Question: As just an average college student, I often find myself going to bed just shy of the break of dawn, just to wake up a few hours later for morning classes, This leaves me drowsy and exhausted throughout the day. Boykin, in a thesis on sleep deprivation from 2014, notes that over 75% of college students felt sleepy on a weekly basis while 44% were tired for at least 3 days each week. This is a problem that many college students, like me, face. But while I understand the effects of sleep deprivation on a physical level, how does sleep deprivation manifest on a molecular scale?

Answer: Clinton et al. note that many molecules participate in sleep regulation, and that sleep deprivation can lead to changes in the expression of these molecules. Some of these molecules include the cytokines IL1 and tumor necrosis factor alpha (TNF). Expression of IL1 and TNF is increased in tissue damage and infection as well as sleep loss. Clinton et al. concluded in experiments on sleep regulation that inhibiting these cytokines decreases sleepiness while injecting IL1 and TNF in normal mice increase the intensity of sleep and can induce a sleep like state in parts of the brain. The implication is that IL1 and TNF regulate sleep and tiredness. Reutrakul and Van Cauter, in their 2014 publication on sleep and metabolism, note that sleep loss is linked to an increased risk of type 2 diabetes due to abnormalities in glucose metabolism and reduced sensitivity to insulin sensitivity (leading to increased insulin levels). This link between sleep and diabetes is also strengthened by evidence of altered melatonin levels causing diabetes. Melatonin, a hormone that helps regulate sleep by inducing sleepiness in dim light, also plays a role in regulating insulin secretion. Reutrakul and Van Cauter also note that leptin and other appetite regulating hormones are reduced, leading to an increase in appetite.  Not only can lack of sleep can cause harmful consequences, but sleep disruptions such as disturbances to circadian rhythm can also be harmful. For example, in a 2013 article on sleep and schizophrenia, Monti et al. conclude that disruptions in the circadian rhythm is linked to schizophrenia through a change in the melatonin receptor. Although this conclusion implies correlation and not causation. In 2010, Langa et al. demonstrated in a study on circadian rhythm and the immune system that disruptions in the circadian rhythm lead to a weakened immune system. Lowered cortisol levels during sleep lead to increased helper T cell production and activity. Without sleep, the Langa study demonstrates that helper T cell activity is lower leading to a weakened immune system. While these points only cover a small portion of the effects of sleep deprivation, these studies describe our current understanding of the biomolecular mechanisms leading to various consequences of sleep disturbance, ranging from fatigue and exhaustion to chronic diseases such as obesity and diabetes.

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1) Boykin, Jade Catherine, “Physiological and Biochemical Consequences of Sleep Deprivation.” University Honors Program Theses. Paper 33 (2014). Web. 16 June 2016.

2) Clinton, James M. et al. “Biochemical Regulation of Sleep and Sleep Biomarkers.” Journal of Clinical Sleep Medicine, 7.5 (2014): S38-S42. Web. 15 June 2016. Ddoi:10.5664/jscm1360.

3) Reutrakul, Sirimon & Van Cauter, Eve. “Interactions Between Sleep, Circadian Function, and Glucose Metabolism: Implications for Risk and Severity of Diabetes.” Annals of the New York Academy of Sciences, 1311 (2014): 151-173. Web. 16 June 2016. Doi:10.1111/nyas.12355.

4) Monti, M. Jaime et al. “Sleep and Circadian Rhythm Dysregulation in Schizophrenia.” Progress in Neuro-Psychophramacology and Biological Psychiatry, 43 (2013): 209-216. Web. 21 June 2016. Doi: 10.1016/j.pnpbp.2012.12.021

5) Lange, Tanga, Dimitrov, Stoyan, & Born, Jan. “Effects of Sleep and Circadian Rhythm on the Human Immune System.” Annals of the New York Academy of Sciences, 1193 (2010): 48-59. Web. 21 June 2016. Doi: 10.1111/j.1749-6632.2009.05300.x