Epigenetic ageing clocks: statistical methods and emerging computational challenges

Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and emerging single-cell methods, aiming to provide guidelines for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.