Evolutionary Epigenetic Analysis of Oxidative Balance Score-Associated DNA Methylation Sites Across Mammals

Oxidative Balance Score (OBS) summarizes diet- and lifestyle-related exposures relevant to redox homeostasis, but the evolutionary behavior of OBS-associated epigenetic markers remains unclear. In this study, we conducted a covariate-adjusted epigenome-wide association study (EWAS) in Korean Genome and Epidemiology Study (KoGES) cohorts, adjusting for OBS and cell-type proportions. We identified 26 robust OBS-associated CpG sites. We then mapped these loci to the Mammalian Methylation Consortium dataset (GSE223748) and examined age-related methylation dynamics across nine mammalian species, using chronological age as a proxy for cumulative oxidative burden. Cross-species analyses showed that human correlation patterns were only partially preserved, with greater concordance observed in primates than in several non-primate species. Furthermore, 1000-iteration bootstrap resampling and null-model sensitivity analyses (Robinson-Foulds distance) demonstrated that the interspecies clustering topology of these 26 CpGs is statistically robust and distinct from random genomic noise. These findings suggest partial evolutionary preservation of age-related methylation behavior at human OBS-associated loci, providing a comparative framework for redox-related epigenetic dynamics.