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Lifetime Stress Accelerates Epigenetic Aging

Published online by Cambridge University Press:  15 April 2020

A. Zannas ,
T. Carrillo-Roa ,
S. Iurato ,
K. Ressler ,
C. Nemeroff ,
A. Smith ,
J. Lange ,
B. Bradley ,
C. Heim  and
T. Brückl
...Show all authors
A. Zannas
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
T. Carrillo-Roa
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
S. Iurato
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
K. Ressler
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, USA
C. Nemeroff
Affiliation:
Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, USA
A. Smith
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, USA
J. Lange
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
B. Bradley
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, USA
C. Heim
Affiliation:
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, USA
T. Brückl
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
M. Ising
Affiliation:
Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany
N. Wray
Affiliation:
Queensland Brain Institute, University of Queensland, Queensland, Australia
A. Erhardt
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
E. Binder
Affiliation:
Translational Research, Max Planck Institute of Psychiatry, Munich, Germany
D. Mehta
Affiliation:
Queensland Brain Institute, The University of Queensland, Queensland, Australia

Abstract

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Background

Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.

Methods

We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.

Results

DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10<sup>-133</sup>). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.

Conclusions

Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.

Type
Article: 0799
Information
European Psychiatry , Volume 30 , Issue S1: Abstracts of the 23rd European Congress of Psychiatry , March 2015 , pp. 1
Copyright
Copyright © European Psychiatric Association 2015
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