Hibernation's Genetic Secrets: Unlocking Human 'Superpowers' for Medical Breakthroughs

Researchers trace metabolic superpowers of hibernators to shared DNA

University of Utah HealthAug 1 2025 Animals that hibernate are incredibly resilient. They can spend months without food or water, muscles refusing to atrophy, body temperature dropping to near freezing as their metabolism and brain activity slow to a crawl. When they emerge from hibernation, they recover from dangerous health changes similar to those seen in type 2 diabetes, Alzheimer's disease, and stroke. New genetic research suggests that hibernating animals' superpowers could lie hidden in our own DNA-and provides clues on how to unlock them, opening the door to someday developing treatments that could reverse neurodegeneration and diabetes. Two studies describing the results are published in Science. The genetics of metabolism and obesity A gene cluster called the "fat mass and obesity (FTO) locus" plays an important role in hibernators' abilities, the researchers found. Intriguingly, humans have these genes too. "What's striking about this region is that it is the strongest genetic risk factor for human obesity," says Chris Gregg, PhD, professor in neurobiology, anatomy, and human genetics at University of Utah Health and senior author on the studies. But hibernators seem able to use genes in the FTO locus in new ways to their advantage. The team identified hibernator-specific DNA regions that are near the FTO locus and that regulate the activity of neighboring genes, tuning them up or down. The researchers speculate that adjusting the activity of neighboring genes, including those in or near the FTO locus, allows hibernators to pack on the pounds before settling in for the winter, then slowly use their fat reserves for energy throughout hibernation. Indeed, the hibernator-specific regulatory regions outside of the FTO locus seem crucial for tweaking metabolism. When the researchers mutated those hibernator-specific regions in mice, they saw changes in the mice's weight and metabolism. Some mutations sped up or slowed down weight gain under specific dietary conditions; others affected the ability to recover body temperature after a hibernation-like state or tuned overall metabolic rate up or down. Intriguingly, the hibernator-specific DNA regions the researchers identified weren't genes themselves. Instead, the regions were DNA sequences that contact nearby genes and turn their expression up or down, like an orchestra conductor fine-tuning the volume of many musicians. This means that mutating a single hibernator-specific region has wide-ranging effects extending far beyond the FTO locus, explains Susan Steinwand, research scientist in neurobiology and anatomy at U of U Health and first author on one of the studies. "When you knock out one of these elements-this one tiny, seemingly insignificant DNA region-the activity of hundreds of genes changes," she says. "It's pretty amazing." Understanding hibernators' metabolic flexibility could lead to better treatments for human metabolic disorders like type 2 diabetes, the researchers say. If we could regulate our genes a bit more like hibernators, maybe we could overcome type 2 diabetes the same way that a hibernator returns from hibernation back to a normal metabolic state." Elliott Ferris, MS, bioinformatician at U of U Health and first author on the other study Uncovering the regulation of hibernation Finding the genetic regions that may enable hibernation is a problem akin to excavating needles from a massive DNA haystack. To narrow down the regions involved, the researchers used multiple independent whole-genome technologies to ask which regions might be relevant for hibernation. Then, they started looking for overlap between the results from each technique. First, they looked for sequences of DNA that most mammals share but that had recently changed in hibernators. "If a region doesn't change much from species to species for over 100 million years but then changes rapidly and dramatically in two hibernating mammals, then we think it points us to something that is important for hibernation, specifically," Ferris says. To understand the biological processes that underlie hibernation, the researchers tested for and identified genes that turn up or down during fasting in mice, which triggers metabolic changes similar to hibernation. Next, they found the genes that act as central coordinators, or "hubs," of these fasting-induced changes to gene activity. Many of the DNA regions that had recently changed in hibernators also appeared to interact with these central coordinating hub genes. Because of this, the researchers expect that the evolution of hibernation requires specific changes to the controls of the hub genes. These controls comprise a shortlist of DNA elements that are avenues for future investigation. Awakening human potential Most of the hibernator-associated changes in the genome appeared to "break" the function of specific pieces of DNA, rather than confer a new function. This hints that hibernators may have lost constraints that would otherwise prevent extreme flexibility in the ability to control metabolism. In other words, it's possible that the human "thermostat" is locked to a narrow range of continuous energy consumption. For hibernators, that lock may be gone. Hibernators can reverse neurodegeneration, avoid muscle atrophy, stay healthy despite massive weight fluctuations, and show improved aging and longevity. The researchers think their findings show that humans may already have the needed genetic code to have similar hibernator-like superpowers-if we can bypass some of our metabolic switches. "Humans already have the genetic framework," Steinwand says. "We just need to identify the control switches for these hibernator traits." By learning how, researchers could help confer similar resilience to humans. "There's potentially an opportunity-by understanding these hibernation-linked mechanisms in the genome-to find strategies to intervene and help with age-related diseases," Gregg says. "If that's hidden in the genome that we've already got, we could learn from hibernators to improve our own health." The results are published in Science as "Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice" and "Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus." The research was supported by the National Institutes of Health (grant number T32HG008962), also including the National Institute on Aging (grant numbers R01AG064013 and RF1AG077201), the National Institute of Mental Health (grant number R01MH109577), the National Library of Medicine (grant number T15LM007124). Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of interest statement: Chris Gregg is a co-founder, consultant, and/or has financial interests in Storyline Health Inc., DepoIQ Inc., Primordial AI Inc., and Rubicon AI Inc.; Elliot Ferris is a consultant with financial interests in Primordial AI Inc.; Jared Emery is an employee with financial interests in Storyline Health Inc. University of Utah Health Journal references: Steinwand, S., et al. (2025). Conserved noncoding cis elements associated with hibernation modulate metabolic and behavioral adaptations in mice. Science. doi.org/10.1126/science.adp4701. Ferris, E., et al. (2025). Genomic convergence in hibernating mammals elucidates the genetics of metabolic regulation in the hypothalamus. Science. doi.org/10.1126/science.adp4025.

