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Research Paper|Volume 9, Issue 9|pp 1983—1995

Leukocyte telomere length, T cell composition and DNA methylation age

Brian H. Chen1,2,3, Cara L. Carty4, Masayuki Kimura5, Jeremy D. Kark6, Wei Chen7, Shengxu Li7, Tao Zhang7, Charles Kooperberg8, Daniel Levy2,3, Themistocles Assimes9, Devin Absher10, Steve Horvath11,12, Alexander P. Reiner8,13, Abraham Aviv5
  • 1Longitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 2Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA
  • 3Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
  • 4Division of Biostatistics and Study Methodology, Center for Translational Science, George Washington University and Children's National Medical Center, Washington, DC 20010, USA
  • 5Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA
  • 6Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel
  • 7Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70118, USA
  • 8Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
  • 9Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
  • 10HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA
  • 11Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 12Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 13Department of Epidemiology, University of Washington, Seattle, WA 98195, USA

* * Equal contribution

Received: July 17, 2017Accepted: September 17, 2017Published: September 20, 2017

Copyright: © 2017 Chen 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

Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age─ the extrinsic epigenetic age acceleration (EEAA)─ is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826). EEAA was computed using 71 DNA methylation sites, further weighted by proportions of naïve CD8+ T cells, memory CD8+ T cells, and plasmablasts. Shorter LTL was associated with increased EEAA in participants from the WHI (r=-0.16, p=3.1x10-6). This finding was replicated in the FHS (r=-0.09, p=6.5x10-3) and the BHS (r=-0.07, p=3.8x 10-2). LTL was also inversely related to proportions of memory CD8+ T cells (p=4.04x10-16) and positively related to proportions of naive CD8+ T cells (p=3.57x10-14). These findings suggest that for a given age, an individual whose blood contains comparatively more memory CD8+ T cells and less naive CD8+ T cells would display a relatively shorter LTL and an older DNA methylation age, which jointly explain the striking ability of EEAA to predict mortality.

Leukocyte telomere length, T cell composition and DNA methylation age | Aging