Human epigenetic ageing is logarithmic with time across the entire lifespan

Epigenetic changes during ageing have been characterized by multiple epigenetic clocks that allow the prediction of chronological age based on methylation status. Despite their accuracy and utility, epigenetic age biomarkers leave many questions about epigenetic ageing unanswered. Specifically, they do not permit the unbiased characterization of non-linear epigenetic ageing trends across entire life spans, a critical question underlying this field of research. Here we provide an integrated framework to address this question. Our model, inspired from evolutionary models, is able to account for acceleration/deceleration in epigenetic changes by fitting an individual’s model age, the epigenetic age, which is related to chronological age in a non-linear fashion. Application of this model to DNA methylation data measured across broad age ranges, from before birth to old age, and from two tissue types, suggests a universal logarithmic trend characterizes epigenetic ageing across entire lifespans.

衰老过程中的表观遗传变化已通过多种表观遗传时钟（epigenetic clock）得到表征，这些时钟可基于甲基化状态预测个体的实足年龄。尽管这类表观遗传年龄生物标志物具备准确性与实用价值，但仍有诸多关于表观遗传衰老（epigenetic ageing）的问题尚未得到解答。具体而言，它们无法对全生命周期内的非线性表观遗传衰老趋势进行无偏表征，而这正是该研究领域的核心问题。为此，我们提出了一个整合性框架以解决这一问题。我们的模型受进化模型启发，通过拟合个体的模型年龄——即表观遗传年龄——来阐释表观遗传变化的加速与减速现象；该表观遗传年龄与实足年龄呈非线性相关关系。我们将该模型应用于覆盖从产前至老年的宽泛年龄跨度、且源自两种组织类型的DNA甲基化（DNA methylation）数据后，结果表明，一条普适性对数趋势刻画了全生命周期内表观遗传衰老的整体特征。