For some species, when external conditions become bad, they spontaneously go into hibernation, slowing down their metabolism by lowering their body temperature, as if they were putting their body in "standby" mode.
Although humans do not spontaneously enter this state, there are many animals around us that have this function, such as squirrels and bears.
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Scientists have long been working on the ability to enter a hibernation-like state in humans, a feature that could play a role in specific scenarios, such as treating patients in intensive care units and long-distance space travel.
Mice that "hibernate" with ultrasound
Scientists used therapeutic ultrasound to target deep areas of the mice's brains and successfully put them into a hibernation-like state. However, mice are naturally capable of hibernation, so the researchers tested the technique on rats that couldn't hibernate spontaneously. The research results were published in the journal Nature Metabolism in 2023, which provides a potential possibility and reference for the study of the regulation of brain physiological activities through ultrasound.
New experiments in hibernation. Image source: Reference [1]
The researchers placed helmet-like probes on mice in an attempt to non-invasively induce hibernation-like conditions by stimulating deep brain structures through ultrasound. The team used ultrasounds, which are different frequencies from those used for medical purposes, such as prenatal screening, to target the anterior hypothalamic visual area, which contains neurons that play a role in hibernation, as shown in previous studies.
When these neurons are stimulated by ultrasound, they send signals to brown adipose tissue (highly metabolic adipose tissue located in the upper back) that too low a temperature will raise body temperature, while ultrasound stimulation signals from the foresight area inhibit the activity of brown adipose tissue and prevent body temperature from rising.
To confirm the cooling effect, the researchers used an infrared camera to track the cooling of the skin in the brown fat area and the heat dissipation of the animal's tail. At the same time, they also measured a reduction in oxygen utilization in mice, which again suggests that the mice slowed down their metabolism. In addition to fat cooling and metabolic retardation, the mice also showed other signs that resembled hibernation, such as reduced exercise and decreased heart rate.
The body temperature of the mice in the experiment was reduced. Image source: Reference[1]
However, mice also spontaneously hibernate when they are frightened or stressed. To prove that the drop in temperature in mice was not due to stress or fear factors, the researchers turned their attention to rats that did not have this natural response.
The experimental results showed that the ultrasound signal induced a lower body temperature in the rats, which confirmed that the ultrasound acting on the foresight region was the cause of the hibernation-like state. However, scientists say that rat experiments are only a process of proof-of-concept, and they are still far from practical application.
The researchers used ultrasound stimulation to put the mice in a state of "hibernation" for 24 hours. When the body temperature rises, the ultrasound stimulation is restarted, acting like a regulator to lower the body temperature of the mice; After turning off ultrasound stimulation, the mice quickly returned to normal body temperature and metabolism, and this whole process did not have a significant negative effect on the mice.
For this phenomenon, scientists have found that after delving into cellular responses, ultrasound affects the flow of ions, such as calcium ions, into the foreoptic neurons, triggering signals to reach the brown fat and preventing the animal's body temperature from rising. Sure enough, when the researchers removed the proteins that control the flow of such ions, such as calcium, the effect of ultrasound on lowering body temperature was correspondingly diminished.
Ultrasound causes hypothermia and hypometabolism by activating neurons in POA. Image source: Reference[1]
These results suggest that the protein acts as a "nanoswitch", which is the most important finding of the study. It is not difficult to think that there may be similar proteins in other brain regions that are sensitive to ultrasound.
In contrast to previous studies, to achieve this "hibernation" effect, researchers need to inject the gene of a protein into the target region to activate (light or drug stimulation) the target cells, which is a complex and unsafe process. This new non-invasive method is not only flexible and safe, but also allows the ultrasound stimulation to be adjusted at any time as needed, which has great application potential.
However, experiments using ultrasound to alter brain activity may have ethical implications, especially when it comes to human applications in the future, which will require more research and careful handling.
How long will it take for humans to "hibernate"?
Having said that, if "non-invasive induced hibernation" is achieved in humans, the application space will be wide.
For example, it can be used when a stroke or heart attack patient is in the hospital to be rescued, because these two emergencies can cause the affected tissues to lack oxygen, and the "hibernation" state has a low oxygen requirement, which can delay or prevent physical injury, which will ensure that their lives are not affected until they are admitted to the intensive care unit. Moreover, in the intensive care unit, inducing "hibernation" reduces the dose of medication and monitoring required to care for the patient.
There is also a potential application that may exist, namely interstellar travel in future scenarios, where the "hibernating" state can help humans easily spend long hours in space.
Scientists say the next target would be to test on larger, non-human animals, possibly pigs, because they have no hair, have a similar body temperature to humans, and have the closest data to humans. After that, this technology will gradually be applied to monkeys and humans.
Our exploration of "hibernation" is a long and bright road.
bibliography
[1] Yang, Y., Yuan, J., Field, R.L. 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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