Welcome to Chasing Life. Hibernation. We've all heard the term and might even think we know what it means. Bears and squirrels, other animals, hunkering down for the winter, only to emerge when the warmer weather of spring arrives. But what if hibernation itself was more complicated than we realized? His heart rate will go from about 3 beats a minute to upwards of 400 beats per minute. Wow. In about 10 minutes. That's incredible. And what if hibernators had superpowers that could one day be tapped for humans, for things like cancer, heart attacks, depression, and even space travel? Those are the questions researchers and scientists all over the world are getting closer to answering every day. I'm Dr. Sanjay Gupta, and this is Chasing Life. Christopher Gregg is a professor of neurobiology and human genomics at the University of Utah. Do you want any fruit? No thanks. But his work on human genes has led him to a completely different type of mammal, hibernators. We were trying to crack the code on the genome to find these switches that control our genes. Our idea was that we could compare the genomes of species with a particular trait against species that didn't have that trait. And we were excited about traits that were to do with behavior, metabolic control. And as we went through all of the superpowers that have evolved, hibernation just jumped out at us. Hibernation in its simplest form is not sleep. Instead, it's a length of time when an animal's metabolic activity drops dramatically. That state of lowered metabolic activity is called torpor, and most hibernators cycle in and out of that throughout hibernation. When that happens, body temperature can drop to the point of freezing. Heartbeat, respiration, and blood flow all slow. Parts of the brain shut down, and the aging process itself grinds to a halt. In essence, it's a full-body shutdown to conserve energy. In 2016, researchers in Gregg's lab were able to isolate and compare specific parts of the genome of hibernators to the human genome. And in doing so, they made a discovery. Hibernators are changing how these genes behave. And we found the specific regulatory elements that we think are important for doing that. Now, think of the human genome as a house. In the house, there are light switches with corresponding lights. Your genes are those light switches. They contain instructions on how to build, maintain, and run your body. We share many of these light switches or genes with most hibernators. The key difference is that hibernators have developed ways to turn those shared light switches on and off. This is a very cool data set. I have to see. I see what you mean by the strength of the signal. Armed with this knowledge, the lab's research is now being applied in the fight against cancer. Most people think of hibernators, they think of the gaining of all the body fat and then the losing. Lesser known is that when hibernators have cancer, the cancer stops growing when they are in torpor. It stopped spreading, what they call metastasizing. How have you been? Mostly pretty good. This time, his work is personal. Show you the tumor markers. Yeah. So this is the first time they've consistently both gone down. I have a rare form of cancer, a male breast cancer. I was diagnosed in 2018 with stage 4 disease, so it's advanced. That's unfortunately a terminal diagnosis. Since early 2025, he's been working alongside researchers Alana Welm and K.T. Varley. They're at the Huntsman Cancer Institute in Utah. And their goal is to figure out why cancer cells go dormant, how they stay dormant, and then what reactivates them. We have known for decades that cancer cells can be in the body in an undetectable state from old autopsy studies. Starting in 2022, the multi-year research program called The Trance Project launched a rapid autopsy program to study these invisible dormant cancer cells known as disseminated tumor cells or DTCs. But we didn't know the relevance necessarily of those cells that we can detect and study to the ones that arise in your other organs that can lead to death. But eventually we actually had a patient here who was keen on donating her tissue when she died of breast cancer. So we made it happen. Since then we realized, look, you know, this is an important enough issue that we can really do it with cooperation with patients and really, you know, dive into what is their DNA doing. This is where the hibernation data comes in. Given that we had identified parts of the genome that seemed to be in human cells and linked to the evolution of hibernation, can we intersect those data sets with the data sets that we've developed around hibernation to identify what we think are the key genes and switches that are involved in that dormancy state To date 17 patients have shared their cells from both active tumors as well as other distant organs Each sample is a snapshot of living tissue for researchers to study. Some of the first things we've seen is that there's differences in the genes that are turned on when a breast cell is trying to live by itself in the liver versus in the lung. I think that's gonna give us a great handle on what their