Chronic psychological stress is associated with accelerated ageing and increased risk for ageing-related diseases, but the underlying molecular mechanisms are unclear.
Scientists at the Max Planck Institute of Psychiatry in Munich have now found how psychological stress, which accumulates over a lifetime, accelerates the ageing process. The reason for this is epigenetic changes at the binding sites of the receptor for the stress molecule glucocorticoid.
The study showed that individuals exposed to high levels of lifetime stress were epigenetically older than their true biological age. Such premature “biological” ageing has increased the risk for several age-related diseases.
One plausible mechanism that may mediate the adverse effects of stress on the ageing process is epigenetic regulation.
Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. 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.
They examined the effect of lifetime stressors on a DNA methylation-based age predictor, the epigenetic clock. (see below for what that clock is)
Cumulative exposure to stress hormones affects the regulation of genes associated with aging and age-related diseases.
The study showed that individuals exposed to high levels of lifetime stress were epigenetically older than their true biological age. Such premature “biological” ageing has been shown to increase the risk for a number of age-related diseases.
http://www.genomebiology.com/2015/16/1/266#B27
While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterised.
The plasticity, tissue-specific nature, and gene expression variability are related to epigenomic states that vary across individuals.
Since age strongly affects DNA methylation levels on tens of thousands of CpG sites, one can define a highly accurate biological clock (referred to as epigenetic clock or DNA methylation age) in humans and chimpanzees.
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. "CpG" is shorthand for "—C—phosphate—G—", that is, cytosine and guanine separated by only one phosphate.
Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosine. In mammals, , 70% to 80% of CpG cytosines are methylated. Methylating the cytosine within a gene can change its expression,
CpG islands (or CG islands) are regions with a high frequency of CpG sites and they are what is used to provide researchers nowadays with an epigenetic clock.
Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context
http://journals.plos.org/plosgenetics/article…
“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.”
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.
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.
We found that GREs co-localize with epigenetic clock CpGs and that glucocorticoid activation can induce dynamic methylation changes of these sites as well as changes in the expression of genes neighboring epigenetic clock CpGs
No comments:
Post a Comment