Evaluation of different computational methods for DNA methylation-based biological age

In recent years there has been a widespread interest in researching biomarkers of aging that could predict physiological vulnerability better than chronological age. Aging, in fact, is one of the most relevant risk factors for a wide range of maladies, and molecular surrogates of this phenotype could enable better patients stratification. Among the most promising of such biomarkers is DNA methylation-based biological age. Given the potential and variety of computational implementations (epigenetic clocks), we here present a systematic review of such clocks. Furthermore, we provide a large-scale performance comparison across different tissues and diseases in terms of age prediction accuracy and age acceleration, a measure of deviance from physiology. Our analysis offers both a state-of-the-art overview of the computational techniques developed so far and a heterogeneous picture of performances, which can be helpful in orienting future research.