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Research Paper|Volume 17, Issue 12|pp 2902—2915

Theobromine is associated with slower epigenetic ageing

Ramy Saad1,2, Ricardo Costeira1, Pamela R. Matías-García3, Sergio Villicaña1, Christian Gieger3, Karsten Suhre4, Annette Peters5,6, Gabi Kastenmüller7, Ana Rodriguez-Mateos8, Cristina Dias9, Cristina Menni1,10,11, Melanie Waldenberger3, Jordana T. Bell1
  • 1Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas’ Hospital Campus, London SE1 7EH, UK
  • 2North East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  • 3Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 4Department of Physiology and Biophysics, Weill Cornell Medicine - Qatar, Education City - Qatar Foundation, Doha, Qatar
  • 5Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 6Institute for Medical Informatics, Biometrics and Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
  • 7Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • 8Department of Nutrition, King’s College London, St Thomas’ Hospital Campus, London SE1 7EH, UK
  • 9Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK
  • 10Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Via Francesco Sforza, Milan 20122, Italy
  • 11Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan 20122, Italy
Received: April 22, 2025Accepted: November 11, 2025Published: December 10, 2025
https://doi.org/10.18632/aging.206344

Copyright: © 2025 Saad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Theobromine, a commonly consumed dietary alkaloid derived from cocoa, has been linked to extended lifespan in model organisms and to health benefits in humans. We examined associations between circulating levels of theobromine intake, measured using serum metabolomics, and blood-based epigenetic markers of biological ageing in two European human population-based cohorts. Serum theobromine levels were significantly associated with reduced epigenetic age acceleration, as measured by GrimAge (p < 2e-7) and DNAmTL (p < 0.001) in 509 individuals from the TwinsUK cohort, and both signals replicated in 1,160 individuals from the KORA cohort (p = 7.2e-08 and p = 0.007, respectively). Sensitivity analyses including covariates of other cocoa and coffee metabolites suggest that the effect is specific to theobromine. Our findings indicate that the reported beneficial links between theobromine intake on health and ageing extend to the molecular epigenetic level in humans.