vulnerabilities are, right? How can we kill them when they're in those vulnerable states by learning how they're surviving now? While the research comparing the data sets is still in its nascent stage, Greg remains determined and hopeful. I can't work on things that will take 20 or 30 years to solve. I fundamentally believe in this idea, and so I think it can be achieved in a reasonable period of time. So what if that same metabolism they're looking to target in cancer cells could also change the game for other health issues, like heart disease? And what if the solution lies in squirrels? Is there a champion hibernator when it comes to animals? Yeah, I mean, 13-line ground squirrels are really good. We call them the Hussein Bolts of hibernators because they're excellent at it. It's a tiny creature that weighs no more than nine ounces at most. Native to central North America, found as far north as Alberta, Canada, and as far south as the Texas coastline, these squirrels undergo remarkable changes during hibernation. They go through what's almost like a mini heart attack or stroke every couple of weeks, so 25 times over hibernation period. That's Ashley Zender, CEO and co-founder of Fauna Bio. The neurons in their brain physically retract during hibernation. So they have a flat EEG. The retinal, the cone photoreceptors in their eye, which see vision, physically melt and reform every couple of weeks. So this is an animal that's evolved over hundreds of millions of years to repair damage that happens during this really dramatic hibernation course using the same genes that you and I have, but in slightly different ways. Today, I'm seeing them up close in Oshkosh, Wisconsin, at the university here. I gotta tell you, I didn't quite know what to expect. I was told I was going to a lab, so I imagined a brightly lit space with lots of test tubes and beakers. But instead, I'm in a dark room known as a hibernaculum. It's lined with shelves of boxes of hibernating animals just stacked one on top of the other. The squirrels here are part of a bred colony being studied by researchers from a biotech company called Fauna Bio. This hibernaculum, as it is called, is set to just 4.5 degrees Celsius, not that far off from the body temperatures of the hibernating squirrels themselves. So they'll spend about one to three weeks in continuous torpor. They'll periodically re-arouse back to normal body temperature. That'll last about 12 hours, and then they'll go back down into torpor, and then this lasts for months. Katie Graybeck is the chief scientific officer and co-founder for Fauna Bio. They lose most of their fat, but they still preserve all of their lean mass, which is quite amazing. They don't lose their muscle. So when they come out, they're ready to run around and mate. This seems like some real lessons in that, in the fact that they maintain that muscle mass, despite the fact they go for months without movement, without eating really anything. Yes, and that's one of the things we're interested in, is how, you know, for us, if we rested in bed just even for a few days, we're going to start losing muscle mass. And then pair that with not eating at all, fasting. You're going to lose a lot of muscle mass. And these animals, not only do they preserve it, it looks like they put on a little bit of muscle before they come out of hibernation. Can we see one of these animals? Can we get a better look? Now, these squirrels are what are called obligate hibernators, which means stimuli like warmth and light will not be enough to keep them from going into torpor. In other words, they are hardwired to hibernate. So here's our hibernating ground squirrel, disease and torpor. Still has reflexes going. So these are just kind of brainstem reflexes? Is that the movement that we're seeing? Let me just take a second to describe what I'm seeing. Katie just took one of the squirrels out of its box, and now it's in a brightly lit lab. It's kind of unfurling and moving its limbs, almost like it's stretching. So most of the brain is shut down right now, and if you did an EEG on brain waves, you wouldn't find much. But two regions of the brain remain active, the hypothalamus and then the brainstem. So that keeps the heart rate going and breathing, everything that's needed for the animal to still be alive and function. And again, all the movement that we're seeing here is just mostly brainstem reflex. Yes. In the hypothalamus, there's certain populations of neurons in the hypothalamus we're finding that are really controlling that suppression of metabolic rate. So the animal goes into torpor. So it's also keeping the animal there in torpor. To go from the deepest state of torpor to fully awake, Graybeck says the squirrel's metabolic activity will spike to around 235 fold from the torpor baseline. That extraordinary jolt is what drives its body temperature from 4 degrees Celsius to 37 degrees Celsius and gets blood flowing again. In all, the process takes just under two hours, and a key part of this transition involves the heart. So we about to see something that very rarely been done Actually I going to do an echocardiogram actually