When the circadian clock is disrupted by various outside factors (light, food, etc.) this can lead to certain disease states. This can be seen in the figure below which shows how external stimuli can affect disease states through certain organs and the circadian clock (Figure 1). There are various ways in which circadian clock disruption can cause diseases and even cancer: shortened sleep duration, mutated clock genes, and other environmental factors.
First, shorter sleep duration (having interrupted sleep or not long enough sleep) has been associated with obesity and diabetes (Asher & Sassone-Corsi, 2015). This is due to the fact that the circadian rhythm influences the endocrine systems ability to regulate insulin resistance which can lead to diseases like obesity and diabetes (Reinke & Asher, 2019). If the endocrine system loses part of its ability to regulate insulin, then that throws off the homeostasis of glucose regulation.
The second way the circadian clock can alter disease states is through clock genes (genes that control and regulate the circadian clock). Polymorphisms in clock genes are associated with higher risk of obesity, hypertension, and type 2 diabetes (Jagannath et al., 2017). This being said, there are genetic reasons linked to the circadian clock that can cause disease states to arise that may be out of a person’s control.
The third way the circadian clock can cause disease is through cancer. Cancer is one of human’s most feared diseases and can be influenced by many external and internal factors, especially those surrounding the circadian clock. Circadian disruption has been classified as a carcinogen and is a risk factor for developing cancer (Shafi & Knudsen, 2019). Clock genes and circadian clock disruptions both have an effect on cancer risk. First, clock genes are in control of many pathways that regulate DNA damage and repair which is why that are able to affect cancer susceptibility (Benna et al., 2017).
Equally important are the environmental factors that affect circadian clock which in turn affect cancer risk. Light at night exposure, late-eaters, jet lag, shift work, and sleep disruption all lead to an increase in cancer risk, including breast, prostate, lung, ovary, pancreas, colon, and liver cancer (Masri & Sassone-Corsi, 2018; Shafi & Knudsen, 2019). This is further proven by these two interesting facts: loss of circadian control is related to less response to cancer treatments, and visually impaired people who are insensitive to light in their environment have a lower cancer risk overall (Shafi & Knudsen, 2019). The moral of the story is do not be like the typical college student; please have good sleep hygiene!
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Figure
1. Stimuli affect the different organ systems, processes, and disease states through
the SCN (suprachiasmatic nuclei). Patke, A., Young, M. W., & Axelrod, S.
(2020). Molecular mechanisms and physiological importance of circadian
rhythms. Nature reviews. Molecular cell biology, 21(2),
67–84. https://doi-org.dml.regis.edu/10.1038/s41580-019-0179-2 |
Asher, G., &
Sassone-Corsi, P. (2015). Time for food: the intimate interplay between
nutrition, metabolism, and the circadian clock. Cell, 161(1),
84–92. https://doi-org.dml.regis.edu/10.1016/j.cell.2015.03.015
Benna, C., Helfrich-Förster, C., Rajendran, S.,
Monticelli, H., Pilati, P., Nitti, D., & Mocellin, S. (2017). Genetic
variation of clock genes and cancer risk: a field synopsis and
meta-analysis. Oncotarget, 8(14), 23978–23995. https://doi-org.dml.regis.edu/10.18632/
oncotarget.15074
Jagannath, A., Taylor,
L., Wakaf, Z., Vasudevan, S. R., & Foster, R. G. (2017). The genetics of
circadian rhythms, sleep and health. Human molecular genetics, 26(R2),
R128–R138. https://doi-org.dml.regis.edu/10.1093/hmg/ddx240
Masri, S., &
Sassone-Corsi, P. (2018). The emerging link between cancer, metabolism, and
circadian rhythms. Nature medicine, 24(12), 1795–1803. https://doi-org.dml.regis.edu/10.1038/s41591-018-0271-8
Patke, A., Young, M. W.,
& Axelrod, S. (2020). Molecular mechanisms and physiological importance of
circadian rhythms. Nature reviews. Molecular cell biology, 21(2),
67–84. https://doi-org.dml.regis.edu/10.1038/s41580-019-0179-2
Reinke, H., & Asher,
G. (2019). Crosstalk between metabolism and circadian clocks. Nature
reviews. Molecular cell biology, 20(4), 227–241.
https://doi-org.dml.regis.edu/10.1038/s41580-018-0096-9
Shafi, A. A., &
Knudsen, K. E. (2019). Cancer and the Circadian Clock. Cancer research, 79(15),
3806–3814. https://doi-org.dml.regis.edu/10.1158/0008-5472.CAN-19-0566
Really interesting post, Molly! It's interesting to think about how lack of sleep can impact so many different pathways in our bodies, because everything is so connected. Your post about how sleep deprivation can affect our vulnerability to disease made me think about how it might also affect our ability to recover from disease. I found a study that found that sleep deprivation also prevented affective recovery from negative physiological events (Hamilton et al., 2008). In another study, in mice, both acute and chronic sleep deprivation delayed their recovery to colitis (Tang, et al., 2009). Looking at how sleep can negatively affect our bodies really gives us motivation to improve our sleep hygiene! No more all nighters!!
ReplyDeleteHamilton, N. A., Affleck, G., Tennen, H., Karlson, C., Luxton, D., Preacher, K. J., & Templin, J. L. (2008). Fibromyalgia: the role of sleep in affect and in negative event reactivity and recovery. Health Psychology, 27(4), 490.
Tang, Y., Preuss, F., Turek, F. W., Jakate, S., & Keshavarzian, A. (2009). Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis. Sleep medicine, 10(6), 597-603.
Molly, I love this post! I think that sleep patterns are something really interesting to think about. When you mentioned shift work, I immediately thought about nurses. Since this is their profession, I was very curious as to what nurses could do to combat circadian disruption and light at night exposure. I found an article in Chronobiology International that discussed a light-based intervention that helped improve melatonin levels and quality of sleep for nurses. Researchers had them undergo bright light exposure before night shifts, avoid light after their shifts by using sunglasses, and nap during “ideal times” that were defined by the researchers. After these treatments, the nurses reported less fatigue, better sleep, a more positive mood, and fewer work errors.
ReplyDeleteOlson, J. A., Artenie, D. Z., Cyr, M., Raz, A., & Lee, V. (2020). Developing a light-based intervention to reduce fatigue and improve sleep in rapidly rotating shift workers. In Chronobiology International: The Journal of Biological & Medical Rhythm Research (Vol. 37, Issue 4, pp. 573–591). https://doi-org.dml.regis.edu/10.1080/07420528.2019.1698591
As someone who enjoys getting their sleep, this post really resonated with me. The term "sleep hygiene" is something I never fully considered before reading this post. I snack pretty late into the night and am often exposed to light sources up until I shut my eyes. Additionally, I thought of jet lag and how much people who travel often must feel considering that they must be constantly faced with disruptions to sleep. Thanks for a good read, Molly! I'll definitely rethink my habits after this.
ReplyDeleteI was very interested to hear about all the ways sleep disruption can lead to cancer. In looking more into possible mechanisms of action, I found that a normal 24-circadian rhythm is important for regulating thyroid function which can have many downstream effects on the regulation of various genes. The disruption of this pathway through any of the ways mentioned in your blog post could lead to the disruption of genetic regulation, leading to cancer. Hopefully additional research in the future can provide further insight into the details of how this pathway works.
ReplyDeleteIkegami, K, et al. (2019). Interconnection between circadian clocks and thyroid function. Nature Reviews Endocrinology, 15(10): 590-600.