Ella Lafata ’20 and Brad Arras ’20


Are you a student? Do you work night shifts? Are you a night owl and stay awake through the night? 

What if I told you that if you sleep less than 6.5 hours a night, which many of us do, your body reacts to the lack of sleep. And that your body does so by cells altering their DNA’s structure. Would you be surprised? These modifications can affect your emotions and reactions throughout your sleep-deprived day. Furthermore, the change in DNA can be passed down a generation, to the children of those who were often sleep deprived. 

Crazy right? More than ⅓ of Americans report being sleep deprived every night. Students or night-shift workers often pull “all-nighters”, where they are awake throughout the entire night, sleeping zero hours. This discussion focuses on the changes within our DNA due to sleep deprivation and the effects caused by the DNA modifications. The studies mentioned throughout the paper focus on the body’s epigenetic modifications due to sleep deprivation using human blood samples and rat and mouse models. 

Think of the body as a car while the genome is an instruction manual describing how it functions properly. Every cell in the body has a copy of the full instruction manual. However, pancreatic cells only read the section of the manual relating to pancreatic functions. Pancreatic cells will ignore the sections about other organs, such as the kidneys, since the kidney cells only read the section which develops and maintains the kidney. The instructions within the manual (genome) can be thought of as DNA. Envision DNA as a long string wrapped around bead-like proteins called histones within each and every cell. DNA wraps itself around these beads/histones so it can be condensed within the nucleus of each cell. Chromatin is the structure formed by the DNA wrapping around the histones within a cell’s nucleus.

Chromatin structure can be altered in our DNA through epigenetic modifications. These modifications are not a change within the actual sequence of our DNA, but it does affect how well the sequence is able to be transcribed, translated, and able to obtain a function in our body by opening up or closing off the chromatin structure. We can think of the beads on a string structure resembling a hair dryer’s cord. The more you pull on the cord, the more open the cord’s curls become. Yet, if you give the cord more slack, the cord’s curls become tighter and more abundant. Chromatin works the same way! The DNA itself or the histone proteins can become chemically modified making the curls within our chromatin become more or less loose. 

When chromatin is less tightly curled, the DNA sequence is more open to allow for the DNA to be read, and thus transcribed more readily. DNA transcription gives us RNA, which is then translated into a protein that obtains a function in our body. When chromatin is more tightly curled, the DNA is more closed off and less likely to be transcribed to make RNA. Areas of DNA sequences that are transcribed and eventually make specific proteins are called “genes”. Genes are like chapters to our book of life. Each chapter has a message about something important to the body. For example, a certain chapter/gene will have a message detailing what protein is needed for us to see in the dark. When that gene is transcribed and translated, that necessary protein will be made for our body. However, epigenetic modifications are able to effect the transcription of certain genes by adding or removing chemical elements to the chromatin. The epigenetic elements act like a stop light with either green or red lights, mediating transcription accessibility by making the chromatin become more or less tightly curled, displayed in Figure 1.

Figure 1:

Generally speaking, being sleep deprived means sleeping equal to or less than 6.5 hours a night. Some people are chronically sleep-deprived, such as people with insomnia. Others may be sleep deprived for only one night out of the week, but that one night also affects your body. Sleep deprivation can be caused by a variety of things, such as work/lifestyle, health conditions, or by using stimulant drugs. Sleep deprivation then impacts our bodies epigenetically, including through histone modifications and DNA methylation, as depicted in Figure 2. These modifications lead to a difference in protein and gene expression which affects our physiology, emotions, and our brain functioning. In discussing the epigenetics of sleep deprivation, there are three bodily functions that are affected by the DNA’s epigenetic modifications: circadian rhythms, the brain’s synaptic function, and fatty acid synthesis. 

Figure 2: 

Memory and Cognition: 

Did you know that your body has its own internal clock? The clock is your circadian rhythm. This biological clock helps you feel alert during the day, hungry at mealtimes, and sleepy at night. The circadian rhythm influences bodies to release certain hormones throughout our 24-hour clock. Genes that regulate the circadian rhythm are CLOCK, CRY1, and PER1. While the CLOCK gene is not correlated with any confirmed epigenetic modifications due to sleep deprivation, both CRY1 and PER1 display hypermethylation after sleep deprivation. Hypermethylation is an epigenetic modification where a chemical tag called a “methyl group” is added on top of the gene’s DNA sequence. The addition of a methyl group acts like a red light for DNA transcription, causing the chromatin/power cord to curl more tightly. Because of the hypermethylation, the CRY1 and PER1 genes are less likely to be transcribed. This tightly wound cord is associated with memory impairment, and there is a histone modification which leads to the same result.

