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Epigenetic Aging Accelerated by Lifetime Stress

Cumulative exposure to stress hormones affects the regulation of genes associated with aging and age-related diseases.

An important risk factor for accelerated aging and age-related diseases is excessive or chronic stress. Scientists at the Max Planck Institute of Psychiatry in Munich have now found how psychological stress, which accumulates over a lifetime, accelerates the aging process. The reason for this are epigenetic changes at binding sites of the receptor for the stress molecule glucocorticoid.

One plausible mechanism that may mediate the adverse effects of stress on the aging process is epigenetic regulation. Epigenetic actions do not change the actual genetic code but alter its accessibility by i.e. attaching chemical groups to or removing them from the DNA. A team supervised by Elisabeth Binder, director at the Max Planck Institute of Psychiatry, investigated the effect of lifetime stress on a DNA methylation-based age predictor in blood samples from a cohort of highly traumatized African American individuals.

“Glucocorticoids are molecular effectors of our response to stress and can exert actions in essentially every body organ via activation of the stress-hormone receptor. The stress hormone receptor regulates gene expression by binding to specific response elements in the DNA. This can also lead to long lasting “epigenetic reprogramming,” explains Anthony Zannas, leading scientist in the current study. “ We found that such a stress-induced reprogramming happens in sites that are associated with aging.”

The study showed that individuals exposed to high levels of lifetime stress were epigenetically older than their true biological age. Such a premature “biological” aging has been shown to increase the risk for a number of age-related diseases. Exposure to stress may thus lead to more aging-related diseases by long-lasting epigenetic effects induced by the chronic activation of stress-hormone receptors.

Image shows a pink DNA double helixes.

The study showed that individuals exposed to high levels of lifetime stress were epigenetically older than their true biological age. Such a premature “biological” aging has been shown to increase the risk for a number of age-related diseases. Image is for illustrative purposes only.

Measuring the epigenetic age in peripheral blood cells may be a possibility to identify chronically stressed individuals at high risk for cardiovascular diseases or dementia and to initiate timely prevention programs.

About this stress and aging research

Source: Dr. Anthony Zannas – Max Planck Institute
Image Source: The image is in the public domain
Original Research: Full open access research for “Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling” by Zannas AS, Arloth J, Carrillo-Roa T, Iurato S, Röh S, Ressler KJ, Nemeroff CB, Smith AK, Bradley B, Heim C, Menke, Lange JF, Brückl T, Ising M, Wray NR, Erhardt A, Binder EB, and Mehta D. in Genome Biology. Published online December 21 2015 doi:10.1186/s13059-015-0828-5


Abstract

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

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.

“Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling” by Zannas AS, Arloth J, Carrillo-Roa T, Iurato S, Röh S, Ressler KJ, Nemeroff CB, Smith AK, Bradley B, Heim C, Menke, Lange JF, Brückl T, Ising M, Wray NR, Erhardt A, Binder EB, and Mehta D. in Genome Biology. Published online December 21 2015 doi:10.1186/s13059-015-0828-5

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