Hibernation: The first astronaut tests are closer than we think

Hibernation

Hibernation, a long, deep sleep in which vital functions are reduced to a minimum and from which it is then possible to wake up, years later, in the same starting conditions: it is difficult to find a science fiction film or novel in which protagonists, to face long space journeys, are not subjected to a similar process. These seem improbable prospects, but in this case the fantasy is not so far from reality: for many years, in fact, space agencies have been studying strategies to generate in astronauts a state of metabolic suppression below any known physiological limit, which takes hibernation name. In fact, with new technologies advancing, space exploration directed towards Mars and plans to build a permanent base on the Moon, “human beings will have to deal with dangerous conditions in Space, such as solar radiation, the effects of microgravity on organs, deconditioning, as well as various psychophysiological challenges ”, writes a group of researchers from the European Space Agency (ESA) in a recent article that explores its approach to hibernation.

For these reasons, hibernation , a process which, in addition to being present in films such as  Alien and Interstellar , is typical of many mammals that cyclically suspend their metabolism, could be the key to human exploration of the solar system and to overcome the challenges astronauts face in space. According to experts, one shouldn't wait too long for the first tests on humans: Jennifer Ngo-Anh, ESA researcher and co-author of the study on the space agency's approach to human hibernation told Space.com that, in depending on the availability of funds, the first trials could take place as early as ten years from now. We asked Matteo Cerri, a neurophysiologist who is an expert on hibernation, associate professor at the University of Bologna and coordinator of the hibernation research group for ESA, what it is about, what the advantages would be for humans and what to expect from future .

What is hibernation

It is good to make a premise, because hibernation is often confused with cryonics (also called cryopreservation or cryopreservation), the process – of dubious scientific foundation - which aims to preserve the bodies of deceased people at very low temperatures, waiting for medicine and technology to be able to bring them back to life. In reality, the hibernation studied by scientists does not involve any of this: it is, in fact, a  natural phenomenon , decidedly more akin to mammals such as bears, dormice and bats than to science fiction tropes.

“ With the term hibernation identifies what we more commonly know in Italian as lethargy: a condition in which some mammals are able to enter when they find themselves in a situation of lack of resources ” Cerri affirms to sportsgaming.win Italia. In fact, they are able to switch off their metabolism, to reduce it to a minimum, in a kind of standby in which only the essential vital functions are maintained. These animals are still alive, but consume very little energy: they are thus able to survive a long period of many months without eating, without drinking and without producing biological waste".

Going into more technical details, this particular standby condition , as can also be read in an article by the Italian researcher, is called torpor , a natural, active, reversible and transitory state of metabolism suppression , the which can undergo a reduction - depending on the case - ranging from 60% to 95% compared to normal life, to cope with a particularly hostile environment. The fundamental purpose of torpor, in fact, is to induce a reduction in metabolic rate that allows animals to survive for a long time in adverse environmental conditions, without access to food or water. In nature this phenomenon, widely diffused among numerous vertebrates such as birds, amphibians, reptiles, mammals and also in some primates (such as lemurs), is very variable: the torpor, in fact, can last for a few hours and occur daily, or it can part of more complex behaviors such as hibernation , which, by definition, is a sequence of torpor episodes lasting from 5 to 20 days, separated by periodic awakenings of about 24 hours.

Despite the differences between species and species, the least common denominator of torpor is a drastic change in the physiology of the organism of the animals that encounter it. During torpor, in fact, most of the vital functions are reduced, such as heart rate and ventilation, the body temperature is lowered and many processes that normally take place inside the cells are suspended. “Cells in general stop replicating. This applies to all cells that reproduce, such as hematopoietic cells, stem cells and even cancer cells, which obviously do not die, but are somehow overwhelmed by this wave of energy savings ”, adds Cerri. And again, the immune system undergoes substantial changes, continues the researcher, reaching a sort of state of quiescence, which however does not seem to expose the animal to a greater risk of infections. Not only that: “the brain changes significantly: for example, about 50% of the synapses, the connections between neurons and in fact the area where the brain consumes the most energy, are reabsorbed; neurons communicate less, especially in areas of the brain such as the hippocampus ”. The gastrointestinal system, the composition of the microbiota, the endocrine structure change: in short, the whole organism changes to adapt to this very particular condition.

Offering solutions to astronauts

In particular , among the physiological changes caused by torpor, there are some that could have interesting applications and solve many of the problems that afflict astronauts today, and which are therefore the subject of numerous research by space agencies. In fact, as reported in a recent article , there are two main concerns for the health of astronauts in space, especially on very long missions: radiation and microgravity. Our bodies, in fact, have evolved to live in the earth's environment: we are subject to gravity and the earth's magnetic field protects us from cosmic rays and charged particles that permeate space, which are potentially able, among other things, to cause cognitive deficits and increase the risk of developing tumors; during space missions these conditions fail, exposing astronauts to numerous health risks.

