Zoe Beketova, Contributing Photographer

Improved organ transplantation, enhanced anorexia treatments and even the possibility of sending people deeper into space — Yale researchers believe that studying animals’ natural processes, like hibernation, can help reach these far-reaching results.

“We need to go back to nature and look at the naturalistic,” Elena Gracheva, Yale professor of cellular molecular physiology and neuroscience, said. “With this approach, we can understand not only the biology of specific species, we also can uncover pathways that are directly related to us.”

Hibernation is an intricate process where an animal’s body shuts down almost completely in the winter and reactivates in the spring. The main process behind hibernation is a decrease in the animal’s metabolic rate, meaning their heart and breathing rates, as well as body temperature, drop steeply.

During hibernation season, sleeping animals do not eat or drink anything. They enter a state of “torpor,” where the body shuts down almost entirely.

“Torpor is not sleep,” Rafael Dai Pra GRD ’25, a final year doctoral student in cellular and molecular physiology, said. “The animal is really in survival mode, trying to save as much energy as they can. It’s way more complex than just dropping body temperature.”

Dai Pra believes that hibernation is particularly interesting in thirteen-lined ground squirrels, a close relative of chipmunks.

During hibernation, this species wakes up for interbout arousal periods or IBAs. These are quick, transient periods of awakeness that last 24 to 48 hours. During IBAs, squirrels’ physiological functions are restored, including normal body temperature, but their desire for food and water remains suppressed, Dai Pra explained.

The reason for IBAs is not fully known, but Dai Pra’s research suggests that they help male juvenile ground squirrels undergo puberty and adult squirrels become ready to reproduce in the spring by building up their testosterone levels.

“When you have high testosterone, you start prioritizing lean mass conservation versus fat mass, so it’s harder for these animals to gain weight very, very fast,” Dai Pra said.

After spring mating season, their testosterone levels decrease, allowing the squirrels to accumulate fat to sustain themselves during hibernation. Then, during torpor, testosterone builds up again, preparing them to reproduce again once they wake up.

Essentially, thirteen-lined ground squirrels appear to go through a puberty-esque process every hibernation period.

Shade Eleazer GRD ’28, a third-year student in Yale’s Interdepartmental Neuroscience program, has found that female ground squirrels also seem to use hibernation to become reproductively fertile.

Hibernation, for thirteen-lined ground squirrels, appears important in fertility, hunger management and temperature control. Understanding this could open insights into human physiology and medicine.

Research stakes for human medicine

The torpor of thirteen-lined ground squirrels is unique. Their pulse drops to just a few beats per minute, down from their usual 250, and their body temperature plummets to around four degrees Celsius. Other hibernating animals cannot drop their body temperature this low, even during torpor.

The key point here is that these processes are not only unique but reversible.

“Once the squirrels emerge from hibernation, they’re eating, they’re moving,” Dai Pra said. “They seem to be okay.”

Studying the body temperature drop these squirrels experience and how they safely reverse it could improve human surgery and organ transplantations.

Rebecca Greenberg GRD ’25, a sixth-year PhD student in the lab, works on understanding how thirteen-lined ground squirrels can still feel touch even when their bodies drop to four degrees Celsius. Human nerves cannot process touch signals at such temperatures and can even die.

Many surgeries require patients to have their bodies cool down, which leads to the loss of certain nerves and tissues, Greenberg explained. Studying squirrels could improve the understanding of cellular mechanisms for adaptation and applying it to different tissues.

Another implication of this research is in the field of physiological anorexia, where elderly patients struggle with their appetite. Gracheva explained that this condition is often hard to treat and targeted medication is needed.

Gracheva believes that harnessing the hunger control mechanisms of hibernation could be invaluable to physiological anorexia research. The answer could lie in the hormone T3. 

When animals hibernate, T3 levels are much lower in the brain than usual. This essentially shuts off the brain regions responsible for hunger until they wake up, Gracheva said. Understanding how to control T3 levels in humans may function as a treatment for physiological anorexia, improving patients’ appetites.

A final possible application of this research is space-related. Placing astronauts into a state of hibernation, or even just reducing their body temperature by a few percent, could decrease the amount of food and water needed on board the aircraft, said Gracheva. This would make the aircraft lighter, faster, and, in turn, able to travel further.

Research in this field is ongoing. 

According to Dai Pra, the tools for studying squirrels are not quite as developed as those for studying mice or other, more common animal models in science. 

This field is also difficult to replicate in other species due to the counter-regulatory mechanisms that bring body temperature back up. For example, hibernating mice and rats only drop their body temperature to 20 to 25 degrees, unlike the four degrees of ground squirrels.

Understanding how thirteen-lined ground squirrels maintain their health and increase their fertility during hibernation could unlock the secrets of human medicine and physiology.

Ground squirrels hibernate for between six and eight months.