I promised to get back to the article that Saikishan pointed me to. It occurs to me given the debate that was going on that Saikishan must have simply typed in “is human hibernation possible?” into google and sent us the first scholarly article link that popped up! Regardless, the research is interesting, even if the title has more hype than necessary. The article is from the Annual Review of Medicine, and has been written by Cheng Chi Lee from the U. Texas.
Some mammals like bears are known to hibernate over winter, while others like hamsters or mice are known to go into a circadian state of torpor (circadian meaning ‘daily’; they showed this by ablating the suprachiasmatic nucleus which is known to control the circadian clock and finding that the torpor state is correspondingly disrupted). The difference between torpor and hibernation seems to be one of degree, says the author. The present article deals with the chemistry behind this transition from activity to torpor. Two compounds, 2-deoxyglucose and hydrogen sulphide are already known to induce a state of torpor in animals. The article finds that a third compound called 5′-adenosine monophosphate (if you know what ATP is, you get to AMP by taking away two ‘P’s – phosphate groups) can also be used. 5’-AMP is – or was, the article was written in 2008 and I haven’t checked for newer research – the only naturally occurring compound that can do this that we know of (or, as appropriate, knew of).
The first of the three compounds, 2-deoxygenase induces torpor by inhibiting glycolysis – stopping glucose from being utilised. Under administration, hamsters readily go into torpor even when they are in proper light. The second compound, H2S, was found to bring the body temperature of mice down to 15 C and a state of suspended animation for up to six hours. The precise mechanisms behind the effects these compounds have on mice and hamsters are as yet unknown. However, they both work by stopping production of ATP – 2-deoxygenase does this by stopping glucose from being oxidised to ATP and NADH (outside mitochondria, if that means anything to you), whereas H2S disrupts the oxidation inside mitochondria (by inhitibing cytochrome C, again if that means anything to you). Decreased ATP production and consumption are observed in all hibernating behaviour.
If this can happen with mice and hamsters, could other mammals too have retained similar biochemistry? We know that organs can be stored for several hours on ice, be transplanted into patients, and return to normal functioning. There are also cases of where people have been stuck in extreme cold and gone into hypothermia without dying, and even recovering full bodily function. The author deduces from this that non-hibernators’ organs are capable of withstanding extreme hypoxic stress if their metabolic demands are reduced. I should point out that both mice and hamsters do have natural torpor states. So, given that the difference between hibernation and torpor is one of degree, calling mice ‘non-hibernating mammals’ seems like stretching it.
Hibernation necessarily requires a dark environment. The author reports that using a gene analysis, a link was discovered between the circadian light-dark cycle and something called procolipase (‘lip-ase’ means something along the lines of ‘breakdown lipids’) which is only expressed in the liver and the pancreas, that procolipase was activated in peripheral organs in mice that were kept in the dark, and that the expression of procolipase was shut down in various organs when the animals were exposed to light. The only way a whole-body response like that could take place is if the circulatory system is involved, and if the molecule behind all this were a circulatory molecule with a circadian profile. The researchers found the 5′-AMP molecule to fit the bill, as it were.
5′-AMP works by inducing the procolipase gene expression, but with a time-lag, suggesting that this is an indirect process. 5′-AMP causes severe hypothermia in mice (body temperature of 25 C as opposed to 37C normally), and a severe reduction in heart-rate. 5′-AMP must, suggests the author, inhibit the natural thermoregulation of the body, causing core body temperature to drop and metabolism to slow down. It has been shown to also play a role in the regular torpor states of mice. However, what core temperature can be reached safely depends on what animal we’re talking about. Usually, the larger the animal, the smaller the reduction in temperature from 37C.
I will say nothing more here of the mechanism the author proposes for the effect of 5′-AMP; I don’t understand much of it. What is clear, however, is that this research has found a natural molecule that plays a role in torpor induction, and if it is true that other mammals have similar biochemical pathways as the mice, this molecule could be used to induce hypothermia and save lives in clinical applications (trauma, heart attacks, strokes, and other major surgeries). What this must tell you, however, is that none of this is a reason to go ‘oh, wow, human hibernation!’. We can already induce hypothermia in patients to save their organs. This is now done by literally putting the patient on ice, which is an inefficient way of doing it. A chemical hypothermia-inducing agent would be better.
Lee, C. (2008). Is Human Hibernation Possible? Annual Review of Medicine, 59 (1), 177-186 DOI: 10.1146/annurev.med.59.061506.110403