Time Off Reverses the Adverse Epigenetic Effects of Shift Work Disorder

Shift work has been on the rise over the past decade as the demand for real-time goods and services increases globally. This growth has never been more evident than during the past year, as the pandemic forced many people to rely on essential workers for increased medical care, home delivery goods, and other high-demand consumer items. 

However, working odd hours, especially through the night, poses fundamental challenges to the body. Not only does it disrupt circadian rhythm or the body’s internal clock, but the resulting sleep deprivation also increases a person’s risk for developing a serious mental or physical condition. Yet, our understanding of how this type of sleep loss affects us on a molecular level that leads to adverse health consequences is not fully understood.

Because the human DNA methylome is responsive to environmental influences, a group of researchers from Finland decided to conduct a study to investigate the DNA methylation changes found in shift workers. To analyze the dynamic character of this modification, they looked into the biological processes that underly recovery from shift work disorder (SWD) — a medical sleep condition primarily associated with late-night or early-morning shift workers. Their goal was to see what impact vacation, or time off a shift schedule, had on restoring normal DNA methylation patterns. Their results were published in the open-access online journal, Scientific Reports.

DNA methylation is one of several epigenetic mechanisms that play a critical role in regulating gene expression. Potentially reversible, it occurs with the chemical addition of a methyl group to DNA, modifying the function of genes without changing the core DNA sequence. While methylation status can be linked with environmental conditions, short-lived genetic modifications due to DNA methylation are not widely known. The current study is one of only a few that has recorded evidence of changes in DNA methylation patterns in humans within a few months.

The effects of sleep deprivation on the methylome have been previously studied and proven to induce notable changes. In earlier posts, we’ve reviewed how sleep deprivation epigenetically lowers the body’s antioxidant levels and how skipping sleep triggers an epigenetic change to metabolism. The authors here also conducted a genome-wide analysis of DNA methylation concerning sleep deprivation in a prior investigation and found a distinctive pattern of differentially methylated positions (DMPs) among people suffering from sleep disturbances.

This study included a methylome-wide analysis of blood samples taken from airline workers during work and after taking at least two weeks of vacation. A total of 32 workers participated in the experiment, 21 of whom suffered from SWD and 11 without the sleep disorder for control.

The scientists identified DNA methylation differences in the SWD group compared to the control.  A loss of methylation or hypomethylation was observed in those experiencing insufficient sleep. When measuring the methylation levels in SWD groups after vacation, they found that rest and recovery taken during the time off restored DNA methylation level to a healthy state in the SWD group.

“Based on the results, we can deduce that changes to the DNA methylation of white blood cells are associated with shift work disorder,” said Alexandra Lahtinen, a researcher from the University of Helsinki and first author of the study. “These changes, such as low methylation levels observed during the work period, are probably linked to sleep deprivation and related inflammatory consequences which DNA changes may mediate.”

The findings from this study demonstrate DNA methylation’s dynamic nature. The methylation differences were detected primarily in processes related to NMDA receptor activity. In particular, the researchers pinpointed GRIN2C, CREB1, and CAMK2B CpG sites as presumed important markers of recovery in a shift worker with SWD.

As we all know, getting enough sleep is important for everyone. However, it is even more critical when a person is subjected to irregular working conditions, causing long-term sleep deprivation. The good news is that downtime away from work may overturn some of the adverse changes caused by shift-related sleep loss.  More research is needed to validate these results. The team suggests larger cohorts could help uncover the regulatory mechanism involved in SWD recovery and validate the health-related potential of vacation time.

Source: Alexandra Lahtinen, et al. Differential DNA methylation in recovery from shift work disorder. Scientific Reports, 2021; 11(1).

Reference:  A sleep disorder associated with shift work may affect gene function: Going on holiday has a restorative effect on changes in DNA. University of Helsinki, February 22, 2021.

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