TY  - JOUR
A1  - Zannas, Anthony S.
A1  - Arloth, Janine
A1  - Carrillo-Roa, Tania
A1  - Iurato, Stella
A1  - Röh, Simone
A1  - Ressler, Kerry J.
A1  - Nemeroff, Charles B.
A1  - Smith, Alicia K.
A1  - Bradley, Bekh
A1  - Heim, Christine
A1  - Menke, Andreas
A1  - Lange, Jennifer F.
A1  - Brückl, Tanja
A1  - Ising, Marcus
A1  - Wray, Naomi R.
A1  - Erhardt, Angelika
A1  - Binder, Elisabeth B.
A1  - Mehta, Divya
T1  - Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling
T2  - Genome Biology
N2  - 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.
KW  - aging
KW  - DNA methylation
KW  - gene expression
KW  - glucocorticoids
KW  - psychological stress
KW  - aging-related disease
KW  - epigenetics
Y1  - 2015
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/14986
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-149865
VL  - 16
IS  - 266
ER  -