In a different research study focusing on sleep deprivation in rats, the sleep deprived rats displayed reduced acetylation of histones associated with the BDNF IV gene. Histone acetylation is an epigenetic modification on a histone, a protein associated with DNA. Acetylation is a chemical reaction where the positive charge normally on a histone protein is removed, prompting less interactions between the histones and DNA. Acetylation of histone proteins resembles a green light, promoting DNA transcription. The decrease in DNA-histone interaction is analogous with the power cord becoming more loose and free. BDNF IV is an important gene that yields a protein involved in neuron growth and maintenance. Acetylation of BDNF results in greater expression of the protein, due to the lack of interactions between DNA and histones. However, the reduction in acetylation behaves like a red light for DNA transcription due to the increased DNA-histone interactions, resulting in a more tightly wound, inaccessible cord. Thus, when sleep deprived, we produce less BDNF proteins. These proteins are important because they work within our brains to promote neuron growth, maturation, and maintenance. So far, we’ve discussed how sleep deprivation is associated with hypermethylation of circadian rhythm genes and deacetylation of the BDNF IV gene, but there are other ways that sleep deprivation affects the brain and its functioning. 

Various genes involved in nervous system development were also found to be highly methylated in sleep-deprived mice. Rab11b, a gene important in nervous signaling, was found to have increased methylation, tightening the DNA’s chromatin curls and reducing the gene’s protein expression, leading to decreased memory function in no-sleep mice. Nlgn3 is another impacted gene which is important in the transport of nervous signals from the brain. Sleep-deprived mice displayed another epigenetic modification called hydroxylation upon the Nlg3 gene. Hydroxylation enlists a red light for transcription by reducing access to the DNA by adding a hydroxyl group directly to the gene’s DNA sequence. The added hydroxyl group tightens the hair dryer’s power cord in a similar way as methylation. All of these impacts on various functions of your nervous system cause deficits in memory formation and cognitive control, although it is not the only physical change on your body due to loss of sleep.

Fatty Acids and Obesity:

Sleep is vital to parts of your body completely separate from neuronal pathways, so to complete the argument that an all-nighter can impact your personal health, we’ll dive into some research linking one-night total sleep deprivation (no sleep) to obesity in previously healthy young men. Stearoyl-CoA desaturase (SCD1) is an enzyme that is important in fatty acid processing. Think of SCD1 as a shuttle which stores fatty acids in your body, with more expression of the gene causing a greater risk of obesity. The sleep deprived men showed hypermethylation of this gene. The confusing concept here is that instead of the methylation tightening the power cord that is our DNA, methylation of SCD1 loosens the DNA for the gene, allowing for greater expression of the enzyme/shuttle. Thus, in this scenario hypermethylation of the SCD1 gene acts like a green light, promoting transcription. Now, with increased levels of the SCD1 enzyme caused by no sleep, results exhibit that your body is hindered in its ability to break down fat. Because of the body’s inability to process fat, it instead stores the unprocessed fat within our body’s fat deposits, called adipocytes. This increases the risk of obesity for sleep deprived people. This research on fatty acid processing frames an interesting window into how sleep deprivation can alter your body’s ability to process and store fat.

In conclusion, we can see that there are serious impacts on our bodies after just one night of sleep loss and chronic sleep deprivation. Through various epigenetic modifications, such as methylation, acetylation, and hydroxylation, we can view numerous impacts on bodily functions such as cognitive development and fat processing onset by short-term sleep deprivation. Utilizing this information, we can make a more informed decision on whether to stay up that extra time or get some rest before an exam, or even identify what the true cause is behind unexpected weight gain. These studies all serve as monumental stepping stones in elucidating the truth about sleep deprivation’s full impact on health, both in long and short-term scenarios, paving the way for further sleep deprivation research.

References

  1. Gaine ME, Chatterjee S, Abel T. Sleep Deprivation and the Epigenome. Front Neural Circuits. 2018;12:14. Published 2018 Feb 27. doi:10.3389/fncir.2018.00014
  2. Massart R, Freyburger M, Suderman M, et al. The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes. Transl Psychiatry. 2014;4(1):e347. Published 2014 Jan 21. doi:10.1038/tp.2013.120
  3. Skuladottir GV, Nilsson EK, Mwinyi J. One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men. Published 2016 Aug 26. Lipids Health Dis. Doi: 10.1186/s12944-016-0309-1.