Recent research conducted by scientists at the University of Utah sheds light on unlocking hibernation abilities, potentially paving the way for treatments that could reverse neurodegeneration and diabetes.
Investigating the evolution of hibernation in certain species like helinates, bats, ground squirrels, and lemurs can unveil the mysteries of their extraordinary resilience. Image credit: Chrissy Richards.
Gene clusters known as fat mass and obesity (FTO) loci are crucial to understanding hibernation capabilities. Interestingly, these genes are also present in humans.
“What stands out in this region is that it represents the most significant genetic risk factor for obesity in humans,” states Professor Chris Greg, the lead author of both studies from the University of Utah.
“Hibernators seem to leverage genes in the FTO locus uniquely.”
Professor Greg and his team discovered DNA regions specific to hibernation factors near the FTO locus that regulate the expression of nearby genes, modulating their activity.
They hypothesize that hibernators can accumulate weight prior to entering winter by adjusting the expression of adjacent genes, particularly those at or near the FTO locus, utilizing fat reserves gradually for winter energy needs.
Moreover, regulatory regions linked to hibernation outside the FTO locus appear to play a significant role in fine-tuning metabolism.
When the research team mutated these hibernation factor-specific regions in mice, they observed variations in body weight and metabolism.
Some mutations accelerated or inhibited weight gain under specific dietary conditions, while others affected the mice’s ability to restore body temperature post-hibernation or regulate their overall metabolic rate.
Interestingly, the hibernator-specific DNA regions identified by researchers are not genes themselves.
Instead, this region comprises a DNA sequence that interacts with nearby genes, modulating their expression like conductors guiding an orchestra to adjust volume levels.
“This indicates that mutating a single hibernator-specific region can influence a broad array of effects well beyond the FTO locus,” notes Dr. Susan Steinwand from the University of Utah. First study.
“Targeting a small, inconspicuous DNA region can alter the activity of hundreds of genes, which is quite unexpected.”
Gaining insight into the metabolic flexibility of hibernators may enhance the treatment of human metabolic disorders like type 2 diabetes.
“If we can manipulate more genes related to hibernation, we may find a way to overcome type 2 diabetes similar to how hibernators transition back to normal metabolic states,” says Dr. Elliot Ferris, Ph.D., of the University of Utah. Second survey.
Locating genetic regions associated with hibernation poses a challenge akin to extracting needles from a vast haystack of DNA.
To pinpoint relevant areas, scientists employed various whole-genome technologies to investigate which regions correlate with hibernation.
They then sought overlaps among the outcomes of each method.
Firstly, they searched for DNA sequences common to most mammals that have recently evolved in hibernators.
“This region has remained relatively unchanged among species for over 100 million years; however, if significant alterations occur in two hibernating mammals, it signals critical features for hibernation,” remarked Dr. Ferris.
To comprehend the biological mechanisms of hibernation, researchers tested and identified genes that exhibited fluctuations during fasting in mice, producing metabolic alterations similar to those seen in hibernation.
Subsequently, they identified genes that serve as central regulators or hubs for these fasting-induced gene expressions.
Numerous recently altered DNA regions in hibernators appear to interact with these central hub genes.
Consequently, the researchers predict that the evolution of hibernation necessitates specific modulations in hub gene regulation.
These regulatory mechanisms constitute a potential candidate list of DNA elements for future investigation.
Most alterations related to hibernation factors in the genome seem to disrupt the function of specific DNA rather than impart new capabilities.
This implies that hibernation may have shed constraints, allowing for great flexibility in metabolic control.
In essence, the human metabolic regulator is constrained to a narrow energy expenditure range, whereas, for hibernators, this restriction may not exist.
Hibernation not only reverses neurodegeneration but also prevents muscle atrophy, maintains health amidst significant weight fluctuations, and suggests enhanced aging and longevity.
Researchers surmise that their findings imply if humans can bypass certain metabolic switches, they may already possess a genetic blueprint akin to a hibernation factor superpower.
“Many individuals may already have the genetic structure in place,” stated Dr. Steinwand.
“We must identify the control switches for these hibernation traits.”
“Mastering this process could enable researchers to bestow similar resilience upon humans.”
“Understanding these hibernation-associated genomic mechanisms provides an opportunity to potentially intervene and devise strategies for tackling age-related diseases,” remarks Professor Greg.
“If such mechanisms are embedded within our existing genome, we could learn from hibernation to enhance our health.”
The findings are published in two papers in the journal Science.
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Susan Steinwand et al. 2025. Conserved non-coding CIS elements associated with hibernation regulate metabolism and behavioral adaptation in mice. Science 389 (6759): 501-507; doi: 10.1126/science.adp4701
Elliot Ferris et al. 2025. Genome convergence in hibernating mammals reveals the genetics of metabolic regulation of the hypothalamus. Science 389 (6759): 494-500; doi: 10.1126/science.adp4025
Source: www.sci.news
