A majority of organisms have developed internal circadian clocks, which allow the organism to anticipate cycles of light and temperature in the environment, and to synchronize their behavior and biological processes to these cycles. In today’s society, we see a prevalence of “social jet lag”, which involves irregular schedules of sleeping and eating. This social jet lag is a form of chronic circadian misalignment (CCM), because it involves a desynchronization between behavior and the endogenous circadian rhythms dictated by environmental cues (Boomgarden, et al., 2019). Students and shift workers are among those who are most affected by these irregular schedules, and the fact that this is so common in modern society emphasizes the need for investigations into the consequences of chronic circadian misalignment. Some such studies have been conducted, and led to evidence that CCM can be linked to problems such as obesity, diabetes, cancer, mood disorders, and increased mortality rates (Boomgarden et al., 2019).
Dr. Cavanaugh began his talk by focusing on many of the studies that have been conducted on the effects of CCM. He discussed the fact that many rhythms in biological and behavioral processes are synchronized to the internal circadian clock such as hormone release, body temperature, reaction time, muscle strength, and alertness. He also talked about a study that demonstrates an association between chronic jet lag and short term memory deficits. This study involved an experimental group made up of flight attendants, and a control group that was made up of members of the ground crew from the same airline. When these groups performed a delayed match-to-sample task, flight attendants performed significantly worse than the members of the ground crew, and poor performance correlated with number of years working as a flight attendant. In relation to Dr. Cavanaugh’s talk, an article in Time magazine entitled “Can You Really Catch Up on Lost Sleep? Here's What the Science Says” discusses the the role that circadian rhythms play in terms of consequences of sleep loss. In this article, the authors discuss how sleep loss results in an accumulation of sleep debt, even for seemingly minimal amounts of sleep loss. Dr. Cathy Goldstein explains that the reason behind this, and why it is so difficult to make up for lost sleep, is due to a disruption of one’s circadian clock through irregular sleep schedules (Ducharme, 2019). In this way, one cannot make up for an all-nighter simply by sleeping in later on the weekend because this falls under what Dr. Cavanaugh referred to as “social jet lag”, and would result in a further disruption of one’s circadian rhythms. In the article, Dr. Goldstein goes on to discuss how one’s circadian clock begins to secrete melatonin, a sleep-promoting hormone, around 9 p.m., and continues to maintain high levels of this hormone until the morning when levels drop off (Ducharme, 2019). This connects to Dr. Cavanaugh’s discussion of how the endogenous circadian clock dictates biological cycles such as hormone levels, and the patterns of melatonin release discussed in the Time article provides a specific example of such cycling.
The Time magazine article also talks about many of the health consequences that have been linked to circadian disruption. In this article, Dr. Goldstein mentions associations between irregular sleep schedules and cancer, shortened lifespans, and mental decline (Ducharme, 2019). The article further mentions the fact that sleep loss can be linked to negative metabolic changes and increased caloric intake, as well as to impaired performance and productivity (Ducharme, 2019). Dr. Cavanaugh’s research expands on these associations by examining the cellular and molecular mechanisms through which they occur. In his lab, he exposed Drosophila melanogaster to 4 hour phase delays in lighting conditions in order to mimic CCM. When this was done, he observed a 15% reduction in median lifespan of the flies (Boomgarden et al., 2019). In this way, Dr. Cavanaugh directly observed the “shortened lifespans” that the Time magazine article mentioned.
Dr. Cavanaugh went on to discuss his use of RNA sequencing in order to examine how gene expression changes with prolonged misalignment of circadian rhythms using flies that modeled chronic circadian misalignment conditions. In this way, he could identify the molecular changes underlying the physiological consequences of circadian misalignment that were discussed in the Time magazine article, and that were observed through his findings of decreased longevity in CCM flies. After 3 weeks of exposure to either the control or the CCM conditions, Dr. Cavanaugh observed hundreds of genes that were either down- or upregulated relative to what they had started at (Boomgarden, et al., 2019). Furthermore, Dr. Cavanaugh observed that after 2 weeks of CCM exposure, genes involving lipid metabolism were differentially expressed, which suggests that altered lipid metabolism may play a role in the harmful health consequences of circadian misalignment (Boomgarden, et al., 2019). Dr. Cavanaugh also discussed the finding of an upregulation of stress-related genes and a decreased expression of genes involved in developmental processes, which helps to explain a mechanism through which CCM speeds up the rate of organismal decline and processes involved in aging (Boomgarden, et al., 2019). Together, all of the results of the RNA sequencing that Dr. Cavanaugh discussed relate to the health risks of circadian disruption that the Time magazine article discussed by providing potential mechanisms through which they occur.
In the Time article, Dr. Goldstein talks about how taking a nap in the middle of the day is a better solution to sleep loss than sleeping in too late on the weekends. This aligns with Dr. Cavanaugh’s mention of the midday “siesta”, which is a decline in activity around the middle of the day observed in many organisms, including humans. In this way, napping allows one to keep circadian rhythms on track by maintaining a constant waking time on the weekend rather than disrupting these rhythms further by sleeping past one’s normal waking time. The article also discusses the importance of limiting one’s light exposure at night, including looking at phone or computer screens, to prevent light from disrupting one’s circadian rhythms.
The findings of Dr. Cavanaugh’s lab complement the Time magazine article by providing explanations and cellular processes underlying the effects of sleep loss described in the article. Both Dr. Cavanaugh and Dr. Goldstein discuss how circadian rhythms are affected by irregular sleep patterns, and why this makes catching up on lost sleep difficult. Furthermore, both discuss the health consequences that result from chronic circadian misalignment, and Dr. Cavanaugh’s lab specifically uncovers potential mechanisms that account for some of these consequences. These findings suggest molecules and pathways that would be good targets for future studies of circadian misalignment, and both Dr. Cavanaugh and the Time article emphasize why such studies are of utmost importance in today’s society.
Sources:
Boomgarden, A. C., Sagewalker, G. D., Shah, A. C., Haider, S. D., Patel, P., Wheeler, H. E.,... Cavanaugh, D. J. (2019). Chronic circadian misalignment results in reduced longevity and large-scale changes in gene expression in Drosophila. BMC Genomics, 20(1). doi:10.1186/s12864-018-5401-7
Ducharme, J. (2019). Ducharme, J. (2019). Can You Really Catch Up on Lost Sleep? Here's
What the Science Says. Time. Time. Retrieved April 17, 2019, from http://time.com/5541101/how-to-catch-up-on-sleep/
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