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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-149865
  • 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). ThisBackground 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.show moreshow less

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Metadaten
Author: Anthony S. Zannas, Janine Arloth, Tania Carrillo-Roa, Stella Iurato, Simone Röh, Kerry J. Ressler, Charles B. Nemeroff, Alicia K. Smith, Bekh Bradley, Christine Heim, Andreas Menke, Jennifer F. Lange, Tanja Brückl, Marcus Ising, Naomi R. Wray, Angelika Erhardt, Elisabeth B. Binder, Divya Mehta
URN:urn:nbn:de:bvb:20-opus-149865
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):Genome Biology
Year of Completion:2015
Volume:16
Issue:266
Source:Genome Biology (2015) 16:266. DOI: 10.1186/s13059-015-0828-5
DOI:https://doi.org/10.1186/s13059-015-0828-5
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/PMC4699359
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:DNA methylation; aging; aging-related disease; epigenetics; gene expression; glucocorticoids; psychological stress
Release Date:2019/01/23
EU-Project number / Contract (GA) number:281338
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International