Discovering Hibernation’s Genetic Secrets
After enduring months of inactivity, without food or water, hibernating animals undergo significant physiological changes before they can fully recover. Two recent studies indicate that the remarkable genetic capabilities that enable this resilience may also exist within the human genome.
Published on Thursday, July 31, researchers from the University of Utah focused on specific DNA regions that facilitate rapid recovery from muscle wasting, insulin resistance, and brain injury in hibernators. They found compelling evidence suggesting that these genetic areas are present in humans as well. These regions serve as control switches for adaptations seen in hibernating species. The researchers propose that discovering and utilizing these genes could lead to innovative treatments for conditions like type 2 diabetes and Alzheimer’s disease.
“Humans already possess the genetic foundation,” noted Susan Steinwand, a researcher in neurobiology and anatomy and the lead author of one of the studies. “We simply need to pinpoint the control switches that govern these hibernator traits.”
During hibernation, mammals enter a state of torpor—a type of physiological dormancy that allows them to survive extended periods without sustenance; however, it’s not without significant health repercussions. Muscle degradation occurs from lack of activity and nutrition, while proteins linked to Alzheimer’s accumulate in the brain. Upon waking, a rush of blood can lead to additional neurological harm. Moreover, the fat accumulation during this period causes insulin resistance.
Amazing adaptations allow hibernating mammals to counteract such extensive physiological damage. The genes behind these adaptations likely also exist in humans and other non-hibernating species. Christopher Gregg, a neurobiology professor and senior author on both studies, explained that the independent evolution of hibernation among various species suggests that the fundamental genetic components are shared across mammals. As such, even non-hibernators may harbor these genes.
“Most species share similar genes,” Gregg explained. “The real difference lies within the 98% of the genome that doesn’t code for actual genes.” This non-coding DNA plays a crucial role in gene regulation. In hibernators, certain areas of non-coding DNA function as “master switches” regulating gene responses to both starvation and subsequent refeeding.
Identifying these master switches in the mammalian genome can be quite a challenge, akin to finding needles in a haystack of DNA. To tackle this, the researchers conducted whole-genome comparisons across different mammals to locate conserved DNA regions that remain stable in most species but exhibit accelerated variation in hibernators. These accelerated regions regulate gene activation in specific cells at the right moments, according to Elliott Ferris, a data analyst in Gregg’s lab and the lead author of another study.
To delve into the biological processes associated with these hibernator-accelerated regions, the team examined genes that are upregulated or downregulated during fasting in mice. Given that hibernation serves as an adaptation to food scarcity, the metabolic changes triggered by fasting are somewhat similar. This investigation led to the discovery of “hub genes,” which function as master regulators of gene activity alterations catalyzed by fasting.
“We found it quite striking that hibernation-related elements appear to have a disproportionate impact on these significant hub genes,” Gregg remarked. “This suggests that hibernators have adapted the regulation and function of these core genes to promote extensive effects on the entire biological response to food scarcity. This insight is crucial as we ponder how to apply this knowledge practically.”
Gregg is also a co-founder of Primordial AI, a biotech startup based in Utah that utilizes AI to identify potential gene drug targets. Through this venture, he hopes to create drugs that replicate the genetic advantages seen in hibernators—such as enhancing neuroprotection in Alzheimer’s patients or reversing insulin resistance in type 2 diabetes. “We believe those hub genes are a promising starting point for designing medications to influence those genetic pathways,” Gregg stated.
