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Genome Biol. 2015 Dec 17;16:266. doi: 10.1186/s13059-015-0828-5.

Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling.

Author information

1
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. anthony_zannas@psych.mpg.de.
2
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. anthony_zannas@psych.mpg.de.
3
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
4
Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
5
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA, USA.
6
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
7
Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
8
Department of Psychiatry and Behavioral Sciences and the Center on Aging, University of Miami Miller School of Medicine, Miami, FL, USA.
9
Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
10
Institute of Medical Psychology, Charité Universitätsmedizin Berlin, Berlin, Germany.
11
Department of Biobehavioral Health, Pennsylvania State University, University Park, PA, USA.
12
Current Address: Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
13
Max Planck Institute of Psychiatry, Munich, Germany.
14
The University of Queensland, Queensland Brain Institute, St Lucia, Qld 4072, Australia.
15
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. binder@psych.mpg.de.
16
Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA, USA. binder@psych.mpg.de.

Abstract

BACKGROUND:

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

RESULTS:

We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias.

CONCLUSIONS:

Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.

PMID:
26673150
PMCID:
PMC4699359
DOI:
10.1186/s13059-015-0828-5
[Indexed for MEDLINE]
Free PMC Article

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