DNAm clocks and pace-of-aging measures
DNAm clocks are algorithms that combine information from DNAm measurements across the genome to quantify variation in biological ageThe first-generation DNAm clocks were developed from machine-learning analyses comparing samples from individuals of different chronological age. These clocks were highly accurate in predicting the chronological age of new samples and also showed some capacity for predicting differences in mortality risk, although effect sizes tend to be small and inconsistent across studiesThe second-generation DNAm clocks were developed with the goal of improving quantification of biological aging by focusing on differences in mortality risk instead of on differences in chronological ageA limitation of several DNAm clocks is that when residualized for chronological age, values show only moderate test–retest reliability across technical replicates. Test–retest reliability is a critical feature of measurements used to evaluate the impact of intervention because change from preintervention to postintervention cannot be distinguished from technical noise unless reliability is high. To improve technical reliability, Higgins-Chen and colleagues developed a new computational method that retrained DNAm clocks using DNAm PCsA third generation of DNAm measures of aging are referred to as pace-of-aging measures. In contrast to first- and second-generation DNAm clocks, which aim to quantify how much aging has occurred up to the time of measurement, pace-of-aging measures aim to quantity how fast the process of aging-related deterioration of system integrity is proceeding. We analyzed the newest pace-of-aging measure, DunedinPACE, which is shorthand for ‘Pace of Aging Computed from the Epigenome’Our primary analysis focused on the PC versions of the PhenoAge and GrimAge second-generation clocks and DunedinPACE, all of which show exceptional test–retest reliability in technical replicates. We report results for both original and PC versions of DNAm clocks in the 