Chan Jonathan, Rubbi Liudmilla, Pellegrini Matteo
Computational and Systems Biology Interdepartmental Program at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Aging (Albany NY). 2025 Mar 12;17(3):685-698. doi: 10.18632/aging.206220.
The dynamic nature of epigenetic modifications has been leveraged to construct epigenetic clocks that accurately predict an individual's age based on DNA methylation levels. Here we explore whether the accumulation of epimutations, which can be quantified by Shannon's entropy, changes reproducibly with age. Using targeted bisulfite sequencing, we analyzed the associations between age, entropy, and methylation levels in human buccal swab samples. We find that epigenetic clocks based on the entropy of methylation states predict chronological age with similar accuracy as common approaches that are based on methylation levels of individual cytosines. Our approach suggests that across many genomic loci, methylation entropy changes reproducibly with age.
表观遗传修饰的动态特性已被用于构建表观遗传时钟,该时钟可根据DNA甲基化水平准确预测个体年龄。在此,我们探讨表观突变的积累(可通过香农熵进行量化)是否会随年龄发生可重复的变化。我们使用靶向亚硫酸氢盐测序技术,分析了人类口腔拭子样本中年龄、熵和甲基化水平之间的关联。我们发现,基于甲基化状态熵的表观遗传时钟预测实际年龄的准确性与基于单个胞嘧啶甲基化水平的常用方法相似。我们的方法表明,在许多基因组位点上,甲基化熵会随年龄发生可重复的变化。