Accelerated Epigenetic Aging is Associated with Multiple Cardiometabolic, Hematologic and Renal Abnormalities: a Project Baseline Health Substudy

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  • Background: Epigenetic clocks estimate chronologic age using methylation levels at specific loci. Accelerated biologic aging, defined as higher epigenetic age compared with chronologic age, is associated with adverse health outcomes and mortality. We tested the hypothesis that individuals demonstrating accelerated aging have a wide range of disease trait abnormalities. Methods: The Project Baseline Health Study recruited 2502 participants for longitudinal deep phenotyping, including 1661 with Horvath epigenetic age estimates at enrollment. We calculated epigenetic age acceleration (EAA) as the residual of epigenetic age regressed on chronologic age, and classified individuals with high or low extremes of EAA. A subset of 260 participants with methylation profiling at 1-year were categorized as larger or smaller than expected over this time. Using a set of 122 clinical and laboratory variables, we created phenoclusters using principal components analysis. Using logistic regression models adjusted for sex, we tested individual variables and phenoclusters between individuals with low vs. high EAA, and between individuals with accelerated vs. non-accelerated aging over one year. Results: The high EAA group (n=188) had epigenetic age estimates 5-17 years older than expected, while the low EAA group (n=195) had estimates 5-15 years younger than expected. Individuals in the high EAA group had higher triglycerides, neutrophils, wbcs, uric acid, BMI, grip strength, hypertension, and phenoclusters summarizing lung function and lipids; the high EAA group had lower values for HDL, albumin, eGFR, step count, and phenoclusters representing physical fitness and ocular health. In longitudinal analysis, 148 participants showed accelerated aging and had higher glucose levels and diastolic blood pressure compared to 112 individuals without accelerated aging. Conclusions: We report multiple cardiometabolic, hematologic, and renal features characterizing individuals with EAA. These highlight potential factors that may mediate the adverse effects of aging and identify potential targets for mitigation of these effects in future studies.
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  • 0000-0002-0027-6483
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