Abstract
BackgroundDNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (∆mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets.ResultsAmong 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean ± SD: 60.3 ± 7.5 years) was higher than the chronological age (48.6 ± 9.3 years) but strongly correlated (r = 0.93; p = 3.1 × 10–53). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p < 0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (β = 0.23; p = 0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r = 0.94, p = 1.5 × 10–55). mAging occurred, with no difference between lifestyle intervention groups (∆ = 0.9 ± 1.9 years in MED/LC vs. ∆ = 1.3 ± 1.9 years in LF; p = 0.2); however, we observed a mAging attenuation in successful weight losers (> 5% weight loss) vs. weight-loss failures ( ∆ = 0.6 years vs. ∆ = 1.1 years; p = 0.04), and in participants who completed the trial with healthy liver fat content (< 5% IHF) vs. participants with fatty liver (∆ = 0.6 years vs. ∆ = 1.8 years; p = 0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p < 0.05).ConclusionsLifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases.Trial registration: ClinicalTrials.gov NCT01530724. Registered 10 February 2012, https://clinicaltrials.gov/ct2/show/study/NCT01530724.
Highlights
DNA methylation age, a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age
Deviation of methylation age (mAge) from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases
Prediction of age by methylation level at specific sites has been performed among several populations, by different prediction formulas, described as “epigenetic clock,” “age acceleration” or “methylation age”
Summary
DNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. Prediction of age by methylation level at specific sites has been performed among several populations (which differed mainly by age and/or race), by different prediction formulas, described as “epigenetic clock,” “age acceleration” (expressing the difference between age predicted by DNA methylation and chronological age) or “methylation age” (mAge). Methylation aging, the deviation between mAge and chronological age, or age acceleration, are suggested to be strong predictors of all-cause mortality [12, 14] and fatal and nonfatal cardiovascular disease [15,16,17,18] In another epigenetic clock study, using Horvath’s 353 CpG-based formula, epigenetic aging rates were significantly associated with sex, race/ethnicity and coronary heart disease risk factors [19]. In another epigenetic clock study, using Horvath’s 353 CpG-based formula, epigenetic aging rates were significantly associated with sex, race/ethnicity and coronary heart disease risk factors [19]. mAge was higher with greater air pollution [11] and body mass index (BMI)[20]
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