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Sleep Deprivation & Mitochondrial Impacts

Woman sleeping on white sheets

I've always envied people who sleep easily. Their brains must be cleaner, the floorboards of the skull well swept, all the little monsters closed up in a steamer trunk at the foot of the bed.

David Benioff City of Thieves

Sleep deprivation is so commonplace in modern society, it almost seems as if the very act of sleeping has become frivolous — something only a privileged few have access to or time for. The most recent statistics show that 40% of Americans get less than the recommended seven hours of sleep per night,1 with people living in the United States and Japan reporting the least amount of sleep globally.2 People age 65 and older reportedly get the most sleep, but sleep amount decreases with each younger age group, and nearly half of 18- to 29-year-olds get less than the recommended amount.1

Fatigue isn’t the only consequence of a poor night’s sleep. Adults who are short sleepers (less than seven hours) are more likely to report 10 chronic health conditions, including depression, arthritis, diabetes, and asthma.3 Over the past 10 years, researchers have begun to examine what happens at a cellular level when the body is deprived of sleep. Some studies suggest a connection between limited sleep and oxidative stress, pointing to mitochondria as a possible target of the physiological effects of sleep deprivation.4,5

Mitochondria, the cellular source of energy production, play an important role in cellular energy metabolism and homeostasis via generation of several metabolites, including ATP. Acute and chronic stressors influence various aspects of mitochondrial biology, and chronic stress exposure can lead to molecular and functional recalibrations among mitochondria.6 Recent discoveries suggest a role for mitochondria at two levels: as a target of stress and as a mediator of stress pathophysiology,6 suggesting that one of the biological functions of sleep may be to protect against oxidative stress.5-7

In the following IFM video, sleep specialist Jose Colon, MD, MPH, talks about some of the therapies he uses to help patients adopt healthier sleep patterns.

Dr. Jose Colon, MD, MPH, is a sleep medicine specialist (psychiatry & neurology) in Fort Myers, FL, and has been practicing for 16 years.

Over the years, a growing body of evidence has emerged suggesting that energy metabolism and cellular antioxidant mechanisms defending against oxidative damage are coordinated by the circadian clock, the mechanism that keeps bodies attuned to the day/night cycle.8 In 2018, a study using a combination of in-vitro and in-vivo models of human skin fibroblasts and mice established a molecular link between circadian control of mitochondrial morphology and oxidative metabolism. “These could have multiple implications in the context of metabolic homeostasis, with respect to both human health and disease, and with respect to impairment in circadian clock and/or mitochondrial function,” writes Karen Schmitt et al. in Cell Metabolism.

Perturbations in the clock might even be a key initiating factor for diseases linked to compromised mitochondrial function, including neurodegenerative disorders such as Alzheimer’s disease.8

In 2018, researchers used the fruit fly Drosophila melanogaster (which shares many key characteristics with mammalian sleep) to measure how mitochondria function under sleep deprivation.4 By exposing the flies to constant light, researchers were able to alter sleep patterns, causing locomotor deficits, increasing reactive oxygen species production and lipid peroxidation, and affecting mitochondrial activity, antioxidant defense enzymes, and caspase activity.4 Analysis showed that sleep deprivation affected mitochondrial bioenergetics capacity, decreasing respiration at oxidative phosphorylation.4 Work in fruit flies has shown that sleep deprivation can also augment the immune response.7

The first-ever study to analyze the combined effect of physical exercise and sleep deprivation on oxidative stress in humans was conducted in 2018.9 The groundbreaking research suggests that oxidative stress was likely to be a consequence of exposure to not only physical but also psychological stressors related to, among other things, sleep deprivation. The 36-hour survival training in young, healthy men with sleep deprivation showed impaired enzymatic antioxidant defense, increased lipid peroxidation, and muscle damage.9

Clearly, sleep is a physiological necessity, and being deprived of it has many deleterious health effects. How can clinicians help their patients get more rest and limit the maladaptive mitochondrial changes that occur during states of stress? Certain nutrients, including omega-3 fatty acids, antioxidants (including vitamin C and zinc), members of the vitamin B family (including vitamin B12 and folic acid), and magnesium have been shown to protect against oxidative damage to the mitochondria.5

A 2019 systematic review and meta-analysis of 49 studies covering 4,506 participants found that mind-body therapies like meditation, tai chi, qigong, and yoga can be effective in treating insomnia and improving sleep quality for both healthy individuals and patients.10 The therapies resulted in statistically significant improvement in sleep quality and reduction in insomnia severity. Of note, the researchers found that qigong had a slight advantage over tai chi in the improvement of sleep quality.10

For many, sleep is the cornerstone for leading a healthy, joyous life, and yet sleep often goes unaddressed. Screening for sleep disorders is encouraged as a regular practice of Functional Medicine, and there are a range of effective lifestyle interventions for the patient suffering from poor sleep. To learn more, please visit the following IFM resources:

Learn More About Mitochondrial Function

References

  1. Jones JM. In U.S., 40% get less than recommended amount of sleep. Gallup. Published December 19, 2013. Accessed June 10, 2019. https://news.gallup.com/poll/166553/less-recommended-amount-sleep.aspx
  2. National Sleep Foundation 2013 International Bedroom Poll first to explore sleep differences among six countries. National Sleep Foundation. Published September 3, 2013. Accessed June 5, 2019. https://www.sleepfoundation.org/press-release/national-sleep-foundation-2013-international-bedroom-poll-first-explore-sleep
  3. Sleep and sleep disorders: data & statistics. Centers for Disease Control and Prevention. Published May 2, 2017. Accessed June 5, 2019. https://www.cdc.gov/sleep/data_statistics.html
  4. Rodrigues NR, Macedo GE, Martins IK, et al. Short-term sleep deprivation with exposure to nocturnal light alters mitochondrial bioenergetics in Drosophila. Free Radic Biol Med. 2018;120:395-406. doi:10.1016/j.freeradbiomed.2018.04.549
  5. Du J, Zhu M, Bao H, et al. The role of nutrients in protecting mitochondrial function and neurotransmitter signaling: implications for the treatment of depression, PTSD, and suicidal behaviors. Crit Rev Food Sci Nutr. 2016;56(15):2560-2578. doi:10.1080/10408398.2013.876960
  6. Picard M, McEwen BS. Psychological stress and mitochondria: a systematic review. Psychosom Med. 2018;80(2):141-153. doi:10.1097/PSY.0000000000000545
  7. Hill VM, O’Connor RM, Sissoko GB, et al. A bidirectional relationship between sleep and oxidative stress in Drosophila. PLoS Biol. 2018;16(7):e2005206. doi:10.1371/journal.pbio.2005206
  8. Schmitt K, Grimm A, Dallmann R, et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metab. 2018;27(3):657-666.e5. doi:10.1016/j.cmet.2018.01.011
  9. Jówko E, Ró?a?ski P, Tomczak A. Effects of a 36-h survival training with sleep deprivation on oxidative stress and muscle damage biomarkers in young healthy men. Int J Environ Res Public Health. 2018;15(10):E2066. doi:10.3390/ijerph15102066
  10. Wang X, Li P, Pan C, Dai L, Wu Y, Deng Y. The effect of mind-body therapies on insomnia: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2019;2019:9359807. doi:10.1155/2019/9359807

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