顾性横断面研究旨在使用下一代 GrimAge 和衰老 DNA 甲基化时钟探讨中年和老年时期经历童年逆境是否与表观遗传年龄加速有关。
该研究涉及参与爱尔兰老龄化纵向研究(TILDA)的 490 名年龄在 50-87 岁的个体的子样本;这是一项在爱尔兰进行的大型全国代表性前瞻性衰老队列研究。童年逆境通过使用 5 项被认为表明潜在有害的童年暴露的自我报告来确定,包括在贫困中长大、父母去世、家庭中父母滥用药物、儿童身体虐待和儿童性虐待。
只有童年贫困与 GrimAge 和衰老时钟的显著表观遗传年龄加速有关,根据 GrimAge 时钟加速生物衰老 2.04 年[CI=1.07, 3.00;p<0.001]和 1.16 年[CI=0.11, 2.21;p=0.030]。对剂量反应模式的分析表明,根据 GrimAge 时钟,每增加一次逆境与 0.69 年的年龄加速有关[CI=0.23, 1.15;p=0.004]。中介分析表明,终生吸烟解释了经历童年贫困的人加速年龄的大部分(>50%)超额风险。
这项研究增加了越来越多的证据,这些证据表明早期生活逆境,特别是贫困,可能是更早的生物衰老的一个潜在诱因,并暗示与吸烟相关的 DNA 甲基化过程的变化是一种潜在的途径和机制,通过这种途径和机制,社会环境在生物学水平上被转化,从而加速衰老过程。