Hibernator “Superpowers” Could Help Humans Treat Diabetes and Alzheimer’s

Genetic switches near the FTO locus may enable hibernators’ extreme metabolic resilience and could inspire future treatments for human metabolic and age-related diseases.

Animals that hibernate display remarkable biological resilience. They can remain inactive for months without eating or drinking. During this time, their muscles avoid wasting away, their body temperature drops close to freezing, and both metabolism and brain activity slow dramatically. Yet when these animals wake from hibernation, they recover from conditions that resemble serious human illnesses such as type 2 diabetes, Alzheimer’s disease, and stroke.

Recent genetic studies suggest that the abilities that allow hibernators to survive such extreme conditions may be linked to DNA sequences that humans also possess. These findings provide clues about how similar biological mechanisms might be activated in people, potentially leading to new approaches for treating neurodegeneration and diabetes.

The research findings are described in two studies published in Science.

The FTO Gene Cluster and Obesity Link

Scientists found that a group of genes known as the “fat mass and obesity (FTO) locus” plays an important role in the biology of hibernating animals. Humans also carry this same gene cluster. “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. However, hibernating species appear able to use these genes in ways that benefit their survival.

The researchers discovered specialized DNA regions in hibernators located near the FTO locus. These regions regulate nearby genes by increasing or decreasing their activity. The team believes this genetic regulation may help animals build up large fat reserves before winter begins and then gradually burn that stored energy throughout the hibernation period.

Experiments also revealed that these regulatory DNA regions play a key role in controlling metabolism. When scientists altered these hibernator-specific DNA segments in mice, they observed changes in body weight and metabolic activity. Certain mutations affected how quickly the mice gained weight depending on their diet. Others influenced how well the animals recovered body temperature after entering a hibernation-like state or altered their overall metabolic rate.

Regulatory DNA Controls Metabolism

Interestingly, the DNA segments identified by the researchers are not genes themselves. Instead, they function as regulatory elements that interact with nearby genes and adjust their activity levels, similar to how a conductor directs the volume and timing of musicians in an orchestra.

Because these elements influence many genes at once, altering a single regulatory region can have far-reaching effects. Susan Steinwand, research scientist in neurobiology and anatomy at U of U Health and first author on one of the studies, explains that the impact can be surprisingly large. “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.”

The ability of hibernating animals to shift their metabolism so dramatically may provide insights for treating metabolic diseases in humans. “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.

Searching the Genome for Hibernation Clues

Identifying genetic regions involved in hibernation is a complex challenge, comparable to locating a few needles in an enormous DNA haystack. To narrow their search, the researchers used several independent whole genome analysis methods to determine which parts of the genome might be involved. They then compared the results from these approaches to find areas of overlap.

One strategy focused on DNA sequences that remain largely unchanged across most mammals but show recent alterations in hibernating species. “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.

The scientists also investigated the biological processes that occur during hibernation by examining mice that were fasting, which triggers metabolic changes similar to those seen during hibernation. From these experiments, they identified genes that increase or decrease their activity during fasting. They then determined which genes act as central coordinators, or “hubs,” that control these widespread changes.

Hub Genes and Evolutionary Changes

Many of the DNA regions that had recently evolved in hibernating species appeared to interact with these hub genes. This suggests that the evolution of hibernation may depend on changes in the regulatory controls that manage these central genes. These regulatory sequences now represent promising targets for further research.

The researchers also noticed that many genetic changes in hibernators appear to disrupt or weaken the original function of certain DNA elements rather than create entirely new functions. This observation suggests that hibernating species may have lost genetic constraints that normally limit how flexible metabolism can be. In comparison, human metabolism may operate within a narrower range of energy use. In hibernating animals, those limitations may no longer exist.

Hibernating species can recover from neurodegeneration, prevent muscle loss, remain healthy despite dramatic changes in body weight, and often show signs of improved longevity. The researchers believe their findings indicate that humans may already carry the genetic foundation needed for similar protective abilities if scientists can learn how to adjust the relevant metabolic controls.

Unlocking Hibernation Traits in Humans

“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.”

References:

“Conserved noncoding cis elements associated with hibernation modulate metabolic and behavioral adaptations in mice” by Susan Steinwand, Cornelia Stacher Hörndli, Elliott Ferris, Jared Emery, Josue D. Gonzalez Murcia, Adriana Cristina Rodriguez, Riley J. Spotswood, Amandine Chaix, Alun Thomas, Crystal Davey and Christopher Gregg, 31 July 2025, Science.
DOI: 10.1126/science.adp4701

“Genomic convergence in hibernating mammals elucidates the genetics of metabolic regulation in the hypothalamus” by Elliott Ferris, Josue D. Gonzalez Murcia, Adriana Cristina Rodriguez, Susan Steinwand, Cornelia Stacher Hörndli, Dimitri Traenkner, Pablo J. Maldonado-Catala and Christopher Gregg, 31 July 2025, Science.
DOI: 10.1126/science.adp4025

This study was funded by NIH/National Institutes of Health, NIH/National Institute on Aging, NIH/National Institute on Aging, NIH/National Institute of Mental Health, and NIH/National Library of Medicine.

Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.