Earlier pubertal timing is associated with accelerated epigenetic aging, but the underlying mechanisms are not well understood. This three-wave longitudinal study examined negative health behaviors, specifically substance use, short sleep duration, and poor diet quality in middle adolescence, as mediators of links between earlier phenotypic and perceived pubertal timing measured in early adolescence and epigenetic aging on three epigenetic clocks in late adolescence (GrimAge, DunedinPACE, and PhenoAge). Phenotypic pubertal timing measured physical pubertal maturation relative to chronological age, whereas perceived pubertal timing was based on adolescents’ subjective interpretation of their pubertal timing relative to their peers. Participants included 1213 youth (51% female, 49% male; 62% Black, 34% White) who participated during early adolescence (mean age = 13.10 years), middle adolescence (mean age = 16.1 years) and late adolescence (mean age = 19.7 years). Results from a mediation model revealed a mediation effect of earlier phenotypic pubertal timing on accelerated GrimAge in late adolescence through higher substance use during middle adolescence. There was also a direct effect of earlier phenotypic pubertal timing on accelerated DunedinPACE in males. Sleep duration and diet quality did not emerge as mediators but shorter sleep duration predicted accelerated GrimAge in females. These findings suggest that higher substance use presents a mechanism through which earlier maturing youth experience faster epigenetic aging that puts them at risk for poorer health across the lifespan.

较早的青春期时间与加速的表观遗传衰老有关，但其潜在机制尚不清楚。这项三波纵向研究检查了负面健康行为，特别是青春期中期的物质使用、睡眠时间短和饮食质量差，作为青春期早期测量的早期表型和感知的青春期时间与青春期晚期三个表观遗传时钟（GrimAge、DunedinPACE 和 PhenoAge）的表观遗传衰老之间联系的中介。表型青春期时间测量的是相对于实际年龄的身体青春期成熟度，而感知的青春期时间是基于青少年相对于同龄人对青春期时间的主观解释。参与者包括 1213 名青年 （51% 女性，49% 男性;62% 黑人，34% 白人），他们在青春期早期 （平均年龄 = 13.10 岁）、青春期中期 （平均年龄 = 16.1 岁） 和青春期晚期 （平均年龄 = 19.7 岁） 参与。中介模型的结果揭示了早期表型青春期时间对青春期晚期加速 GrimAge 到青春期中期物质使用增加的中介作用。早期表型青春期时间对男性加速的 DunedinPACE 也有直接影响。睡眠时间和饮食质量并未成为中介，但较短的睡眠时间预示着女性的 GrimAge 加速。这些发现表明，较高的物质使用呈现出一种机制，通过这种机制，较早成熟的青年会经历更快的表观遗传衰老，这使他们在整个生命周期中面临健康状况较差的风险。