And yet, both obstacles could be overcome by hibernation. “ Among the most interesting adaptations of the body for space missions ”, says Cerri, “ there are those involving the muscles, which do not lose tone, and the bones, which do not show a lack of calcium, despite the long period of inactivity due to torpor. Animals need this because when they wake up from hibernation they need to be ready to move; on the other hand, in humans a few weeks of inactivity is enough to undergo muscle atrophy from disuse ”. This is what also happens to astronauts, because the microgravity condition removes the constant stimulus of gravity from the muscles, reducing their tone, as well as affecting the cardiovascular function, weakening the bones, causing their loss of calcium, reducing kidney function and compromising the immune system. “ An important line of research, therefore, wants to understand what are the molecular aspects, in hibernating animals, which allow the muscles to remain toned despite inactivity ”.

Even more interesting are the applications of research on 'hibernation on radiation protection, because, while there seem to be plausible strategies for the difficulties associated with weightlessness, it is not yet clear how to address this problem, as different solutions have been proposed over time, such as passive shielding systems for spacecraft would be impractical and too expensive. However, hibernation could offer a possible solution: the cells of animals subjected to torpor show a remarkable resistance to radiation damage. “ More than preventing the damage, these cells are very effective in repairing it: it seems that it takes longer than normal cells, but at the end of the process, they show much higher survival rates. This is why we hope to find some drug target that can activate these processes ”, adds Cerri.

Other possibilities

In addition to these advantages, space missions could benefit from 'hibernation from an economic point of view, because smaller spaceships could be built, which do not have to carry the water and food necessary for a long journey, and with less sophisticated filtration systems, as there would be no biological waste.

“Furthermore, there would be numerous advantages for the astronauts, even at a psychological level, as the forced confinement and lack of privacy typical of a space mission can be heavy to bear for such long times”, underlines the researcher.

Looking away from Space for a moment, the research on torpor could also have numerous applications in medicine: for example, inducing hibernation in patients on the waiting list for organ transplants would increase the chances of be able to find a compatible organ. Similarly, hibernation would benefit all those conditions or diseases that could be better treated thanks to a slowdown and dilation of biological time: myocardial infarction, stroke, septic shock, tumors and some types of diseases neurological.

How to induce hibernation

In short, there could be many advantages deriving from hibernation. But human beings are not animals that naturally hibernate: this is why researchers are studying  how to induce torpor artificially, looking for strategies - above all from a pharmacological point of view, but also with physical methods, such as the use of convergent beam ultrasound - which can generate this process in animal models that are unable to hibernate naturally. For example, in 2013 Cerri was the first to hibernate a rat (a non-hibernating animal) in the laboratory: the research group demonstrated that, by pharmacologically inhibiting certain neurons that had a key role in thermoregulation and defense against cold, it was possible to induce a similar to natural numbness.

“ We have only inhibited a small area of ​​the brain, which is able to act as a kind of switch that controls the metabolism and therefore its switching off. It is as if the brain tells the rest of the body not to consume any more energy, and therefore a condition very similar to natural torpor is triggered ”, comments the researcher.

Over the years, there have been other proposals, including the administration of a series of molecules derived from adenosine (which, however, show various side effects, especially at the cardiovascular level), the administration of a mix of different drugs , including xenon and beta blockers, enclosed in a vesicle capable of reaching the brain. More recently, a group of Japanese researchers has shown that a neuronal circuit in the hypothalamus of rodents would be capable of inducing a long-lasting hypothermic and hypometabolic state, very similar to natural torpor.

Joining forces

“ The next step – underlines Cerri – would be to be able to consolidate a technique in order to then be able to evaluate an initial use in the clinic. From that point on we will be able to know if these discoveries are applicable to humans ”.

Once the first trials begin, hibernation applied to space exploration would be a little closer. Speaking of times, even according to the Italian researcher, ten years is a reasonable prospect for the first tests on humans. “ It is mainly a matter of funds and human resources. Right now, the way this kind of research is funded is institutional: researchers write research projects that governments or other entities fund or don't; therefore, there is a dynamic where each laboratory is in competition with the other. If, on the other hand, there was the will to reach the goal faster, therefore to join forces instead of separating them, with the right funding behind it, it would take even less to get to the first tests and understand if human hibernation is something that can be can actually do . After that no one can guarantee, even in the face of a solid rationale, that something works in the life sciences, there is too much variability, but we are optimistic", concludes the researcher.