Abstract 13085: Accelerated Aging is Associated With Cardiometabolic, Hematologic and Renal Abnormalities: A Project Baseline Health Substudy

Abstract

Background: Genetic methylation patterns correlate with age, but some individuals demonstrate accelerated biologic aging as determined by higher methylation/epigenetic age compared with actual chronologic age. Objective: To determine characteristics of individuals who have accelerated aging (AA). Methods: The Project Baseline Health (PBH) study recruited 2501 participants who underwent multiple assessments (imaging, functional assessments, biospecimens) at enrollment and had annual visits. Methylation profiling (Illumina EPIC) was performed on enrollment blood samples (N=1661); repeat profiling was performed on year 1 blood (N=260). The Horvath method was used to calculate biologic age from methylation data. AA was calculated as the residual of the difference between methylation (i.e. biologic) and chronologic age. Characteristics were compared between low and high AA groups using linear and logistic regression. Results: Of 1661 individuals, 195 were low AA (-14.9 to -5.0 yrs difference in biologic vs chronologic age) and 188 were high AA (5.0 - 17.3 yrs). Discriminating characteristics between high and low AA were sex (60% vs 39% male), uric acid, BMI and waist circumference (all p<0.001, all higher in high AA), and hypertension (37% vs. 27%, p<0.05). Other laboratory variables that were significantly higher in the high AA group included: triglycerides, multiple complete blood count indices, creatinine and ALT (all p<0.05). Lab variables lower in high AA included: HDL cholesterol, 25-OH vitamin D, and glomerular filtration rate (all p<0.05). In a subset (N=260) with repeat methylation, individuals with biologic aging greater than chronologic aging had higher baseline glucose and diastolic blood pressure (p<0.05), and a trend for lower vitamin D (p=0.06). Conclusions: In this Project Baseline Health study, we used deep phenotyping to identify abnormalities associated with accelerated aging. Individuals with high AA had up to a 15 year higher biologic vs. chronologic age and were more often male with greater cardiometabolic, hematologic and renal abnormalities, and lower vitamin D levels. These results highlight factors that may mediate adverse effects of aging and identify targets for mitigation of these effects in future studies.