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

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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Zannas AS,Arloth J,Carrillo-Roa T,Iurato S,Röh S,Ressler KJ,Nemeroff CB,Smith AK,Bradley B,Heim C,Menke A,Lange JF,Brückl T,Ising M,Wray NR,Erhardt A,Binder EB,Mehta D

doi

10.1186/s13059-015-0828-5

subject

Has Abstract

pub_date

2015-12-17 00:00:00

pages

266

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-015-0828-5

journal_volume

pub_type

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