Abstract
The understanding of mechanisms linking psychological stress to disease risk depend on reliable stress biomarkers. Circulating cell-free DNA (cfDNA) has emerged as a potential biomarker of cellular stress, aging, inflammatory processes, and cell death. Recent studies indicated that psychosocial stress and physical exercise might also influence its release. We compared the effects of acute psychosocial and physical exercise stress on cfDNA release by exposing 20 young, healthy men to both an acute psychosocial laboratory stressor and an acute physical exercise stressor. Venous blood and saliva samples were collected before and after stress exposure. Cell-free DNA was extracted from plasma and quantified by qPCR. Furthermore, cfDNA fragment length was analyzed and cfDNA methylation patterns were assayed across time. In addition, release of stress hormones and subjective stress responses were measured. Results showed a twofold increase of cfDNA after TSST and fivefold increase after exhaustive treadmill exercise, with an overabundance of shorter cfDNA fragments after physical exhaustion. Interestingly, cell-free mitochondrial DNA showed similar increase after both stress paradigms. Furthermore, cfDNA methylation signatures—used here as a marker for diverse cellular origin—were significantly different post stress tests. While DNA methylation decreased immediately after psychosocial stress, it increased after physical stress, suggesting different cellular sources of active DNA release. In summary, our results suggest stimulus and cell-specific regulation of cfDNA release. Whereas the functional role of stress-associated cfDNA release remains elusive, it might serve as a valuable biomarker in molecular stress research as a part of the psychophysiological stress response.
Highlights
Increased levels of circulating cell-free DNA in the bloodstream, either of genomic or mitochondrial origin, are hallmark manifestations of acute systemic inflammatory responses as well as of chronic inflammation
CfDNA rapidly decreased after reaching peak levels and returned close to baseline levels cell-free DNA (cfDNA)
The understanding of the mechanisms linking psychosocial stress to disease risk depend on reliable stress biomarkers
Summary
Increased levels of circulating cell-free DNA (cfDNA) in the bloodstream, either of genomic or mitochondrial origin, are hallmark manifestations of acute systemic inflammatory responses as well as of chronic inflammation. Elevated levels have been reported after trauma, sepsis, stroke, ischemia/reperfusion injury, or myocardial infarction, and in patients suffering from cancer, autoimmune and cardiovascular diseases, as well as metabolic disorders[1,2,3,4]. Altered levels of circulating cell-free mitochondrial DNA (cfmtDNA) in the plasma of suicide attempters and in major depressive disorder have been described[16,17,18]. Increased plasma cf-mtDNA levels in suicide attempters were significantly and positively correlated with cortisol levels after dexamethasone suppression, an indicator of hyperactivity of the HPA axis, the organism’s major hormonal stress response system[17]
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