Epigenetic age acceleration in peripheral blood correlates with brain-MRI age acceleration

Abstract

As the world's population ages, more and more people are expected to suffer from age-related diseases. Biological aging markers derived from DNA methylation and brain structure show promise in predicting health outcomes. Understanding the relationship between these biomarkers can promote the development of effective health interventions. In a sample of 254 participants from the Netherlands Twin Register (20-84 years), we investigated associations between DNA methylation age acceleration based on five epigenetic biomarkers (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPACE) and brain age acceleration based on neuroimaging (brainageR). Furthermore, we applied bivariate twin models to examine the contribution of genetic and environmental factors to the associations (cross-twin cross-trait correlations and within monozygotic-twin pair differences). We observed relationships with brain age acceleration for DNA methylation age acceleration based on the Hannum and GrimAge clocks that were supported by within MZ twin pair difference modelling. Cross-twin cross-trait modelling confirmed a non-shared environmental etiology. Twin analyses highlight the importance of the environment in accelerated aging, raising the possibility for interventions such as lifestyle modification.