Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial

  • Anat Yaskolka Meir (Creator)
  • Maria Keller (Creator)
  • Stephan H. Bernhart (Creator)
  • Ehud Rinott (Creator)
  • Gal Tsaban (Creator)
  • Hila Zelicha (Creator)
  • Alon Kaplan (Creator)
  • Dan Schwarzfuchs (Creator)
  • Ilan Shelef (Creator)
  • Yftach Gepner (Creator)
  • Jun Li (Creator)
  • Yifei Lin (Creator)
  • Matthias Blüher (Creator)
  • Uta Ceglarek (Creator)
  • Michael Stumvoll (Creator)
  • Peter F. Stadler (Creator)
  • Meir J. Stampfer (Creator)
  • Peter Kovacs (Creator)
  • Liming Liang (Creator)
  • Iris Shai (Creator)



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  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 (
Date made available2021

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