11 May 2018

You need to sleep at night

Gene expression could not adjust to the night shift

Elizaveta Ivtushok, N+1

Gene expression regulated by circadian rhythms does not adjust to the daily routine when working the night shift, according to an article published in the journal Proceedings of the National Academy of Sciences. Canadian scientists found out this by analyzing the transcriptome of people who went to bed ten hours later than usual for four days. 

In humans, circadian rhythms are tuned to a 24-hour cycle and are regulated by light: it is the chain of proteins and genes responsible for sleep and wakefulness cycles that make us want to sleep at night (through the production of melatonin) and get up in the morning (cortisol production is largely responsible for this). The biological clock of modern man is often confused: this is not only the fault of ubiquitous artificial lighting, but also the need, for example, to work at night and make long flights.

The transition to a nocturnal lifestyle is associated with the appearance of numerous health problems, both physical and mental: among the possible consequences are sleep and eating disorders, obesity, cardiovascular diseases and depression. One sleepless night, for example, in terms of negative effects on the body is equal to half a year of fast food abuse, and also significantly increases the amount of beta-amyloids in the brain – pathological forms of proteins responsible, among other things, for the development of Alzheimer's disease. 

The molecular basis of the physiological effects of changing circadian rhythms, however, has not yet been fully studied. Biologists from McGill University (Montreal, Canada), led by Laura Kervezee, decided to test how a sleepless night affects genes whose expression is tuned by the biological clock of the body. Eight volunteers took part in their experiment (the average age was 22.5 years), who were placed in laboratory rooms for several days. A peripheral blood sample was taken from each of them several times a day (from 12 to 14 times in total for the entire period), from which RNA was isolated for genome–wide analysis. 

The participants were allowed to spend the first day of the study the way they usually spend it: this allowed the scientists to consider the "habitual" gene expression for each volunteer, as well as to find out the time of normal bedtime. Over the next four days, the participants were placed on a simulation of working the night shift, allowing them to go to bed only ten hours after normal time. Participants were also allowed to sleep only eight hours a day.

When switching to night shift work, participants on average slept less: on the last day of the study – about 38 minutes less than the time allowed to them. After analyzing the transcriptome of the participants, the scientists identified genes whose increased or decreased expression depends on the work of the individual biological clocks of the participants. In addition to the genes regulating circadian rhythms (for example, CLOCK), scientists also noted, for example, FCGR3A and GNLY involved in maintaining immunity (they participate in the production of antibodies), as well as MPI involved in the metabolism process (it is responsible for carbohydrate metabolism).

Scientists found that 73 percent of all isolated genes were unable to adapt to the regime change. Their expression remained "tuned" to the usual daily routine: despite the changed circumstances, the participants' organism existed in accordance with the usual sleep and wakefulness cycles.

The authors note that the experiment took place under strictly controlled laboratory conditions, so the environmental validity of the results obtained is quite low, and in the future it is necessary to conduct research with the participation of people working the night shift in real life. It is also worth noting that the small sample of the study is explained by the high cost of transcriptome analysis studies. 

Often, people do not just knock down their natural biological clocks one sleepless night, but systematically disrupt their work, preferring a nocturnal lifestyle. It is not yet known exactly how well the body of the "owls" is adjusted to their chronotype, but recently scientists have found out that the evening-night regime is associated with an increased risk of early death from various causes.

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