Association of Epigenetic Metrics of Biological Age with Cortical Thickness

Importance: Magnetic resonance imaging (MRI) studies of aging adults have shown substantial intersubject variability across various brain metrics, and some of this variability is likely attributable to chronological age being an imprecise measure of age-related change. Accurately quantifying one's biological age could allow better quantification of healthy and pathological changes in the aging brain. Objective: To investigate the association of DNA methylation (DNAm)-based biological age with cortical thickness and to assess whether biological age acceleration compared with chronological age captures unique variance in cortical thinning. Design, Setting, and Participants: This cross-sectional study used high-resolution structural brain MRI data collected from a sample of healthy aging adults who were participating in a larger ongoing neuroimaging study that began in May 2014. This population-based study accrued participants from the greater Omaha, Nebraska, metropolitan area. One hundred sixty healthy adults were contacted for the MRI component, 82 of whom participated in both DNAm and MRI study components. Data analysis was performed from March to June 2019. Main Outcomes and Measures: Vertexwise cortical thickness, DNAm-based biological age, and biological age acceleration compared with chronological age were measured. A pair of multivariable regression models were computed in which cortical thickness was regressed on DNAm-based biological age, controlling for sex in the first model and also controlling for chronological age in the second model. Results: Seventy-nine adult participants (38 women; mean [SD] age, 43.82 [14.50] years; age range, 22-72 years) were included in all final analyses. Advancing biological age was correlated with cortical thinning across frontal, superior temporal, inferior parietal, and medial occipital regions. In addition, biological age acceleration relative to chronological age was associated with cortical thinning in orbitofrontal, superior and inferior temporal, somatosensory, parahippocampal, and fusiform regions. Specifically, for every 1 year of biological age acceleration, cortical thickness would be expected to decrease by 0.024 mm (95% CI, -0.04 to -0.01 mm) in the left orbitofrontal cortex (partial r, -0.34; P =.002), 0.014 mm (95% CI, -0.02 to -0.01 mm) in the left superior temporal gyrus (partial r, -0.36; P =.001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the left fusiform gyrus (partial r, -0.38; P =.001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the right fusiform gyrus (partial r, -0.43; P <.001), 0.019 mm (95% CI, -0.03 to -0.01 mm) in the right inferior temporal sulcus (partial r, -0.34; P =.002), and 0.011 mm (95% CI, -0.02 to -0.01 mm) in the right primary somatosensory cortex (partial r, -0.37; P =.001). Conclusions and Relevance: To our knowledge, this is the first study to investigate vertexwise cortical thickness in relation to DNAm-based biological age, and the findings suggest that this metric of biological age may yield additional insight on healthy and pathological cortical aging compared with standard measures of chronological age alone..