Hibernation’s Hidden Healing â€~Superpowers’ Could Be Locked in Our DNA

Scientists found genetic elements linked to hibernation in the human genome. Tapping into them could produce a new wave of medical treatments. After spending months without eating, drinking, or moving, hibernating mammals must rebound from extreme physiological changes. Two new studies suggest that the genetic “superpowers†underlying this incredible resilience may also be present in the human genome. For these studies, published Thursday, July 31, in the journal Science, researchers at the University of Utah honed in on the specific DNA regions that help hibernators rapidly recover from muscle atrophy, insulin resistance, and brain damage. They found strong evidence to suggest that the human genome shares these genetic regions, which function as control switches for hibernator adaptations. Finding and harnessing them could lead to new treatments for type 2 diabetes, Alzheimer's disease, and other disorders, the researchers say. “Humans already have the genetic framework,†said Susan Steinwand, a neurobiology and anatomy researcher at U of U Health and first author of one of the studies. “We just need to identify the control switches for these hibernator traits.†During hibernation, mammals enter a state of torpor, or physiological dormancy. This allows them to survive months without food and water, but at great cost to their health. Their muscles deteriorate due to lack of nutrition and movement, Christopher Gregg, a professor of neurobiology at U of U and senior author on both studies, told Gizmodo. Proteins associated with Alzheimer’s disease build up in their brains, and upon awakening, the sudden reperfusion of blood can cause further neurological damage, he explained. What’s more, they become insulin resistant due to the amount of fat they gain to sustain them during months of starvation. Hibernating mammals have evolved remarkable adaptations to reverse this extensive physiological damage. The genes that underlie these adaptations are likely also present in humans and other non-hibernators, Gregg explained. The fact that hibernation has evolved independently in multiple animal species suggests that its basic genetic ingredients are present across the mammalian genome. Therefore, non-hibernators may still carry them. “We mostly all have the same genes across species,†Gregg said. “The big change is in the 98% of the genome that does not encode for genes.†Non-coding DNA is largely responsible for gene regulation. In hibernators, specific regions of non-coding DNA act as “master switches†for controlling functional gene responses to starvation and refeeding, he explained. Finding these master switches in the mammalian genome is like searching for needles in a DNA haystack. To accomplish this, the researchers made whole-genome comparisons across mammals to identify conserved DNA regions that are stable in most species but show accelerated change in hibernators. These hibernator-accelerated regions are regulators that turn genes on in specific cells at specific times, Elliott Ferris, a data analyst in Gregg’s lab at U of U and first author of one of the studies, told Gizmodo. To understand the biological processes that may be linked to these hibernator-accelerated regions, the researchers identified genes that get turned up or turned down during fasting in mice. Hibernation is an adaptation to survive food scarcity, so fasting triggers similar metabolic changes. This led them to “hub genes†that act as master regulators for fasting-induced changes to gene activity. “The really surprising discovery that was very exciting was that the hibernation-linked elements are disproportionately affecting those key hub genes,†Gregg explained. “The implication is that hibernators changed the regulation and activity of these core hub genes to have big downstream effects on the whole program for responding to food scarcity and food deprivation. That’s important as we think about translating this knowledge into the real world.†Gregg is co-founder of Primordial AI, a Utah-based biotech startup that leverages AI to uncover master regulator gene drug targets. Through this company, he aims to develop drugs that mimic the genetic advantages hibernators have, such as boosting neuroprotection in Alzheimer’s patients or reversing insulin resistance in type 2 diabetics. “Those hub genes are the ones that we think are a really good starting point to design medicines to affect those genes,†Gregg said.

