People often struggle if they have to adjust to working the night shift, but their genes have even more trouble. According to a new study from McGill University, genes that are accustomed to daytime rhythm usually fail to adapt to nighttime rhythm, possibly contributing to health problems such as diabetes, obesity, and cardiovascular disease—disorders that are more frequently seen in night-shift workers.
Many genes that regulate important biological processes have a sort of sleeping/waking cycle, one that increases or decreases gene expression over a 24-hour period. This cycle may be assessed globally, for all genes, via characterization of the transcriptome, the set of all mRNAs expressed by the genome.
In the McGill University study, transcriptomes were evaluated for eight healthy volunteers who were artificially subjected to a five-day schedule simulating night-shift work. In a time-isolation room, the volunteers were deprived of any light or sound cues characteristic of the time of day and were not allowed to use their phones or laptops.
On the first day and after the last night shift, the volunteers provided blood samples at regular intervals for a period of 24 hours. These samples were then subjected to a transcriptomic analysis that encompassed the expression of more than 20,000 genes.
The results of this work appeared May 7 in the Proceedings of the National Academy of Sciences (PNAS), in an article entitled “Simulated Night Shift Work Induces Circadian Misalignment of the Human Peripheral Blood Mononuclear Cell Transcriptome.” The article describes how imposing a night-shift schedule dampened gene expression rhythms, resulting in a “desynchrony between rhythmic transcripts and the shifted the sleep/wake cycle.”
“Almost 25% of the rhythmic genes lost their biological rhythm after our volunteers were exposed to our night-shift simulation,” noted Nicolas Cermakian, Ph.D., director of the Laboratory of Molecular Chronobiology at the Douglas Mental Health University Institute (DMHUI) and a full professor at McGill University's Department of Psychiatry. “And 73% did not adapt to the night shift and stayed tuned to their daytime rhythm. Less than 3% partly adapted to the night-shift schedule.”
“We now better understand the molecular changes that take place inside the human body when sleeping and eating behaviors are in sync with our biological clock,” added Diane B. Boivin, M.D., Ph.D., a researcher at DMHUI and another author of the PNAS paper. “For example, we found that the expression of genes related to the immune system and metabolic processes did not adapt to the new behaviors.”
“Functional analysis,” the authors of the PNAS paper wrote, “revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways.”
As the study was conducted under highly controlled conditions in the laboratory, future research should extend these findings by studying the gene expression of actual night-shift workers whose physical activity, food intake, and timing of sleep might differ from one another. This could also be applied to other people that are at risk of experiencing biological clock misalignment, such as travelers crossing time zones on a frequent basis.
“We think the molecular changes we observed potentially contribute to the development of health problems like diabetes, obesity, and cardiovascular diseases more frequently seen in night-shift workers on the long term,” explained Dr. Boivin. However, she adds this will require further investigation.
