Genetic effects of shift work examined
“Night work ‘throws body into chaos’,” reports the BBC News website.
The news is based on a new study from researchers at the University of Surrey which found that the daily rhythms of genes are disrupted by shifting sleep times.
In this new study, 22 participants were exposed to a 28-hour day without a natural light-dark cycle.
As a result, their sleep-wake cycle was delayed by four hours each day, until sleep occurred 12 hours out of sync with their “brain clock” and in the middle of what would have been their normal daytime.
Researchers then collected blood samples to measure the participants’ rhythms of gene expression (when RNA is made from “active” genes to make proteins and other products within the cell).
During this disruption of sleep timing, there was a six-fold reduction in the number of genes that displayed a circadian rhythm (a rhythm with an approximately 24 hour period).
One of the researchers described this as being akin to living in a house where every room had a clock set to a different time, “lead(ing) to chaos”.
Unfortunately this study was not available at the time of writing this story (see box for latest on study details). However, the “chaos” described is likely to refer to the molecular and should not cause readers too many further sleepless nights.
However, previous research by the same research group gives insights and clues to the results reported in today’s media.
Where did the story come from?
Both today’s study and the previous research were carried out by researchers from the University of Surrey and were funded by grants from the Biotechnology and Biological Sciences Research Council. The previous study was also funded by a grant from the Air Force Office of Scientific Research. The studies are to be published in the peer-reviewed journal PNAS.
PNAS is an open access journal, so all its content is free to read online or download. Unfortunately, at the time of writing the most recent study was not available from PNAS.
However, it is clear that some of the headlines were slightly over-the-top in reporting bodily “chaos” based on a small study that did not look at the test subjects’ health outcomes. In addition, the Daily Mail describes shift work as “damaging the genes”, when in fact the study found that it was the activity of genes that was changed.
What kind of research was this?
The previous study was a cross-over trial. It aimed to investigate the effects of a week of insufficient sleep on the RNA present in blood. RNA is made from “active” genes and is used to make proteins and other products within the cell. Participants were invited to a sleep centre (a research facility dedicated to investigating sleep and related issues) and were then scheduled to have one week of insufficient sleep or to have sufficient sleep. They were then crossed over to the other sleep regime.
What did the research involve?
26 people participated in the previous study.
After two nights where participants became accustomed to the sleep centre, participants were scheduled to seven nights of insufficient sleep, where they were allowed sleep opportunities of six hours per 24 hours (participants got 5.7 hours sleep on average per night) or seven nights of sufficient sleep, where they were allowed sleep opportunities of 10 hours per 24 hours (participants got 8.5 hours sleep on average per 24 hours).
Immediately after the week of insufficient sleep and the week of sufficient sleep the participants had to stay awake for an extended period (39-41 hours, total sleep deprivation). Researchers took 10 blood samples at three-hourly intervals.
The participants were allowed a 12-hour “sleep opportunity” to recover.
After participants had completed one sleep regime, they were crossed-over to the other one after a break of at least 10 days.
From the blood samples they had taken, the researchers looked at what genes were being “active” – (RNA was being made from them).
The researchers looked to see whether there were differences in the genes that were active after the week of insufficient sleep compared to after the week of sufficient sleep.
What were the basic results?
The activity of 711 genes was changed after a week of insufficient sleep.
The number of genes with a “circadian rhythm”, meaning that their activity varied over an approximate 24 hour cycle, was reduced after a week of insufficient sleep. In addition, the genes still displaying a circadian rhythm had smaller variations in their activity.
During the period where participants had to stay awake for an extended period, more genes were affected in people who had just experienced a week of insufficient sleep compared to those who had experienced a week of sufficient sleep.
The researchers say that the genes affected by the week of insufficient sleep are involved in chromatin modification (the modification of proteins and DNA that make up the nucleus of a cell), the regulation of gene activity, macromolecular metabolism (metabolism of carbohydrates, proteins, fats), and inflammatory, immune and stress responses.
How did the researchers interpret the results?
The researchers concluded that, “one week of insufficient sleep alters gene expression in human blood cells, reduces the amplitude of circadian rhythms in gene expression, and intensifies the effects of subsequent acute total sleep loss on gene expression. The affected genes are involved in chromatin remodelling, regulation of gene expression, and immune and stress responses. The data imply molecular mechanisms mediating the effects of sleep loss on health and highlight the interrelationships between sleep homeostasis, circadian rhythmicity, and metabolism.”
Conclusion
A previous small study from this research group has found that insufficient sleep alters gene expression and circadian rhythms, and the response to acute total sleep loss.
This alteration could potentially lead to a larger knock-on effect at higher biological levels.
There have been previous studies suggesting shift work was associated with an increased risk of certain chronic diseases such as diabetes and breast cancer although the evidence presented in the studies is largely inconclusive.
It seems that the two studies discussed provide some clues as to how the body may be affected by disrupted sleep patterns (see box for more on this as yet unpublished study). However, we have a long way to go before we understand the exact impact of different patterns of sleep on people’s health.
