Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status

Abstract

Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p’s < 0.01). Parallel to the well-recognized fact that sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

Effects of a 36-h Survival Training with Sleep Deprivation on Oxidative Stress and Muscle Damage Biomarkers in Young Healthy Men

“…Free radicals are postulated to accumulate during awakening, inter alia, due to enhanced metabolic activity, and are claimed to be responsible for the unfavorable effects of sleep deprivation [ 32 , 33 ]. During sleep deprivation, the ability to perform tasks that require additional energy expenditure may be impaired [ 3 ].…”

Concise Review: Regulatory Influence of Sleep and Epigenetics on Adult Hippocampal Neurogenesis and Cognitive and Emotional Function

“…One route by which sleep deprivation could impact adult DG neurogenesis and thereby affect hippocampal function is through epigenetic modifications. Both acute and chronic sleep deprivation produce broad changes in epigenetic markers and patterns of gene transcription in rodents and humans . Of particular interest, depriving mice of sleep for 3 days downregulates hippocampal CBP expression, reduces hippocampal histone acetylation levels at Bdnf promoter regions, and weakens spatial memory , suggesting that sleep deprivation can impair cognition by disrupting hippocampal BDNF signaling, which is important for the maturation and growth of adult‐born DG neurons .…”

Neuroprotection, Photoperiod, and Sleep

“…However, some studies show effects of TSD that could not be considered as neuroprotective; for example, Trivedi et al [116] found that glutathione, ATP, cysteine, and homocysteine levels in plasma were significantly reduced as a result of one night of TSD, while Meier-Ewert et al [117] reported that one night of TSD increased serum C reactive protein concentrations. Also, one night of TSD causes an increase of serum concentration of interleukin 6 (IL-6), a proinflammatory cytokine in depressive patients as in healthy subjects; but in healthy individuals sleep rebound increased the level of interleukin-1-receptor antagonist (IL-1RA) [118], which inhibits the action of the proinflammatory interleukins 1alpha and 1beta.…”