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Research Paper|Volume 10, Issue 11|pp 3541—3557

Cell and tissue type independent age-associated DNA methylation changes are not rare but common

Tianyu Zhu1, Shijie C Zheng1, Dirk S. Paul2, Steve Horvath3,4, Andrew E. Teschendorff1,5
  • 1CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • 2Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK
  • 3Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
  • 4Department of Biostatistics, Fielding School of Public Healthy, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 5UCL Cancer Institute, Paul O’Gorman Building, University College London, London WC1E 6BT, UK
Received: September 21, 2018Accepted: November 15, 2018Published: November 27, 2018
https://doi.org/10.18632/aging.101666

Copyright: © 2018 Zhu 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

Age-associated DNA methylation changes have been widely reported across many different tissue and cell types. Epigenetic ‘clocks’ that can predict chronological age with a surprisingly high degree of accuracy appear to do so independently of tissue and cell-type, suggesting that a component of epigenetic drift is cell-type independent. However, the relative amount of age-associated DNAm changes that are specific to a cell or tissue type versus the amount that occurs independently of cell or tissue type is unclear and a matter of debate, with a recent study concluding that most epigenetic drift is tissue-specific. Here, we perform a novel comprehensive statistical analysis, including matched multi cell-type and multi-tissue DNA methylation profiles from the same individuals and adjusting for cell-type heterogeneity, demonstrating that a substantial amount of epigenetic drift, possibly over 70%, is shared between significant numbers of different tissue/cell types. We further show that ELOVL2 is not unique and that many other CpG sites, some mapping to genes in the Wnt and glutamate receptor signaling pathways, are altered with age across at least 10 different cell/tissue types. We propose that while most age-associated DNAm changes are shared between cell-types that the putative functional effect is likely to be tissue-specific.