Short-Term Sleep Loss Alters DNA Methylation of Clock Genes

Sleep is crucial to our well-being and helps in the process of learning and memory formation. Without proper sleep we can feel moody, irritable, and have difficulty solving problems. We can even be less creative when we don’t get enough sleep. Now, research published in the Journal of Clinical Endocrinology and Metabolism is showing us that just one night of poor sleep can lead to epigenetic changes to our DNA, specifically to our “clock genes” which control our circadian clock. The circadian clock is a regulatory process in accordance with the day-night cycle and this disturbance could ultimately lead to metabolic disruptions and health issues.

Researchers at Uppsala University and the Karolinska Institute conducted a randomized clinicial study on acute sleep loss and DNA methylation changes in 15 healthy men. For 2 nights, the participants stayed at the lab for the experiment. After the first night, some slept normally for 8 hours in one of the two sessions, while others were kept awake in the other session. The researchers wanted to reduce any impact that outside variables might’ve had, such as light conditions, activity levels, and food intake, so these were tightly controlled during the study. Even when the men were not allowed to sleep, they were restricted to the bed.

On the subsequent morning, tiny tissue samples were taken from two types of tissue that play a significant role in regulating metabolism and controlling blood sugar levels – subcutaneous adipose tissue from the stomach and skeletal muscle from the thigh. In addition, their blood was also analyzed before and after they drank a sugar solution to record their insulin sensitivity.

The researchers found that the activity and regulation of core clock genes – BMAL1, CLOCK, CRY1, PER1 – was changed after only a single night of losing sleep. They identified increased DNA methylation as a result of one night of wakefulness and an alteration in gene expression. DNA methylation is an important epigenetic mechanism known to play a central role in regulating the expression of genes via the addition of a methyl group onto the DNA.

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“Previous research has shown that our metabolism is negatively affected by sleep loss, and sleep loss has been linked to an increased risk of obesity and type 2 diabetes. Since ablation of clock genes in animals can cause these disease states, our current results indicate that changes of our clock genes may be linked to such negative effects caused by sleep loss,” said the study’s lead author, Jonathan Cedernaes, from Uppsala University.

“As far as we know, we are the first to directly show that epigenetic changes can occur after sleep loss in humans, but also in these important tissues,” said Dr. Cedernaes. “It was interesting that the methylation of these genes could be altered so quickly, and that it could occur for these metabolically important clock genes.”

The DNA methylation changes were different in the skeletal tissue compared to the adipose tissue, which might indicate a desynchronization of the molecular clock between the two. Dr. Cedernaes explained: “As such, ‘clock desynchrony’ between tissues has been linked to metabolic pathologies, this could suggest that these tissue-specific changes were linked to the impaired glucose tolerance that our participants demonstrated after the night that they had been kept awake.”

The scientists are unsure of how persistent the DNA methylation changes are, as epigenetic marks are known to fluctuate and this study only covered a short time period. Dr. Cedernaes indicated that these epigenetic changes may be reset once the individual is able to sleep well for a few days, or alternatively, the molecular marks may function as metabolic memory and persist over time. Previously, similar epigenetic changes have been detected in shift workers and those inflicted with type 2 diabetes, hinting that sleep loss experienced by these individuals could result in long-term alterations to the genome of metabolism-associated tissues.


Source: Cedernaes, J., Osler, M.E., Voisin, S., Broman, J., Vogel, H., Dickson, S.L., Zierath, J.R., Schiöth, H.B., Benedict, C. (2015). Acute sleep loss induces tissue-specific epigenetic and transcriptional alterations to circadian clock genes in men. The Journal of Clinical Endocrinology & Metabolism, 100(9).

Reference: Uppsala University. One night of sleep loss can alter clock genes in your tissues. 20 Jul 2015. Web.

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About Bailey Kirkpatrick 164 Articles
Bailey Kirkpatrick is a science writer with a background in epigenetics and psychology with a passion for conveying scientific concepts to the wider community. She enjoys speculating about the implications of epigenetics and how it might impact our perception of wellbeing and the development of novel preventative strategies. When she’s not combing through research articles, she also enjoys discovering new foods, taking nighttime strolls, and discussing current events over a barrel-aged sour beer or cold-brewed coffee.


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