Abstract P1008: A blood biomarker of accelerated aging associates with cardiometabolic biomarkers in response to weight-loss dietary interventions

Introduction: Weight-loss diets have shown protective effects on biological aging and cardiometabolic health. A novel epigenetic aging measure, DunedinPACE, is associated with cardiometabolic disorders. Studies examining the associations between DunedinPACE and cardiometabolic biomarkers in response to weight-loss dietary intervention are lacking. Hypothesis: Weight-loss dietary interventions may attenuate the associations between DunedinPACE and cardiometabolic biomarkers. Methods: We included 148 participants with obesity, who participated in a 12-month randomized weight-loss dietary intervention trial, the Study of Macronutrients and Heart Disease Risk (MACRO) trial. DunedinPACE was calculated by llumina EPIC array DNA methylation data from blood, reflecting biological aging at pre-intervention baseline, and pro-intervention 3- and 12-month follow-up. Generalized linear regression models and mixed effect models were used to assess the association between DunedinPACE and cardiometabolic biomarkers. A two-tailed P value of <0.004 (0.05/12) was considered statistically significant after Bonferroni correction. Results: Prior to dietary intervention, every 10% higher DunedinPACE was significantly associated with worse levels of insulin (β: 0.202; standard error [SE]: 0.043; P<0.001), homeostatic model assessment for insulin resistance (β: 0.170; SE: 0.037; P<0.001), high-density lipoprotein cholesterol (β: -0.059; SE: 0.019; P=0.003), adiponectin (β: -0.153; SE: 0.047; P=0.001), and C-reactive protein (β: 0.172; SE: 0.055; P=0.002), adjusting for age, sex, race, and body mass index ( Table ). In response to weight-loss dietary interventions, most associations between DunedinPACE and cardiometabolic biomarkers were attenuated to insignificant levels (P>0.004), except for C-reactive protein (β: 0.205; SE: 0.045; P<0.001) and Ghrelin (β: -0.076; SE: 0.020; P<0.001). Conclusions: Our findings indicate that DunedinPACE was associated with worse cardiometabolic biomarkers in obese people, while weight-loss dietary interventions might have beneficial effects in attenuating the associations.