DNA methylation aging clocks: challenges and recommendations

  • Genome Biol. 2019 Nov 25;20(1):249. doi: 10.1186/s13059-019-1824-y.
Christopher G Bell  1 ,  Robert Lowe  2 ,  Peter D Adams  3  4 ,  Andrea A Baccarelli  5 ,  Stephan Beck  6 ,  Jordana T Bell  7 ,  Brock C Christensen  8  9  10 ,  Vadim N Gladyshev  11 ,  Bastiaan T Heijmans  12 ,  Steve Horvath  13  14 ,  Trey Ideker  15 ,  Jean-Pierre J Issa  16 ,  Karl T Kelsey  17  18 ,  Riccardo E Marioni  19  20 ,  Wolf Reik  21  22 ,  Caroline L Relton  23 ,  Leonard C Schalkwyk  24 ,  Andrew E Teschendorff  25  26 ,  Wolfgang Wagner  27 ,  Kang Zhang  28 ,  Vardhman K Rakyan  29
Affiliations
  • 1. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [email protected].
  • 2. The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [email protected].
  • 3. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. [email protected].
  • 4. Beatson Institute for Cancer Research and University of Glasgow, Glasgow, UK. [email protected].
  • 5. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. [email protected].
  • 6. Medical Genomics, Paul O'Gorman Building, UCL Cancer Institute, University College London, London, UK. [email protected].
  • 7. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. [email protected].
  • 8. Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. [email protected].
  • 9. Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. [email protected].
  • 10. Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. [email protected].
  • 11. Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. [email protected].
  • 12. Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. [email protected].
  • 13. Department of Human Genetics, Gonda Research Center, David Geffen School of Medicine, Los Angeles, CA, USA. [email protected].
  • 14. Department of Biostatistics, School of Public Health, University of California-Los Angeles, Los Angeles, CA, USA. [email protected].
  • 15. San Diego Center for Systems Biology, University of California-San Diego, San Diego, CA, USA. [email protected].
  • 16. Fels Institute for Cancer Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. [email protected].
  • 17. Department of Epidemiology, Brown University, Providence, RI, USA. [email protected].
  • 18. Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. [email protected].
  • 19. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. [email protected].
  • 20. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. [email protected].
  • 21. Epigenetics Programme, The Babraham Institute, Cambridge, UK. [email protected].
  • 22. The Wellcome Trust Sanger Institute, Cambridge, UK. [email protected].
  • 23. Medical Research Council Integrative Epidemiology Unit (MRC IEU), School of Social and Community Medicine, University of Bristol, Bristol, UK. [email protected].
  • 24. School of Biological Sciences, University of Essex, Colchester, UK. [email protected].
  • 25. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, 200031, China. [email protected].
  • 26. UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London, WC1E 6BT, UK. [email protected].
  • 27. Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen Faculty of Medicine, Aachen, Germany. [email protected].
  • 28. Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau. [email protected].
  • 29. The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. [email protected].
PMID: 31767039 DOI: 10.1186/s13059-019-1824-y
Abstract

Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions. Here, we discuss key challenges to understand clock mechanisms and biomarker utility. This requires dissecting the drivers and regulators of age-related changes in single-cell, tissue- and disease-specific models, as well as exploring other epigenomic marks, longitudinal and diverse population studies, and non-human models. We also highlight important ethical issues in forensic age determination and predicting the trajectory of biological aging in an individual.