Research Paper Volume 10, Issue 7 pp 1758—1775
Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies
- 1 Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- 2 Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
- 3 Department of Pathology, University of Washington, Seattle, WA 98195, USA
- 4 Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
- 5 Elizabeth House, Warlingham, Surrey CR6 9LF, United Kingdom
- 6 Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, United Kingdom
- 7 Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
- 8 Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, United Kingdom
- 9 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA
- 10 Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- 11 Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
- 12 Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA
- 13 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
- 14 Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA
- 15 Departments of Genetics, Biostatistics, Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA
- 16 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
- 17 Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27516, USA
- 18 Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 19 Department of Pathology and Pharmacology, Case Comprehensive Centre, Case Western Reserve University, Cleveland, OH 44106, USA
Received: May 27, 2018 Accepted: July 21, 2018 Published: July 26, 2018
https://doi.org/10.18632/aging.101508How to Cite
Copyright: Horvath et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay.