Association of Epigenetic Aging with Cognitive Aging in Diverse Hispanics/Latinos

Abstract

AbstractBackgroundAge‐related DNA methylation (DNAm) changes occur in specific regions of the genome and have been shown to be correlated with an individual’s chronological age. Multiple “epigenetic clocks” have been developed to estimate an individual’s DNAm age, which reflect different aspects of the multidimensional aging process. Age acceleration, the deviation of the DNAm‐estimated age from the chronological age, has been proposed as a novel biomarker of aging. We investigated the association between multiple measures of age acceleration and cognitive aging phenotypes in diverse Hispanic and Latino adults.MethodsWe estimated epigenetic age acceleration from 5 epigenetic clocks in 2188 Hispanic and Latino adults (mean age 56.7 years; 64.6% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) who had available blood DNA methylation data at the baseline visit and neurocognitive data. These included first generation clocks, Horvath and Hannum clocks; second generation PhenoAge and GrimAge; and third generation DunedinPACE (Pace of Aging). We used mixed models to test the association of each of these measures with a global measure of cognitive function (PC1) at the baseline visit and with mild cognitive impairment at a follow‐up visit approximately 7 years later.ResultsThere were significant cross‐sectional associations between lower global cognitive function and greater age acceleration based on Hannum, Horvath, PhenoAge, and DunedinPACE algorithms. In addition, a greater age acceleration based on DunedinPACE was strongly associated with a higher risk of MCI 7 years later (Table).ConclusionBiological aging is associated with lower cognitive function and risk of MCI in diverse Hispanic and Latino adults. DunedinPACE, a third generation epigenetic clock, may be a more sensitive predictor of cognitive aging outcomes than previous generation clocks.