Jopling Ellen, Drury Stacy S, Fox Nathan A, Zeanah Charles H, Nelson Charles A
Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
Laboratories of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, Boston, MA 02445.
Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2504216122. doi: 10.1073/pnas.2504216122. Epub 2025 Jun 30.
A stable caregiving environment early in life is essential for children's development, and disruptions have the potential to impact biological processes. Using data from the Bucharest Early Intervention Project, we examined a developmental cascade model in which shifts in pubertal tempo following early caregiving disruptions come at an epigenetic cost. Among 115 individuals, all of whom experienced severe deprivation early in life, we tracked caregiving disruptions across childhood; assessed pubertal timing and tempo across adolescence; and quantified the pace of cellular aging via telomere erosion across the second decade of life. We demonstrate that a greater number of caregiving disruptions is associated with delayed pubertal timing and an acceleration of pubertal tempo. In turn, accelerations in pubertal tempo are associated with significantly greater telomere erosion across time. A formal mediation model indicated that greater caregiving disruptions during childhood predicted greater telomere erosion through an acceleration of pubertal tempo. By documenting the impact of caregiving disruptions on pubertal development and ultimately biological aging, these findings highlight the importance of the stability of the caregiving context and the critical need to ensure that organizations caring for vulnerable children establish programs and policies to minimize unnecessary disruptions.
生命早期稳定的照料环境对儿童发育至关重要，而环境干扰有可能影响生物过程。利用布加勒斯特早期干预项目的数据，我们研究了一种发育级联模型，其中早期照料干扰后青春期节奏的变化会带来表观遗传学代价。在115名个体中，所有人在生命早期都经历了严重剥夺，我们追踪了他们童年时期的照料干扰情况；评估了整个青春期的青春期时间和节奏；并通过测量生命第二个十年中因端粒侵蚀导致的细胞衰老速度进行量化。我们证明，更多的照料干扰与青春期时间延迟和青春期节奏加快有关。反过来，青春期节奏加快又与随着时间推移端粒侵蚀显著加剧有关。一个正式的中介模型表明，童年时期更多的照料干扰通过加速青春期节奏预示着更大程度的端粒侵蚀。通过记录照料干扰对青春期发育以及最终对生物衰老的影响，这些发现凸显了照料环境稳定性的重要性，以及确保照顾弱势儿童的机构制定项目和政策以尽量减少不必要干扰的迫切需求。
