Research Paper Volume 9, Issue 9 pp 1983—1995
Leukocyte telomere length, T cell composition and DNA methylation age
- 1 Longitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 2 Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA
- 3 Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
- 4 Division of Biostatistics and Study Methodology, Center for Translational Science, George Washington University and Children's National Medical Center, Washington, DC 20010, USA
- 5 Center of Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA
- 6 Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel
- 7 Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70118, USA
- 8 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
- 9 Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
- 10 HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA
- 11 Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
- 12 Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
- 13 Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
Received: July 17, 2017 Accepted: September 17, 2017 Published: September 20, 2017
https://doi.org/10.18632/aging.101293How to Cite
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.