Epigenetic clocks are biochemical tests that measure biological age by analyzing DNA methylation (DNAm) patterns—chemical modifications to the genome that regulate gene expression without altering the DNA sequence. Unlike chronological age, which tracks time, biological age serves as a proxy for physiological integrity, predicting morbidity and mortality risks.

Generations of Clocks Epigenetic clocks have evolved through different "generations":

• First-Generation (e.g., Horvath, Hannum): Trained to predict chronological age. They are useful for general age estimation but less sensitive to health status.

• Second-Generation (e.g., PhenoAge, GrimAge): Trained on physiological biomarkers and mortality data. These clocks outperform their predecessors in predicting life expectancy,  ...