Barr Emily, Comtois-Cabana Maude, Coope Andressa, Coté Sylvana M, Kobor Michael S, Konwar Chaini, Lupien Sonia, Geoffroy Marie-Claude, Boivin Michel, Provençal Nadine, Catherine Nicole L A, Dennis Jessica K, Ouellet-Morin Isabelle
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada.
Biomolecules. 2025 Jun 18;15(6):887. doi: 10.3390/biom15060887.
Youth exposed to early-life adversity (ELA) are at greater risk for poorer physical and mental health outcomes in adolescence and adulthood. Although the biological mechanisms underlying these associations remain elusive, DNA methylation (DNAm) has emerged as a potential pathway. DNAm-based measures of epigenetic age have been associated with ELA, indicating accelerated aging. According to the stress sensitization hypothesis, prenatal adversity may further heighten sensitivity to subsequent stressors in childhood and adolescence. This study examined the associations between ELA and six epigenetic aging measures, considering both the timing of adversity and the participant's sex. Data were drawn from the Quebec Longitudinal Study of Child Development, with two cumulative indices of ELA derived from prospectively collected data: the Perinatal Adversity and the Child and Adolescent Adversity indices. Higher Perinatal Adversity scores were associated with accelerated DunedinPACE scores. No significant associations were found between ELA and the other epigenetic clocks, nor did we find support for the stress sensitization hypothesis-though a sex-specific trend emerged among girls. The findings suggest that DunedinPACE may be more sensitive to variations in ELA than other clocks. Future research should systematically investigate sex-dimorphic associations between ELA and epigenetic aging, with particular attention to the impact of perinatal adversity.
早年经历过逆境(ELA)的青少年在青春期和成年期出现较差身心健康结果的风险更高。尽管这些关联背后的生物学机制仍不清楚,但DNA甲基化(DNAm)已成为一条潜在途径。基于DNAm的表观遗传年龄测量与ELA有关,表明加速衰老。根据应激敏感化假说,产前逆境可能会进一步提高儿童期和青春期对后续应激源的敏感性。本研究考察了ELA与六种表观遗传衰老测量之间的关联,同时考虑了逆境发生的时间和参与者的性别。数据来自魁北克儿童发展纵向研究,从前瞻性收集的数据中得出两个ELA累积指数:围产期逆境指数和儿童及青少年逆境指数。围产期逆境得分越高,与加速的达尼丁PACE得分相关。未发现ELA与其他表观遗传时钟之间存在显著关联,我们也未找到应激敏感化假说的证据——尽管在女孩中出现了性别特异性趋势。研究结果表明,达尼丁PACE可能比其他时钟对ELA的变化更敏感。未来的研究应系统地调查ELA与表观遗传衰老之间的性别差异关联,尤其要关注围产期逆境的影响。