Research Paper|Volume 9, Issue 4|pp 1143—1152

Accelerated epigenetic aging in Werner syndrome

Anna Maierhofer¹, Julia Flunkert¹, Junko Oshima^2,³, George M. Martin², Thomas Haaf^1,⁶, Steve Horvath^4,^5,⁶

¹Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
²Department of Pathology, University of Washington, Seattle, WA 98105, USA
³Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
⁴Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
⁵Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
⁶Joint last authors

Received: February 21, 2016Accepted: March 23, 2017Published: April 4, 2017

Copyright: © 2017 Maierhofer 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

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.