Perez-Correa Juan-Felipe, Stiehl Thomas, Marioni Riccardo E, Corley Janie, Cox Simon R, Costa Ivan G, Wagner Wolfgang
Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
Genome Biol. 2025 Apr 22;26(1):103. doi: 10.1186/s13059-025-03562-1.
Epigenetic aging signatures provide insights into human aging, but traditional clocks rely on linear regression of DNA methylation levels, assuming linear trajectories. This study explores a non-parametric approach using 2D-kernel density estimation to determine epigenetic age. Our weighted model achieves similar predictive accuracy as conventional clocks and provides a variation score reflecting the inherent variability of age-related epigenetic changes within samples. This score is significantly increased in various diseases and associated with mortality risk in the Lothian Birth Cohort 1921. Thus, weighted 2D-kernel density estimation facilitates accurate epigenetic age predictions and offers an additional variable for biological age estimation.
表观遗传衰老特征为人类衰老提供了见解，但传统的时钟依赖于DNA甲基化水平的线性回归，假设其轨迹是线性的。本研究探索了一种使用二维核密度估计的非参数方法来确定表观遗传年龄。我们的加权模型实现了与传统时钟相似的预测准确性，并提供了一个变异分数，反映了样本中与年龄相关的表观遗传变化的固有变异性。在各种疾病中，这个分数显著增加，并且与1921年洛锡安出生队列中的死亡风险相关。因此，加权二维核密度估计有助于准确的表观遗传年龄预测，并为生物年龄估计提供了一个额外的变量。