looking at the heart of a squirrel in torpor Hibernating. There's a great short axis view. So did you see the interior of the left ventricle contracting? Oh yeah, I see it. Okay. We're talking about right here. Exactly. Yep. Right there. So that's the interior of the left ventricle. So now he's starting to speed up. So this is a really great example of this animal is still very cold. metabolic rate is still coming up, but his heart is still starting to increase in rates. Within a span of 12 minutes, the squirrel's heart rate went from around 3 beats a minute to more than 107 a minute, eventually reaching the normal range of between 300 to 400 beats per minute. You see the heart rate really rapidly increase, and it's still not getting enough blood flow to the heart itself. Enough oxygen, but it has to work to get the animal to warm up. When the heart is not getting enough blood flow, that's what can cause a heart attack. But that is not happening here. Like, if you measure things, did this squirrel have a heart attack? So when researchers have looked at the histology of the heart, there are markers of damage that look like it had a heart attack. That somehow get repaired for us will lead to long-term heart damage and fibrosis. somehow it can repair it before it goes back down, back into torpor. How? It looks like they're re-expressing the cardiac fetal genes, so involved in stem cell renewal and repair. So we think that some of these squirrels are a little bit more regenerative than what was previously thought. And it kind of makes sense that if they know they're going to damage their heart to get out of torpor, and they have to do this 25 times over the winter, and they have to figure out how to fix it or else they're not going to live very long, right? Whereas for us, that never really happens to us in the course of our lifespans. We're not going to take on damage we know about. So evolutionarily, again, there's pressure to fix things when you damage them. The squirrel's genetic ability to jumpstart its heart so quickly and safely without lasting damage is exactly what Fauna Bio is hoping to mimic. What we're looking at are really two different aspects of cardiac disease. Initially, what we were looking at is really protection from what's called acute myocardial infarctions. Can we protect the heart from damage from that acute injury? But as we started to look particularly at the genomics of our lead program, what we saw is that there were humans with a certain type of heart failure called HEF-PEF. It's a kind of heart failure that affects about half of all heart failure cases around the world. It's really characterized by a stiffness in the heart that doesn't allow blood flow normally. And so how do we have a heart be able to relax and beat better? AI platform to compare data from genetic biobanks of both hibernators and humans around the world. This tech sifts through a combination of compounds and genes looking for one that could turn on the gene to protect human heart cells. They've since entered into preclinical safety trials for a drug that they have identified, developed, and then validated on human cardiac cells in the lab. And so our goal is to really be able to develop new therapeutic approaches for many different diseases and help, at the end of the day, humans live longer and healthier lives, not through hibernation, but through learning insights for how these animals survive this really punishing hibernation cycle. Up next, could these squirrels be the key to getting humans to Mars? This week on The Assignment with me, Adi Cornish. When people ask you on a flight, What do you say you do? My name is Yehuda Duenas. I'm an intimacy coordinator, which means that I help films and productions navigate intimate scenes in film and television. Have you like stopped telling people what you do? Yeah, I've totally stopped telling people what I do. No, no. A Hollywood intimacy coordinator, Yehuda Duenas. We're going to talk about the state of this very new industry and talk about how we tell the story of sex on screen. Listen to The Assignment with me, Audie Cornish, streaming now on your favorite podcast app. The brain. It's the command center for every breath we take, heartbeat, step, and even hibernation. Nature has already shown us what is possible. Now this man, Dr. Jenshiro Tsunagawa, wants to imagine a future where we humans can do it too. Our mission is to make human hibernate. So we are trying to develop a technology which can make human hibernate safely and efficiently. Here at the Rikan Laboratory for Hibernation Research in Kobe, Japan, scientists are studying hibernation using genetically modified mice. In 2020, Dr. Sonagawa was part of a research team that discovered that by triggering specific neurons in the brains of these mice, they could induce torpor. Now, here's the thing. Mice do not naturally hibernate, and neither do humans. And that means this finding could lead us one step closer to a world where scientists can quote, flip the switch on human hibernation. And for us, that could mean a lot. So you can see this guy with the hair is me. You know, Dr. Sonagawa was a