How old are you really? Epigenetic clocks – A narrative review

The epigenetic clock, defined by DNA methylation patterns at specific CpG sites, represents one of the most precise molecular biomarkers of biological aging, differentiating it from chronological age by capturing cumulative, systemic epigenetic alterations. Several clock algorithms, including Horvath’s pan-tissue clock, Hannum’s blood-based model, and successive second-generation clocks (e.g., PhenoAge and GrimAge), have demonstrated strong capacity for predicting morbidity, mortality, and functional decline, thus highlighting their clinical relevance. Accelerated epigenetic aging has been linked to abnormal regulation of pathways involving inflammation, metabolism, genomic stability, and mitochondrial function, thereby contributing to the pathogenesis of cardiovascular disease, type 2 diabetes, neurodegeneration, cancer, and other disorders. On the other hand, decelerated epigenetic aging is correlated with enhanced health span. Importantly, epigenetic clocks are increasingly being used to quantify the impact of lifestyle interventions, pharmacological modulators, and experimental age-reversing strategies. Along with clock development, epigenetic reprogramming has emerged as a potential rejuvenation approach, with studies demonstrating that reprogramming can reset epigenetic age, restore mitochondrial and metabolic function, and amend tissue degeneration. The combined action of epigenetic clocks and reprogramming technologies provides a powerful framework for both understanding aging biology and its application in age-related disorders. In clinical contexts, these tools could enable personalized risk stratification, early detection of subclinical pathology, and monitoring of therapeutic efficacy in interventions targeting biological aging. Collectively, epigenetic clocks and reprogramming strategies together have the potential to transform ageing research and pave the way for precision therapeutics in age-related disorders.