The marvel and risk of hibernation
Genetic and physiological basis of hibernation
Why don’t humans hibernate?
Implications of human hibernation
References
Further reading
Hibernation is an adaptation found in many creatures that helps them survive cold and dark winters when resources are unpredictable or insufficient. During hibernation, many mammals and birds turn down their metabolism to save energy. The hibernating period varies from one species to another.
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The marvel and risk of hibernation
Certain animals hibernate because of insufficient food supplies during winter. Therefore, by going into a long, deep sleep, they avoid this harsh period and wake up when food is more plentiful. Some of the common hibernating animals are bears, hamsters, little brown bats, eastern chipmunks, and some species of ground squirrels. Some insects, amphibians, and reptiles also hibernate.
Typically, hibernators consume extra food in the fall in anticipation of their winter slumber. They store considerable amounts of white and brown body fats before entering hibernation. Brown fat provides extra body heat and energy that is needed when the animal wakes up. Interestingly, some animals also store food in their den for consumption during brief wakeful periods.
Hibernation is generally linked to a significant reduction in core body temperature and metabolic rate to a fraction of basal metabolic rate (BMR). Furthermore, the heart and respiration rates decrease dramatically. To date, the exact physiological definitions of hibernation remain elusive.
Although both hibernation and torpor share many similarities, there are some dissimilarities as well. For instance, hibernation could last for up to nine months, whereas torpor lasts for up to less than twenty-four hours. Sometimes, hibernation can be interrupted, which is known as euthermia, and during this period, animals heat up and move around for several hours.
The mean metabolic rate of hibernation was estimated to be approximately 6% of BMR. After entering hibernation, a significant reduction in energy consumption occurs. For instance, yellow-bellied marmots could save up to 85% of their energy, which enables their survival during winter months.
Two key risk factors of hibernators are that they are exposed to predators and unpredictable climates. Furthermore, hibernators could die from lack of fat and premature awakening.
Genetic and physiological basis of hibernation
Hibernation is controlled by the endocrine system and central nervous system (CNS). The brain is inherently involved with entrance and awakening from hibernation. While entering hibernation, activation of hypothalamic regions occurs along with inhibition of cortical regions.
A mice model revealed that the introduction of 3-Iodothyronamine (T1AM), an endogenous thyronamine, binds to trace amine-associated receptor 1 (TAAR1) and reduces cardiac output and heart rate. Thyroid hormones modulate basal metabolism at different stages of life. These hormones play a vital role in the process of hibernation.
Hibernators are resistant to hypoxia and do not undergo organ damage. They are able to inhibit the apoptotic response in the brain via the regulation of anti-apoptotic proteins. In some cases, ascorbate functions as an anti-oxidation agent that alleviates the increased reactive oxygen species (ROS) levels during arousal from hibernation. In some hibernators, an increased expression of glutathione peroxidase-3 gene is observed. This enzyme has been associated with the detoxification of hydrogen peroxide in plasma.
How does hibernation work? - Sheena Lee Faherty
The hibernating animals also enter an immunosuppressed state to prevent general inflammation in the body. The reduction in blood leucocytes and thrombocytes has been correlated with sphingosine-1-phosphate (S1P) levels in a temperature-dependent manner. During deep hibernation, the body temperature drops along with the S1P level. In contrast, when a hibernating creature awakens, the S1P level increases. The clotting factors FVIII and FIX also reduce significantly during torpor or hibernation, compared to non-hibernating species.
Why don’t humans hibernate?
Typically, most animals that hibernate are small, and during cold weather, they lose the capacity to get adequate food to sustain life. Humans do not hibernate predominantly because their evolutionary ancestors were tropical animals without any history of hibernation. In the last hundred thousand years, humans have only migrated to temperate and sub-arctic latitudes. This time period is not long enough to evolve all metabolic adaptations required to hibernate.
Importantly, humans discovered fire, shelter, clothes, hunting, and agriculture. All these factors contribute to human survival in cold weather. Ancient tribes that tried to sleep through winters were quickly ousted by other tribes with fur clothes and campfires. Additionally, humans being active year-round, the need for hibernation did not come up.
Implications of human hibernation
Since genes associated with hibernation are present in the human genomes, there is a possibility to induce hibernation temporarily using proper molecular techniques. For instance, genes that are upregulated in hibernation can be delivered in humans via viral or non-viral vectors to enhance genetic expression.
Furthermore, small RNA molecules can be delivered to perform gene silencing and achieve downregulation at the transcriptional level. DNA methylation can be used to up or downregulate gene expression.
Many chemical compounds, such as Hydrogen Sulphide (H2S), 5′-adenosine monophosphate, and [D-Ala2, D-Leu5]-enkephalin (DADLE), can induce hibernation or torpor state in non-hibernating animals. These chemicals predominantly function as anti-apoptosis, anti-inflammation, anti-oxidation, or anti-coagulation agents.
If human hibernation were possible, it would be beneficial in certain areas. The induction of a hypometabolic state would aid in the treatment of critical illness as it could reduce the risk of organ damage. For instance, induction of hyperthermia could significantly reduce hypoxia-induced injury that includes brain injury and intestinal ischemia-reperfusion (I/R) injury.
Cryonics is an area of research that is perceived to be an unrealistic technique by most people. This technique is associated with lowering of body temperature of patients who cannot be saved or cured with current technologies. Cryonics is linked to preserving a patient via lowering of temperature until the development of treatments or technologies to revive them and restore their health issues. Most people perceive cryonics to be an unrealistic approach because induction of hypothermia in the human body could cause ischemia and reperfusion injury.
Induction of hibernation in astronauts could positively reduce medical challenges and resource requirements during interstellar space travel. In this context, NASA induced a mild hypometabolic state in selected individuals, and this study reported no detrimental effects for up to fourteen days. This observation indicates the possibility of therapeutic hypothermia in humans.
References
- Hunstiger, M. et al. (2023) Non-shivering thermogenesis is differentially regulated during the hibernation season in Arctic ground squirrels. Frontiers in Physiology. 14, 1207529. https://doi.org/10.3389/fphys.2023.1207529
- Cottier, C. (2023) Could Humans Ever Hibernate in the Future? [Online] Available at: https://www.discovermagazine.com/the-sciences/could-humans-ever-hibernate-in-the-future
- Couzens, D. (2022) What is hibernation, how does it work, and which animals do it? [Online] Available at: https://www.discoverwildlife.com/animal-facts/what-is-hibernation
- Constant, T. et al. (2020) Integrating Mortality Risk and the Adaptiveness of Hibernation. Frontiers in Physiology. 11(706). https://doi.org/10.3389/fphys.2020.00706
- Vaughan, D. (2019) Why Do Some Animals Hibernate?. Encyclopedia Britannica. [Online] Available at: https://www.britannica.com/story/why-do-some-animals-hibernate
- Pan, M. (2018) Hibernation induction in non-hibernating species. Bioscience Horizons: The International Journal of Student Research. 11. https://doi.org/10.1093/biohorizons/hzy002
- Lewy, A. J. et al. (2009) Winter Depression: Integrating mood, circadian rhythms, and the sleep/wake and light/dark cycles into a bio-psycho-social-environmental model. Sleep Medicine Clinics. 4(2), pp. 285–299. https://doi.org/10.1016/j.jsmc.2009.02.003
- Lee, C.C. (2008) Is human hibernation possible? Annual Review of Medicine. 59, pp.177-86. doi: 10.1146/annurev.med.59.061506.110403.
Further Reading
Idiopathic hypersomnia may not be as rare as previously thought