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Genome Biol. 2019 Nov 25;20(1):249. doi: 10.1186/s13059-019-1824-y.

DNA methylation aging clocks: challenges and recommendations.

Author information

1
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. c.bell@qmul.ac.uk.
2
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. rlowe.compbio@gmail.com.
3
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA. padams@sbpdiscovery.org.
4
Beatson Institute for Cancer Research and University of Glasgow, Glasgow, UK. padams@sbpdiscovery.org.
5
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. ab4303@cumc.columbia.edu.
6
Medical Genomics, Paul O'Gorman Building, UCL Cancer Institute, University College London, London, UK. s.beck@ucl.ac.uk.
7
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. jordana.bell@kcl.ac.uk.
8
Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. brock.christensen@dartmouth.edu.
9
Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. brock.christensen@dartmouth.edu.
10
Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA. brock.christensen@dartmouth.edu.
11
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. vgladyshev@rics.bwh.harvard.edu.
12
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. b.t.heijmans@lumc.nl.
13
Department of Human Genetics, Gonda Research Center, David Geffen School of Medicine, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
14
Department of Biostatistics, School of Public Health, University of California-Los Angeles, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
15
San Diego Center for Systems Biology, University of California-San Diego, San Diego, CA, USA. trey.ideker@gmail.com.
16
Fels Institute for Cancer Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. jpissa@temple.edu.
17
Department of Epidemiology, Brown University, Providence, RI, USA. karl_kelsey@brown.edu.
18
Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA. karl_kelsey@brown.edu.
19
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. riccardo.marioni@ed.ac.uk.
20
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. riccardo.marioni@ed.ac.uk.
21
Epigenetics Programme, The Babraham Institute, Cambridge, UK. wolf.reik@babraham.ac.uk.
22
The Wellcome Trust Sanger Institute, Cambridge, UK. wolf.reik@babraham.ac.uk.
23
Medical Research Council Integrative Epidemiology Unit (MRC IEU), School of Social and Community Medicine, University of Bristol, Bristol, UK. caroline.relton@bristol.ac.uk.
24
School of Biological Sciences, University of Essex, Colchester, UK. lschal@essex.ac.uk.
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. a.teschendorff@ucl.ac.uk.
26
UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London, WC1E 6BT, UK. a.teschendorff@ucl.ac.uk.
27
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen Faculty of Medicine, Aachen, Germany. wwagner@ukaachen.de.
28
Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau. kang.zhang@gmail.com.
29
The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. v.rakyan@qmul.ac.uk.

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.

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