Hibernator "Superpowers" May Lie Hidden in Human DNA | Newswise

Newswise -- Animals that hibernate are incredibly resilient. They can spend months without food or water, muscles refusing to atrophy, body temperature dropping to near freezing as their metabolism and brain activity slow to a crawl. When they emerge from hibernation, they recover from dangerous health changes similar to those seen in type 2 diabetes, Alzheimer's disease, and stroke. New genetic research suggests that hibernating animals' superpowers could lie hidden in our own DNA -- and provides clues on how to unlock them, opening the door to someday developing treatments that could reverse neurodegeneration and diabetes. Two studies describing the results are published in Science. A gene cluster called the "fat mass and obesity (FTO) locus" plays an important role in hibernators' abilities, the researchers found. Intriguingly, humans have these genes too. "What's striking about this region is that it is the strongest genetic risk factor for human obesity," says Chris Gregg, PhD, professor in neurobiology, anatomy, and human genetics at University of Utah Health and senior author on the studies. But hibernators seem able to use genes in the FTO locus in new ways to their advantage. The team identified hibernator-specific DNA regions that are near the FTO locus and that regulate the activity of neighboring genes, tuning them up or down. The researchers speculate that adjusting the activity of neighboring genes, including those in or near the FTO locus, allows hibernators to pack on the pounds before settling in for the winter, then slowly use their fat reserves for energy throughout hibernation. Indeed, the hibernator-specific regulatory regions outside of the FTO locus seem crucial for tweaking metabolism. When the researchers mutated those hibernator-specific regions in mice, they saw changes in the mice's weight and metabolism. Some mutations sped up or slowed down weight gain under specific dietary conditions; others affected the ability to recover body temperature after a hibernation-like state or tuned overall metabolic rate up or down. Intriguingly, the hibernator-specific DNA regions the researchers identified weren't genes themselves. Instead, the regions were DNA sequences that contact nearby genes and turn their expression up or down, like an orchestra conductor fine-tuning the volume of many musicians. This means that mutating a single hibernator-specific region has wide-ranging effects extending far beyond the FTO locus, explains Susan Steinwand, research scientist in neurobiology and anatomy at U of U Health and first author on one of the studies. "When you knock out one of these elements -- this one tiny, seemingly insignificant DNA region -- the activity of hundreds of genes changes," she says. "It's pretty amazing." Understanding hibernators' metabolic flexibility could lead to better treatments for human metabolic disorders like type 2 diabetes, the researchers say. "If we could regulate our genes a bit more like hibernators, maybe we could overcome type 2 diabetes the same way that a hibernator returns from hibernation back to a normal metabolic state," says Elliott Ferris, MS, bioinformatician at U of U Health and first author on the other study. Finding the genetic regions that may enable hibernation is a problem akin to excavating needles from a massive DNA haystack. To narrow down the regions involved, the researchers used multiple independent whole-genome technologies to ask which regions might be relevant for hibernation. Then, they started looking for overlap between the results from each technique. First, they looked for sequences of DNA that most mammals share but that had recently changed in hibernators. "If a region doesn't change much from species to species for over 100 million years but then changes rapidly and dramatically in two hibernating mammals, then we think it points us to something that is important for hibernation, specifically," Ferris says. To understand the biological processes that underlie hibernation, the researchers tested for and identified genes that turn up or down during fasting in mice, which triggers metabolic changes similar to hibernation. Next, they found the genes that act as central coordinators, or "hubs," of these fasting-induced changes to gene activity. Many of the DNA regions that had recently changed in hibernators also appeared to interact with these central coordinating hub genes. Because of this, the researchers expect that the evolution of hibernation requires specific changes to the controls of the hub genes. These controls comprise a shortlist of DNA elements that are avenues for future investigation. Most of the hibernator-associated changes in the genome appeared to "break" the function of specific pieces of DNA, rather than confer a new function. This hints that hibernators may have lost constraints that would otherwise prevent extreme flexibility in the ability to control metabolism. In other words, it's possible that the human "thermostat" is locked to a narrow range of continuous energy consumption. For hibernators, that lock may be gone. Hibernators can reverse neurodegeneration, avoid muscle atrophy, stay healthy despite massive weight fluctuations, and show improved aging and longevity. The researchers think their findings show that humans may already have the needed genetic code to have similar hibernator-like superpowers -- if we can bypass some of our metabolic switches. "Humans already have the genetic framework," Steinwand says. "We just need to identify the control switches for these hibernator traits." By learning how, researchers could help confer similar resilience to humans. "There's potentially an opportunity -- by understanding these hibernation-linked mechanisms in the genome -- to find strategies to intervene and help with age-related diseases," Gregg says. "If that's hidden in the genome that we've already got, we could learn from hibernators to improve our own health." ### The results are published in Science as "Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice" and "Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus." The research was supported by the National Institutes of Health (grant number T32HG008962), also including the National Institute on Aging (grant numbers R01AG064013 and RF1AG077201), the National Institute of Mental Health (grant number R01MH109577), the National Library of Medicine (grant number T15LM007124). Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of interest statement: Chris Gregg is a co-founder, consultant, and/or has financial interests in Storyline Health Inc., DepoIQ Inc., Primordial AI Inc., and Rubicon AI Inc.; Elliot Ferris is a consultant with financial interests in Primordial AI Inc.; Jared Emery is an employee with financial interests in Storyline Health Inc.