Hibernating humans

By Themis Halka

Humans can’t hibernate – yet. Hibernation is a mechanism that evolved in numerous species, presenting clear advantages in terms of energy conservation.¹ Winter hibernation, whilst naturally occurring in various animals, is not a desirable option for humans. However, being able to artificially enter hibernation could present great opportunities, particularly for clinical applications and space travel. 

Numerous species (including some mammals) can naturally enter torpor – this is a state of reduced metabolism characterised by decreased heart and respiration rates, and a fall in body temperature.² Two types of torpor can be defined. Shallow daily torpor follows the circadian rhythm of activity and rest. In mammals, it is associated with a 0.5-2°C fall in body temperature, as well as a decrease in metabolic rate of up to 20%. Longer-lasting torpor of more than 24 hours is described as hibernation, in which the decrease in body temperature and metabolism rate is usually more pronounced.³ Great variations in the duration of torpor and decrease in temperature exist amongst different species. 

As opposed to various other mammals, humans appear to be unable to naturally enter torpor. However, the evolutionary origins of humans do not exclude the potential to enter torpor, as shown by the hibernating ability of various mammals. Large mammals like bears, and some primates like the fat-tailed dwarf lemur of Madagascar, can hibernate, suggesting that in theory, humans are not too big or energy-hungry to enter torpor.²

Making humans enter hibernation on a yearly basis is not an aim of the scientific community. However, understanding the underlying factors triggering hibernation could be helpful in other domains. Clinically, in several conditions, treatment and recovery could be facilitated if metabolism could be slowed down. In cardiac surgeries, particularly in the case of strokes, poor oxygen delivery to tissues often leads to permanent damage, and perhaps death. In a hypometabolic state, tissues would be protected from damage to some extent due to the lowered oxygen requirements.⁴ Key studies in this field are focusing on the ability of hibernating animals to retain an undamaged nervous system to reduce tissue damage caused by ischemic strokes.⁴ Several of these studies have evidenced a reduction of inflammation, oedema, and intracranial pressure in ischemic rats when shifted into hypometabolic state. 

Inducing short-term torpor in humans is therefore of particular interest to many clinicians. Achieving this short-term torpor has been approached in various ways. One route of lowering human metabolism for clinical purposes is by lowering the body temperature. The simplest and most cost-effective solution, whole-body surface cooling, consists of using cooling blankets and ice packs on the patient.⁵ Other methods have been developed to speed up the cooling time – for example, whole-body endovascular cooling, which consists of inserting a cold saline solution into a patient’s large vein via a catheter.⁵ Inducing torpor using drugs is also an active research field, and numerous molecules are being investigated. For instance, the body-cooling and sedative effects of phenothiazine drugs, which are used for treating schizophrenia, are under investigation.⁵ The benefit of hypothermia on stroke treatment remains uncertain – however, there is suggestion that hypothermia could provide avenues to reduce permanent damage to crucial organs like the brain. We must keep in mind that whilst inducing hypothermia might be beneficial to reduce metabolism, non-hibernating animals can only safely bear mild hypothermia of 32-34°C. Inducing severe hypothermia, with a body temperature lower than 28°C, would likely result in cardiac arrest.⁶ 

Recent research also focuses on identifying natural biomolecules whose expression can be altered to induce hypometabolism. A study conducted on mice identified a gene, called procolipase, that could be involved in inducing torpor. Adenosine 5’-monophosphate was found to act as a circulatory regulator to impact procolipase expression in peripheral organs, and so might constitute a target for inducing synthetic torpor.⁷

These results seem promising in efforts to induce transient torpor and reduced metabolism. However, other sectors such as space travel aim to maintain this reduction in the long-term, while still maintaining viability. This remains challenging, as the effects of long-term hypometabolism on non-hibernators is still very unclear. The possibility of hibernating for space travel recalls numerous science fiction movies and would indeed have many benefits regarding preservation of resources and biological function during long space journeys. It also seems that synthetic torpor could help to resist radiation exposure, a possible concern of long space travels.⁸ However, many uncertainties remain, and stem cells are a major concern. Vital for tissue and cell regeneration, the effect of long-lasting torpor on their proliferation, differentiation and self-renewal capacities are unknown. It was suggested that a shift in glial cell action might result in hematopoietic stem cells being recruited into the cell cycle and losing their stemness. This might result in anaemia at the end of hibernation. Bone remodelling, a very energy consuming process, might also be impacted – leading to bone loss during long-term torpor. 

The effects of hibernation on brain function are also being investigated. It has been observed that hibernating animals tend to regularly come out of torpor for periods of hours or days, during which time they regain their normal body temperature before going back to deep torpor.⁴ Interestingly, when out of torpor, animals spend most of their time sleeping, which led scientists to suggest that torpor might disrupt sleep regulation, resulting in sleep-deprivation in animals if maintained into torpor for too long.⁹

In sum, synthetic torpor could be a revolutionary advance for fields from medicine to space travel. At this time, our understanding of torpor mechanisms and its long-term effects remains superficial – but active research is being conducted to better comprehend and control this mechanism that already shows great promise.

References:

1. Lee C.C. Is human hibernation possible? Annu Rev Med. 2008; 59: 177-86. doi: 10.1146/annurev.med.59.061506.110403.
2. Vyazovskiy V. Could humans hibernate? | University of Oxford. 2016. Available from: https://www.ox.ac.uk/research/could-humans-hibernate-0  [Accessed 11 December 2021]
3. Geiser F. Hibernation. Curr. Biol. 2013; 23: R188–193.
4. Forreider B, Pozivilko D, Kawaji Q, Geng X, Ding Y. Hibernation-like neuroprotection in stroke by attenuating brain metabolic dysfunction. Prog Neurobiol. 2017; 157: 174-187. doi: 10.1016/j.pneurobio.2016.03.002.
5. Ban T.A. Fifty years of chlorpromazine: a historical perspective. Neuropsychiatr.Dis. Treat. 2017; 3: 495–500.
6. Moon P.F., Ilkiw J.E. Surface-induced hypothermia in dogs: 19 cases (1987–1989). J. Am. Vet. Med. Assoc.1993; 202: 437–44.
7. Zhang J., Kaasik K., Blackburn M.R., et al. Constant darkness is a circadian metabolic signal in mammals. Nature. 2006; 439: 340–43. 
8. Puspitasari A., Cerri M., Takahashi A., Yoshida Y., Hanamura K., Tinganelli W. Hibernation as a Tool for Radiation Protection in Space Exploration. Life (Basel). 2021; 11(1): 54. doi: 10.3390/life11010054.
9. Trachsel L., Edgar D.M., Heller H.C. Are ground squirrels sleep-deprived during hibernation? American Journal of Physiology. 1991. Available at: https://journals.physiology.org/doi/abs/10.1152/ajpregu.1991.260.6.R1123 [Accessed 12 Nov 2021]