Development of a novel aging clock based on chromatin accessibility

Abstract

The establishment of aging clocks based on age-associated changes in DNA methylation has highlighted the strong link between epigenetic alterations and aging. However, the connection between DNA methylation changes at clock sites and their effect on cellular function remains unclear. We hypothesize that chromatin accessibility, a readout that integrates multiple epigenetic mechanisms, may connect epigenetic changes with downstream biological effects. To investigate this hypothesis, we generated chromatin accessibility profiles from peripheral blood mononuclear cells (PBMCs) of 157 human donors and construct a novel aging clock with a median absolute error on prediction of 5.69 years. Moreover, by comparing our chromatin accessibility data to matched transcriptomic profiles, we show that the genomic sites selected for the prediction of age based on chromatin accessibility undergo transcriptional changes during aging. This chromatin accessibility clock could therefore be used to investigate the direct effect of aged epigenetic states on cellular function.