Chronic, insufficient sleep can negatively affect immune cells, which can lead to inflammatory disorders and cardiovascular disease, according to a new study from the Icahn School of Medicine at Mount Sinai. Specifically, consistently losing an hour and a half of sleep per night potentially increases risk.
The research, published September 21 in the Journal of Experimental Medicine, is the first to show that sleep alters the DNA structure inside immune stem cells that produce white blood cells, also known as immune cells, and that this can have a lasting impact on inflammation and contribute to inflammatory diseases. Immune cells fight infection, but if the number of these cells gets too high, they overreact and cause inflammation. The study is also the first to show that catch-up sleep does not reverse the effects of sleep disruption.
“This study begins to identify the biological mechanisms that link sleep and long-term immune health. It shows that in humans and mice, disrupted sleep has a profound influence on the programming of immune cells and the rate of their production, causing them to lose their protective effects and worsening infections – and these changes are long-lasting. This is important because it is another key observation that sleep reduces inflammation and, conversely, interrupting sleep increases inflammation,” says lead author Filip Swirski, PhD, director of the Institute of Icahn Mount Sinai Cardiovascular Research. “This work underscores the importance for adults of getting seven to eight hours of regular sleep a day to help prevent inflammation and disease, especially for those with underlying medical conditions.”
A team of researchers analyzed 14 healthy adults who regularly sleep eight hours a night. First, the researchers monitored them sleeping for at least eight hours a night for six weeks. They took their blood and analyzed their immune cells. Then the same group of adults cut their sleep time by 90 minutes every night for six weeks and had their blood and immune cells retested. At the end of the study, the researchers compared blood and cell samples from a full night’s sleep and from restricted periods of sleep. All participants showed significant changes in their immune cells (also called haematopoietic cells) due to lack of sleep – there were more of them and DNA structure was altered. After six weeks of sleep restriction, they had an increased number of immune cells.
The researchers also analyzed sleep in mouse models. Groups of mice were either allowed to sleep undisturbed or had sleep fragmentation, where they were awake all night for 16 weeks. Then the mice with sleep fragmentation went through uninterrupted sleep recovery for ten weeks. The researchers took immune stem cells and immune cells from mice during these undisturbed, fragmented, and dormant recovery phases, analyzed and compared them at the end of the experiment. The results in mice were consistent with the results in humans. They showed that all of the mice with fragmented sleep showed significant changes in their immune stem cells, producing increased numbers of immune cells, and also showed evidence of rewiring and reprogramming. A notable finding from the group of mice was that even after recovering from sleep, the immune stem cells retained this rewiring structure and continued to produce additional white blood cells, making the mice susceptible to inflammation and disease.
“Our results suggest that sleep recovery is not able to completely reverse the effects of poor quality sleep. We can detect a molecular fingerprint of insufficient sleep in immune stem cells, even after weeks of sleep This molecular imprint can cause cells to react inappropriately, leading to inflammation and disease,” says co-lead researcher Cameron McAlpine, PhD, assistant professor of medicine (cardiology) at Icahn Mount Sinai. surprisingly, not all stem cell clusters responded equally to lack of sleep.Some stem cell clusters proliferated and increased in number, while other clusters became smaller.This reduction in overall diversity and aging immune stem cell population is a significant contributor to inflammatory diseases and cardiovascular disease.
The National Heart, Lung and Blood Instituteand the National Center for the Advancement of Translational Sciences part of the National Institutes of Health, helped fund this study.
Figure: The impact of insufficient sleep on immune stem cells
The description: The left side of the figure shows the sleep time of the humans in the study. Participants in the sleep restriction group (the red dots) slept less over the six weeks. The right side of the figure stem cell analysis. The first graph shows that people in the sleep restriction group (again red dots) had more stem cells. The rest of the figure represents the structure and reprogramming of DNA. The red and blue colors show the locations of the genome that have been rewired. The lower “spikes” are specific genes that the researchers looked at and show rewiring in those places.
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