Abstract
Abstract
Background
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. 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.
Results
Among 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).
Conclusions
Lifestyle 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.
Funder
Deutsches Zentrum für Herz-Kreislaufforschung
Deutsche Forschungsgemeinschaft
the German Diabetes Association
the Israel Science Foundation
Israel Ministry of Science and Technology
Dr. Robert C. and Veronica Atkins Foundation
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Developmental Biology,Genetics,Molecular Biology
Reference47 articles.
1. McKay JA, Mathers JC. Diet induced epigenetic changes and their implications for health. Acta Physiol. 2011;202:103–18.
2. van Eijk KR, de Jong S, Boks MPM, Langeveld T, Colas F, Veldink JH, et al. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects. BMC Genomics. 2012;13:636.
3. Tammen SA, Friso S, Choi S-W. Epigenetics: the link between nature and nurture. Mol Aspects Med. 2013;34:753–64.
4. Arpon A, Riezu-Boj JI, Milagro FI, Razquin C, Martínez-González MA, Corella D, et al. Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells. J Physiol Biochem. 2017;10:1–11.
5. Voisin S, Eynon N, Yan X, Bishop DJ. Exercise training and DNA methylation in humans. Acta Physiol. 2015;213:39–59.