Research Paper Volume 11, Issue 16 pp 5895—5923
DNA methylation-based estimator of telomere length
- 1 Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- 2 Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
- 3 Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK
- 4 Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
- 5 Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- 6 Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
- 7 Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA
- 8 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- 9 Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 10 Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
- 11 Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA
- 12 Departments of Genetics, Biostatistics, Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA
- 13 Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK
- 14 Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK
- 15 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
- 16 Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
- 17 VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
- 18 Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
- 19 Children’s Minnesota Research Institute, Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA
- 20 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA
- 21 Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA
- 22 Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, UK
- 23 Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
Received: July 25, 2019 Accepted: August 5, 2019 Published: August 18, 2019
https://doi.org/10.18632/aging.102173How to Cite
Copyright © 2019 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly associated with age than measured leukocyte TL (LTL) (r ~-0.75 for DNAmTL versus r ~ -0.35 for LTL). Leukocyte DNAmTL outperforms LTL in predicting: i) time-to-death (p=2.5E-20), ii) time-to-coronary heart disease (p=6.6E-5), iii) time-to-congestive heart failure (p=3.5E-6), and iv) association with smoking history (p=1.21E-17). These associations are further validated in large scale methylation data (n=10k samples) from the Framingham Heart Study, Women's Health Initiative, Jackson Heart Study, InChianti, Lothian Birth Cohorts, Twins UK, and Bogalusa Heart Study. Leukocyte DNAmTL is also associated with measures of physical fitness/functioning (p=0.029), age-at-menopause (p=0.039), dietary variables (omega 3, fish, vegetable intake), educational attainment (p=3.3E-8) and income (p=3.1E-5). Experiments in cultured somatic cells show that DNAmTL dynamics reflect in part cell replication rather than TL per se. DNAmTL is not only an epigenetic biomarker of replicative history of cells, but a useful marker of age-related pathologies that are associated with it.