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

Zannas, Anthony S., Arloth, Janine, Carrillo-Roa, Tania, Iurato, Stella, Roh, Simone, Ressler, Kerry J., Nemeroff, Charles B., Smith, Alicia K., Bradley, Bekh, Heim, Christine, Menke, Andreas, Lange, Jennifer F., Bruckl, Tanja, Ising, Marcus, Wray, Naomi R., Erhardt, Angelika, Binder, Elisabeth B. and Mehta, Divya (2015) Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. Genome Biology, 16 1: 1-12. doi:10.1186/s13059-015-0828-5


Author Zannas, Anthony S.
Arloth, Janine
Carrillo-Roa, Tania
Iurato, Stella
Roh, Simone
Ressler, Kerry J.
Nemeroff, Charles B.
Smith, Alicia K.
Bradley, Bekh
Heim, Christine
Menke, Andreas
Lange, Jennifer F.
Bruckl, Tanja
Ising, Marcus
Wray, Naomi R.
Erhardt, Angelika
Binder, Elisabeth B.
Mehta, Divya
Title Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
1474-7596
Publication date 2015-12-17
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s13059-015-0828-5
Open Access Status DOI
Volume 16
Issue 1
Start page 1
End page 12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted 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.
Keyword Aging
Aging-related disease
DNA methylation
Epigenetics
Gene expression
Glucocorticoids
Psychological stress
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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