Hibernation-Like State Induced by Ultrasound Could Enable Long-Distance Spaceflights

A new study shows that a hibernation-like state can be induced in mice using ultrasound waves. The study may have ramifications for how humans approach tasks that require low metabolic activity over long periods of time, such as interstellar space travel. The research was published in Nature Metabolism by a team at Washington University in St. Louis.

Sleeping our way to the stars

The dream of long-distance human spaceflight has always faced one significant barrier: humans have pretty short lifespans, galactically speaking. The trip to Neptune, the most distant planet in the solar system, would take 12 years. The space probe Voyager 1, launched in 1977, only entered interstellar space in 2013. To achieve an ambitious mission to the stars, we will require both faster spacecraft and much more resilient and long-lasting humans.

Science fiction has dutifully previewed this goal, showing future astronauts using deep-sleep tubes and hibernation chambers to keep themselves slumbering over long interstellar distances. New research in rodents suggests that the process of sending mammalian bodies into a hibernation-like state might be easier than we first thought.

Time for torpor

While mice don’t hibernate, they do enter a state called torpor in response to low environmental temperatures or decreased food availability. Torpor lasts just a few hours and looks like a deep sleep, where a mouse’s movements decrease, and its body temperature plummets to below 70° F. Researchers have shown previously that torpor can be induced with invasive brain surgery and gene modification. But these invasive approaches are unlikely to be of much use in humans.

The new study has now shown that the same effect can be produced by simply directing ultrasound pulses at mice’s heads. The researchers, who were led by Professor Hong Chen, say this technique is highly controllable and can induce torpor, with no side effects, for up to 24 hours. Excitingly, the researchers were also able to induce torpor in rats, a species that does not normally go into this low-energy state.

Chen’s team delivered ultrasound waves to their animals using a wearable device, which enabled them to freely move around. Short bursts of ultrasound waves were fired off, which caused the animals to enter a torpor-like state just a few minutes later. In this state, mice’s body temperatures fell while their tail temperature increased, which the authors say is indicative of the body releasing excess heat. The mice also consumed less oxygen in this state and had a reduced metabolic rate. Their heart rate also fell by almost half. But just an hour later, the mice recovered from their torpor spontaneously – a key feature of natural torpor that the authors were keen to replicate.

Can torpor be extended?

The authors also wanted to see whether they could extend torpor and used a feedback loop approach to achieve this. Chen’s team created a link between a heat sensor and their ultrasound device, meaning that when the mice’s body temperatures crept back up, indicating they were starting to wake from their torpor, more ultrasound waves would automatically be used to send them back to rest. This process was successfully used to keep the mice in torpor for a 24-hour period, with no ill-effects afterward.

Digging down into the mechanisms behind this ultrasound torpor, the team found that it was kickstarted by activating brain cells in the hypothalamus preoptic area (POA). Ion channels, molecular structures that carry chemicals in and out of cells, had previously been considered critical in this process. The team showed that the channel protein TRPM2 was highly enriched in the neurons that enabled ultrasound torpor. Mice genetically bred to not have this channel were substantially less affected by the ultrasound.

Fat and rats

The researchers went on to examine other areas of the brain and body that contributed to the torpor, detailing that other regions of the hypothalamus, a small brain area that regulates metabolism and some hormonal release, were involved. In the rest of the body, the team identified that brown fat tissue helped to induce torpor by reducing tissue temperature. A final experiment in rats showed that torpor could be stimulated even in animals that don’t normally undergo it. The rats showed smaller drops in body temperature than mice did, but the researchers regard this as an important first step in potentially translating their rodent findings to other mammal species.

As ultrasound stimulation has previously been shown to alter processes in the human brain, the researchers write that their technique has “excellent promise for translating to humans”, although “much work needs to be conducted” before we can sardine-pack our would-be astronauts using an ultrasound musical score.

“What may seem like one small step for this one research group,” said Martin Jastroch and Frank van Breukelen, researchers at Stockholm University and the University of Nevada who were not involved with the research, “promises to be a giant leap for mankind to exploit torpor-like states in medicine and possibly for deep-space travel.”

Reference: Yang Y, Yuan J, Field RL et al. Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound. Nat. Metab. 2023. doi: 10.1038/s42255-023-00804-z