Khodasevich Dennis, Bozack Anne K, Daredia Saher, Deardorff Julianna, Harley Kim G, Eskenazi Brenda, Guo Weihong, Holland Nina, Cardenas Andres
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
Division of Epidemiology, Berkeley Public Health, University of California, Berkeley, CA, USA.
Epigenetics. 2025 Dec;20(1):2503824. doi: 10.1080/15592294.2025.2503824. Epub 2025 May 16.
Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of and across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.
早期生命中的表观遗传衰老特征仍不明确，而基因表达模式可以提供具有生物学意义的见解。在来自CHAMACOS队列的174名青少年参与者（年龄范围：14 - 15岁）中，使用Illumina EPICv1.0芯片测量血液DNA甲基化，并对血液进行RNA测序。计算了13个广泛使用的表观遗传时钟，并使用该流程测试了它们与全转录组RNA表达的关联。我们发现不同表观遗传时钟之间与RNA表达存在大量共同关联的证据，包括在五个时钟中某些基因的差异表达。epiTOC2、主成分（PC）PhenoAge、Hannum、PedBE和PC Hannum时钟与数量最多的RNA差异表达相关，分别与22、8、5、3和2个转录本存在关联。一般来说，生物钟与差异表达的基因数量比按时间顺序计算的时钟更多，并且PC时钟相对于其基于CpG训练的对应时钟与更多基因的差异表达相关。我们研究中的总共17种关联在一个独立的成人样本（年龄范围：40 - 54岁）中得到了重复验证。我们的研究结果支持表观遗传时钟在青少年中的生物学相关性，并为青少年研究中表观遗传衰老生物标志物的选择提供了方向。
