Epigenetic age acceleration assessed with human white-matter images

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n=628; age= 23.28 -93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. Weobserved negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρ_pheno= -0.119, p=0.028), with evidence of shared genetic (ρ_gene=-0.463, p=0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypiccorrelationsbetweengranulocyteabundanceandwhitematterintegrity.Thesefindings (i.e., increased acceleration in epigeneticage in peripheral blood correlates withreducedwhite matter integrity in the brainandsharescommongenetic influences) provide awindowinto the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.