ABSTRACT
We present a systematic analysis of epigenetic age acceleration based on by far the largest collection of publicly available DNA methylation data for healthy samples (93 datasets, 23â¯K samples), focusing on the geographic (25 countries) and ethnic (31 ethnicities) aspects around the world. We employed the most popular epigenetic tools for assessing age acceleration and examined their quality metrics and ability to extrapolate to epigenetic data from different tissue types and age ranges different from the training data of these models. In most cases, the models proved to be inconsistent with each other and showed different signs of age acceleration, with the PhenoAge model tending to systematically underestimate and different versions of the GrimAge model tending to systematically overestimate the age prediction of healthy subjects. Referring to data availability and consistency, most countries and populations are still not represented in GEO, moreover, different datasets use different criteria for determining healthy controls. Because of this, it is difficult to fully isolate the contribution of "geography/environment", "ethnicity" and "healthiness" to epigenetic age acceleration. Among the explored metrics, only the DunedinPACE, which measures aging rate, appears to adequately reflect the standard of living and socioeconomic indicators in countries, although it has a limited application to blood methylation data only. Invariably, by epigenetic age acceleration, males age faster than females in most of the studied countries and populations.