Molecular effects of insufficient sleep uncovered

By Eleanor McDermid, Senior medwireNews Reporter

Results from a sleep laboratory study show striking changes in gene expression associated with sleep deprivation.

Although the magnitude of change in expression was "relatively small," a large number of genes were affected, report Derk-Jan Dijk (University of Surrey, Guildford, UK) and team - 711 genes in the study participants' blood were upregulated or downregulated after a week of insufficient sleep.

Furthermore, many of these genes were involved in important health-related processes, including the inflammatory, immune, and stress responses, show the findings in the Proceedings of the National Academy of Sciences of the United States of America.

The 26 participants (14 men and 12 women, average age 27.5 years) had an average of 5.7 hours sleep for 7 consecutive nights, causing them to become significantly more sleepy and have more attention lapses during the Psychomotor Vigilance Task than after a control sleep period, during which they averaged 8.5 hours' sleep per night.

The 711 affected genes represented about 3% of those present in the participants' blood samples. In all, 267 genes were upregulated and 444 were downregulated by sleep restriction; many of these were involved in circadian rhythms and sleep. In all, 1855 genes showed circadian variation in expression during control sleep conditions. Sleep restriction reduced the number to 1481, but this included 688 genes that were only circadian under these conditions.

"Circadian organization of the transcriptome and physiology are often implicated in health and disease," say Dijk et al. "Our data show that this circadian organization is altered and this could be one general pathway by which sleep restriction leads to health problems."

The biologic processes with the largest proportion of downregulated genes after sleep restriction were cellular and macrometabolic processes. There was less upregulation than downregulation of genes, but the processes most affected were the cellular response to oxidative stress and to reactive oxygen species and the stress response. "Our data suggest several pathways by which sleep restriction and circadian rhythmicity may be linked to negative health outcomes associated with insufficient sleep," observe the researchers.

After the control and restricted sleep periods, the study participants undertook a period of about 40 hours of sleep deprivation. Expression of 0.5% of all genes was influenced by the total time spent awake after control sleep conditions, but this increased to 3.8% after a week of sleep deprivation.

"The intensified response to acute sleep deprivation following sleep restriction may imply that insufficient sleep increases the response to challenges and stressors, and in this way negatively affects health," suggest the researchers.

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