pediatrician first, and it was actually his young patients who first inspired his passion in hibernation biology. I was working in an ICU or ER where there are so many severely ill kids But I also learned a lot that even in the current medicine there are so many situations that we cannot even save their lives. And that was kind of striking for me. The more he researched, the more he realized what other benefits inducing hibernation in humans might serve, including saving the lives of critically ill patients being transported to the hospital, during surgery... Just imagine that if you don't need to breathe a lot during hibernation, if the surgery is very small, very short, maybe hibernation will be used instead of general anesthesia. And in organ transplants, where timing is absolutely critical. If we use hibernation at the cellular or tissue level, I think we can use them for preserving organs for the transplants. Beyond emergency medicine, Rican's research here could also make an impact on the way we look at mental health. By studying the responses of stressed mice, Dr. Sonagawa is also in the early stages of research into the link between hibernation and seasonal affective disorder. That's a type of depression linked to the changing of the seasons, especially during winter. He believes the two could share the same origin or core purpose. If this condition share a mechanism, if we go further, if we do enough research about natural hibernation, we might find a new, novel way to deal with this depressive state. I believe that if we discover that this depression system is very similar to hibernation, we can tell those people that depression itself was a kind of function which humans had in the past to survive, for example, the ice age or those periods when we had much more severe winter. and it's not your fault. Hibernation activated. And with the science ever evolving, we come back to the final frontier. The thing that everyone asked me about when I told them I was going to be doing this was space travel. Of course, yeah. Would hibernation be relevant? Yeah, there's been sort of this long intersection of space travel and hibernation. There's this kind of natural linkage between people who are trying to cool humans down to slower their metabolism to enable long-term space travel, whereas these animals reduce their metabolism and thus they get cooler. And so it's kind of this more natural but opposite way to get that metabolic cost savings. In addition to that, we've shown even on Earth that animals, when they're hibernating, are protected, for example, from radiation. That's a big risk for humans as they spend longer time in space. Back in Oshkosh, the race is on to study squirrels in space. Okay, so what are we looking at here? Yeah, so this is what we call the RESPIRES unit. Ryan Sprenger is a senior research physiologist at Fauna Bio. It's a unit that we developed as part of funding that we got from NIAC, NASA Innovative Advanced Concepts. The RESPIRES unit he is showing me is basically a small metal cylinder. And the reason we're developing this unit is because we don't currently have the capability, one, to study hibernation in space, and two, to study physiology in space. So we have designed it to have two synchronously hibernating animals in space transferred to the ISS, and we have it set up so that we can provide air to the animal, we can provide infrared camera viewing. And this is also designed as something called a plethysmograph, which allows us to measure metabolism and ventilation. And we also anticipate telemering the animals. So we can grab as much physiology as we can possibly grab to inform us on what their hibernation phenotype looks like. The thing that you're trying to learn the most here is basically, is hibernation the same in space as it is on Earth? Yeah, I would say that's primary question number one. Does hibernation happen in space and is it the same? Secondary question is, if they do commence hibernation in space, do we see the same protections that we anticipate to see on the ground? Beyond squirrels, researchers at the University of Pittsburgh in Pennsylvania recently concluded studies in conjunction with NASA that put humans in a torpor-like state for up to 20 hours at a time across a five-day period. They did so by using an FDA-approved sedative, dexmedetomidine. In this state, the blood pressure, heart rate, and temperature all dropped among study participants, and their need for food and oxygen also decreased by 20%. And yet they could still wake up quickly and even perform tasks like exercise and operating a computer. Now, they're looking to the next phase of the study to see what impacts these types of torpor-like states could have on the human body. There is so much to learn from these hibernating animals. The things they can teach us, how to prevent heart disease, how to build muscle, treat diabetes, even potentially make it easier for us to go to Mars. So the next time you see an animal burrowing into the ground in the cold winter, recognize there might be some real treatments for all of humanity. Thanks for listening. CNN and next day on the CNN app.
