Association of lifestyle and cardiometabolic risk factors with epigenetic age acceleration in adults in China

Abstract

Objective: To explore the association of lifestyle and cardiometabolic risk factors with five epigenetic age acceleration (AA) indices. Methods: This study included 980 participants of China Kadoorie Biobank, for whom genome-wide DNA methylation of peripheral blood cells had been detected in baseline survey. Five indices of DNA methylation age (DNAm age) were calculated, i.e. Horvath clock, Hannum clock, DNAm PhenoAge, GrimAge and Li clock. Epigenetic AA was defined as the residual of regressing DNAm age on chronological age. Lifestyle factors studied included smoking status, alcohol consumption, eating habits, physical activity level and body shape defined by a combination of BMI and waist circumference. Cardiometabolic risk factors included blood pressure, blood glucose level and total cholesterol level. Linear regression model was used to analyze the association of lifestyle and cardiometabolic risk factors with AA (β). Results: GrimAge_AA was associated with smoking status, alcohol consumption, physical activity level and BMI. Compared with non-smokers, non-drinkers, or participants with BMI of 18.5- 23.9 kg/m2, the smokers who smoked 1-14 cigarettes/day (β=0.71, 95%CI: 0.57-0.86), 15-24 cigarettes/day (β=0.88, 95%CI: 0.73-1.03), and ≥25 cigarettes/day (β=0.99, 95%CI: 0.81-1.18), respectively, heavy drinkers with daily pure alcohol consumption ≥60 g (β=0.33, 95%CI: 0.11-0.55) and participants with BMI<18.5 kg/m2 (β=0.23, 95%CI: 0.03-0.43) showed accelerated aging. Compared with those in the lowest quintile of physical activity level, participants in the top three quintile of physical activity level showed decelerated aging (β=-0.13, 95%CI: -0.26-0.01, β=-0.12, 95%CI: -0.26-0.02, and β=-0.14, 95%CI: -0.27- -0.00, respectively). GrimAge_AA decreased with the increase of the number of healthy lifestyle factors (P<0.001). Compared with the participants with 0 to 1 healthy lifestyle factor, the β of those with 2, 3, or 4 to 5 healthy lifestyle factors were -0.30 (95%CI: -0.47- -0.12), -0.47 (95%CI: -0.65- -0.30) and -0.72 (95%CI: -0.90- -0.53), respectively. The other four indices were not statistically significantly associated with most lifestyle factors. None of the five indices of AA was associated with blood pressure, blood glucose level or total cholesterol level. Conclusion: People with unhealthy lifestyle showed accelerated epigenetic aging, that is, the predicted DNAm age is older than their own chronological age.