How long will it take for humans to hibernate? Not far away!

For some species, when external conditions become severe, they will spontaneously enter a state of hibernation, slowing down their metabolism by lowering their body temperature, just like switching their body state to "standby" mode.

Although humans do not enter this state spontaneously, there are many animals around us that have this ability, such as squirrels and bears.

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Scientists have long been committed to studying the ability for humans to enter a hibernation-like state. This function may be useful in some specific scenarios, such as the treatment of patients in intensive care units and long-distance space travel scenarios.

Mice hibernated using ultrasound

Scientists used therapeutic ultrasound to target deep areas of the mouse brain, allowing the mice to successfully enter a hibernation-like state. However, mice are born with the ability to hibernate, so the researchers tested the technology on rats that cannot hibernate spontaneously. The research results were published in the journal Nature Metabolism in 2023, which provides potential possibilities and references for the study of regulating brain physiological activities through ultrasound.

New hibernation experiment. Image source: Reference [1]

The researchers placed a helmet-like probe on mice in an attempt to non-invasively induce a hibernation-like state by stimulating deep brain structures with ultrasound. The team chose ultrasound at a different frequency than those used for medical purposes (such as prenatal screening) and targeted the anterior visual area of ​​the hypothalamus (an area that contains neurons that previous studies have shown to play a role in hibernation).

When stimulated by ultrasound, these neurons send signals to brown adipose tissue (highly metabolic adipose tissue located in the upper back), which will increase body temperature if the temperature is too low. The ultrasound stimulation signals from the anterior visual area inhibit the activity of brown adipose tissue and prevent the body temperature from rising.

To confirm the cooling effect, the researchers used infrared cameras to track the cooling of the skin in areas of brown fat and the heat dissipation from the animals' tails. They also measured that the mice reduced their oxygen utilization, again suggesting that the mice slowed down their metabolism. In addition to fat cooling and slow metabolism, the mice also showed other signs of hibernation-like states, such as reduced exercise and lower heart rate.

The body temperature of the mice in the experiment decreased. Image source: Reference [1]

However, mice can also spontaneously enter hibernation when frightened or stressed. To prove that the mice's temperature drop was not due to stress or fear, the researchers turned their attention to rats, which do not have this natural response.

The experimental results showed that the ultrasonic signal induced a lower body temperature in the rats, which confirmed that the effect of ultrasound on the frontal area was the cause of the hibernation-like state. However, scientists said that the rat experiment was only a proof of concept process and was still far from practical application.

The researchers put mice into a 24-hour "hibernation" state through ultrasound stimulation. When the body temperature rises, the ultrasound stimulation will restart, lowering the body temperature of the mice like a regulator; after turning off the ultrasound stimulation, the mice quickly return to normal body temperature and metabolism, and this whole process has no obvious negative effects on the mice.

After studying the cell response in depth, scientists found that ultrasound affects the flow of ions (such as calcium ions) into the preoptic neurons, triggering signals that reach brown fat and prevent the animal's body temperature from rising. Sure enough, after the researchers removed the protein that controls the flow of ions (such as calcium ions), the effect of ultrasound on lowering body temperature was weakened accordingly.

Ultrasound induces hypothermia and hypometabolism by activating neurons in the POA. Image source: Reference [1]

The above results show that this protein is like a "nano switch", which is the most important discovery of this study. From this, it is not difficult to imagine that there may be similar proteins sensitive to ultrasound in other brain areas.

Compared with previous studies, to achieve this "hibernation" effect, researchers need to inject a protein gene into the target area to activate (light or drug stimulation) the target cells, which is a complex experimental process and has low safety. This new non-invasive method is not only flexible in operation and highly safe, but also allows the intensity of ultrasound stimulation to be adjusted at any time as needed, and has great application potential.

However, experiments using ultrasound to change brain activity may involve ethical issues, especially when it comes to future human applications, which will require more research and careful handling.

How long will it take for humans to achieve "hibernation"?

Having said that, if "non-invasive induction of hibernation" can be achieved in humans, it will have a wide range of applications.

For example, it can be applied to the process of patients suffering from stroke or heart disease rushing to the hospital for emergency treatment. Since these two emergency situations will cause hypoxia of the affected tissues, the low oxygen demand of the "hibernation" state can delay or prevent physical damage, which will ensure that their life safety is not affected before entering the intensive care unit. Moreover, in the intensive care unit, inducing "hibernation" will correspondingly reduce the dosage of drugs and monitoring measures required to care for the patients.
Another potential application is interstellar travel in future scenarios. The "hibernation" state can help humans easily spend long time in space.

Scientists said that the next research target should be to test on larger non-human animals, possibly pigs, because they have no hair, body temperature is similar to that of humans, and experimental data is closest to humans. After that, this technology will gradually be applied to monkeys and humans.

Our exploration of achieving "hibernation" is a long but brilliant journey.

References

[1] Yang, Y., Yuan, J., Field, RL et al. Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound. Nat Metab 5, 789–803 (2023).

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