Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies

DOI DOI Web Site 15 Citations 46 References Open Access
  • Steve Horvath
    Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • Junko Oshima
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
  • George M. Martin
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
  • Ake T. Lu
    Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • Austin Quach
    Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • Howard Cohen
    Elizabeth House, Warlingham, Surrey CR6 9LF, United Kingdom
  • Sarah Felton
    Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, United Kingdom
  • Mieko Matsuyama
    Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
  • Donna Lowe
    Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, United Kingdom
  • Sylwia Kabacik
    Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, United Kingdom
  • James G. Wilson
    Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA
  • Alex P. Reiner
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
  • Anna Maierhofer
    Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
  • Julia Flunkert
    Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
  • Abraham Aviv
    Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA
  • Lifang Hou
    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
  • Andrea A. Baccarelli
    Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA
  • Yun Li
    Departments of Genetics, Biostatistics, Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA
  • James D. Stewart
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
  • Eric A. Whitsel
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
  • Luigi Ferrucci
    Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • Shigemi Matsuyama
    Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
  • Kenneth Raj
    Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, United Kingdom

Description

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.

Journal

  • Aging

    Aging 10 (7), 1758-1775, 2018-07-26

    Impact Journals, LLC

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