Lack of sleep: All about genes and yawns

21. January 2014
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Anybody who frequently sleeps fewer than seven hours per night is weakening his or her immune system. Scientists in Helsinki have for the first time been able to show which biological mechanisms associated with sleep deprivation have an affect on the immune system.

Sleep deprivation has a direct impact on the human immune system. This is something well known. In a recent study published in the journal PLOS ONE, scientists at the University of Helsinki have now discovered important biological relationships between sleep reduction and the defence mechanisms of the body.

Sleep deprivation and inflammatory responses

Epidemiological studies in which the subjects involved gave information about their sleep patterns led researchers already some time ago to assume that too little sleep raises the risk of cardiovascular disease and type 2 diabetes. Whoever constantly sleeps less than seven hours a night also has an increased mortality risk – according to the available data. Many of the diseases that are associated with lack of sleep are associated with inflammatory responses in the body. Scientists in Helsinki have for the first time been able to show which biological mechanisms associated with sleep deprivation have an affect on the immune system. They were able to make genes identifiable which are also involved in the regulation of the immune system and whose transcription behaviour changes with sleep deprivation.

Only four hours of sleep per night for five days

In order to simulate a working week, nine healthy young men at the laboratories of the Finnish Institute for Occupational Safety were for five days permitted to sleep for only four hours a night. Before and after the sleep deprivation test, blood was taken from the subjects. The scientists isolated white blood cells from them and examined the gene expression in their study participants using microarrays. The results were compared by the researchers with data from four healthy men of similar age who were allowed eight hours of sleep a night during the same period. “We compared the gene expression before and after sleep deprivation and took a close look at the genes whose transcription frequency most varied”, explains Vilma Aho, a participating scientist.

Sleep deprivation altered gene expression

Sleep deprivation altered the frequency of transcription activity for a total of 117 genes. Eight of the 25 most up-regulated gene transcripts were directly linked to the immune system. In the metabolic pathways affected, the researchers met with a similar result: 15 of the 25 most accelerated metabolic pathways were associated with immunological functions. These included, for example, B-cell activation, interleukin8 production and the NF-κB signal pathway. “Under a state of sleep deprivation, for example, the activity of B-cells – also involved in allergic reactions and asthma – increased. This could explain the link between lack of sleep and increased asthmatic reactions”, says Aho. In addition to specific interleukins or signalling molecules that are involved in inflammation, the number of receptors, such as toll-like receptors, increased significantly when the subjects slept too little. At the genetic level this made itself more noticeable, in that the TLR4 gene was transcribed much more often during sleep deprivation periods than during normal sleep patterns. The concentrations of C-reactive protein (CRP) were also increased, indicating inflammation.

Effects of long-term sleep deprivation

Since the laboratory conditions resemble those of only few people in the real world, the scientists were also interested in investigating the effects of poor sleep on the immune system under real conditions. For this follow-up study, they referred to samples held by the national FINRISKI Health Survey. The 472 participants in this cohort study had already undergone blood tests and answered questions about their state of health and their sleep behaviour. The scientists compared the data derived from good sleepers with that of bad sleepers. Some changes in the transcription of certain genes were also confirmed by the scientists in this study population. The striking match between laboratory test and cohort study related to gene transcripts from genes with the names TBX21 and TGFBR3, both mediators of the immune system. LGR6 and STX16, which have been repeatedly associated with cancers, were also altered by lack of sleep in their transcription frequency. These four genes could play an important role in how lack of sleep affects the immune system, scientists suspect.

Aho summarises: “These results confirm the assumption that sleep apparently does not just affect our brain functions, but is also associated with our immune system and our metabolism. Sleep deprivation causes changes in the system which our immune system regulates. Some of these changes seem to have long-term consequences and may contribute to the development of diseases which have already been thus linked in epidemiological studies done on sleep deprivation”.

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