Animals that hibernate are hardy and resilient; they can hunker down and go months without eating or drinking, yet their muscles don't atrophy without use, and their metabolic and brain functions slow down significantly. After coming out of hibernation, these creatures can recover from health problems that mimic some serious diseases. Two new studies aimed to reveal more about the genetic basis of hibernation, and find similar abilities that might be hidden in human DNA. This work, which was reported in two new studies in Science, could help researchers develop treatments or preventive approaches for some human diseases.
In this effort, the investigators searched for genes and gene regions that were important to hibernators' abilities. They looked for sequences that had not changed much from one hibernator to another during evolution; these conserved regions were likely to be important.
The investigators also used a mouse model that was subjected to periods of fasting, then the researchers looked for genes, or gene regulators that became more or less active during these periods. These regulators were not genes that express protein, but they could modulate the expression of other genes.
One cluster of genes known as the fat mass and obesity (FTO) locus was found to be critical to hibernation. Although the scientists noted that this cluster is strongly linked to human obesity, hibernators seem to use genes in the FTO region to their benefit.
The investigators found sequences of DNA near the FTO locus in hibernators, which appear to help control the expression of neighboring genes. This could be a way for hibernators to add pounds before they settle into hibernation, so they can use these reserves as they rest.
When the researchers modified these regulatory regions in mice, the metabolism and weight of the mice changed. Some modifications caused the mice to gain more (or less) weight when they were given certain diets (compared to unmodified mice). Other genetic changes altered the metabolic rates of the mice, or affected body temperature.
Since regulatory sequences in this region can impact many genes, mutations in those regions can also have major impacts, the investigators noted.
"When you knock out one of these elements—this one tiny, seemingly insignificant DNA region—the activity of hundreds of genes changes. It's pretty amazing," said a first study author, Susan Steinwand, a research scientist at the University of Utah Health Sciences (U of U health).
These genetic features could provide new insights into how to prevent or treat some human disorders.
"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," said a first study author Elliott Ferris, MS, a bioinformatician at U of U Health.
Since hibernators are able to reverse neurodegeneration, prevent muscle atrophy, live longer, and remain healthy during huge changes in weight fluctuations, the researchers are interested in finding ways to unlock these abilities in humans. It may be possible to do so by altering some regulatory sequences.
"Humans already have the genetic framework," Steinwand said. "We just need to identify the control switches for these hibernator traits."
Sources: University of Utah Health Sciences, Ferrius et al Science 2025, Steinwand et al Science 2025