Changes in Loneliness, BDNF, and Biological Aging Predict Trajectories in a Blood-Based Epigenetic Measure of Cortical Aging: A Study of Older Black Americans

Abstract

A recent epigenetic measure of aging has developed based on human cortex tissue. This cortical clock (CC) dramatically outperformed extant blood-based epigenetic clocks in predicting brain age and neurological degeneration. Unfortunately, measures that require brain tissue are of limited utility to investigators striving to identify everyday risk factors for dementia. The present study investigated the utility of using the CpG sites included in the CC to formulate a peripheral blood-based cortical measure of brain age (CC-Bd). To establish the utility of CC-Bd, we used growth curves with individually varying time points and longitudinal data from a sample of 694 aging African Americans. We examined whether three risk factors that have been linked to cognitive decline—loneliness, depression, and BDNFm—predicted CC-Bd after controlling for several factors, including three new-generation epigenetic clocks. Our findings showed that two clocks—DunedinPACE and PoAm—predicted CC-BD, but that increases in loneliness and BDNFm continued to be robust predictors of accelerated CC-Bd even after taking these effects into account. This suggests that CC-Bd is assessing something more than the pan-tissue epigenetic clocks but that, at least in part, brain health is also associated with the general aging of the organism.