Research Paper
Theobromine is associated with slower epigenetic ageing
- 1 Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas’ Hospital Campus, London SE1 7EH, UK
- 2 North East Thames Regional Genetic Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- 3 Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- 4 Department of Physiology and Biophysics, Weill Cornell Medicine - Qatar, Education City - Qatar Foundation, Doha, Qatar
- 5 Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- 6 Institute for Medical Informatics, Biometrics and Epidemiology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany
- 7 Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- 8 Department of Nutrition, King’s College London, St Thomas’ Hospital Campus, London SE1 7EH, UK
- 9 Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK
- 10 Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Via Francesco Sforza, Milan 20122, Italy
- 11 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan 20122, Italy
Received: April 22, 2025 Accepted: November 11, 2025
https://doi.org/10.18632/aging.How to Cite
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.
Abbreviations
CAF: Caffeine; DNAm: DNA methylation; MX: 7-methylxanthine; PX: Paraxanthine; TB: Theobromine; TP: Theophylline.