Hibernating mammals rely on specific genes to regulate metabolism, entering their unique, low-energy state, where humans actually carry the same hibernation-related DNA.
Now, early research suggests that leveraging this particular DNA could help people treat their medical conditions, scientists say.
Hibernation offers “a bunch of different biometrically important superpowers” to senior research author Christopher Gregg, professor of human genetics at the University of Utah.
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For example, ground squirrels can develop reversible insulin resistance, which can help you gain weight quickly before hibernation, but they begin to fade when hibernation begins. A better understanding of how Hibernators can turn this switch over could help address the insulin resistance that characterizes type 2 diabetes, Greg suggested.
Hibernating animals also protect the nervous system from damage that can be caused by sudden changes in blood flow. “When they get out of hibernation, their brains are being reperfused with blood,” Greg said. “In many cases, it would cause a lot of damage, like a stroke, but they have developed ways to prevent that damage from occurring.”
Greg and his colleagues believe that tapping people’s hibernation-related genes can unlock similar benefits.
Related: Best Maps of the Human Genome Shedding Light on “Jump Genes”, Junk DNA, etc.
The “hub” of hibernation genes
In a pair of studies published Thursday (July 31) in Journal Science, Greg and his team identified key levers that regulate hibernation-related genes, showing how they differ between hibernating and non-hibernating animals. Next, lab experiments delved into the effect of removing these levers in lab mice.
Mice do not hibernate, but after fasting for at least 6 hours, they are in a lethargic state of metabolism, movement and temperature drops that usually lasts less than one day. This has made mice an appropriate genetic model to study these effects.
Scientists have designed five unconserved mice using the gene editing technology CRISPR to design five unconserved mice where five conserved non-coding CIS elements (CRES) have been deactivated or “knocked out.” These CREs act as levers to control genes encoding proteins that perform biological functions.
The CRES targeted in this study are located near a gene cluster or FTO locus known as the “fat mass and obesity-related locus.” This can also be seen in humans. Genetic mutants found within the cluster are associated with an increased risk of obesity and related conditions. Broadly speaking, FTO trajectories are known to be important for controlling metabolism, energy expenditure, and weight.
Knocking out CRES allowed researchers to change the weight, metabolic rate, and foraging behavior of mice. Some deletions increased or slowed weight gain, increased or decreased metabolic rates, while some deletions affected how quickly the temperature of mice recovered after Tolpopo, the researchers said in a statement.
The finding is “very promising,” and especially given the FTO locus plays a well-known role in human obesity, Kelly Drew, hibernation biology expert at the University of Alaska Fairbanks University, told Live Science in an email.
One CRE (called E1) was knocked out in female mice. Removing another CRE called E3 changed the foraging behavior of both male and female mice, particularly the way they search for food hidden in the arena.
“This suggests that important differences between foraging and decision-making processes may exist between hibernation and non-craftsmen, and that the elements we find may be involved,” Greg said.
Unknown to deal with
The study authors stated that the results could be human-related because the underlying genes do not differ significantly between mammals. “That’s the way [the mammals] In various combinations that turn these genes on and off at different times and form different species,” Greg said.
But “it’s not as simple as introducing the same changes into human DNA,” Joanna Kelly, a professor specializing in functional genomics at the University of California, Santa Cruz, told Live Science in an email. “Humans cannot provide fast-induced nutrition, which is why mice are used in these studies,” said Kelly, who was not involved in the job.
She suggested that future work includes animals that cannot be sclerosed and focus on unpacking all downstream effects of deleted CRE. As it stands, she added, current research “definitely points to the field in a new direction” in terms of how scientists understand genetic controls that drive hibernator changes throughout the year.
Drew also emphasized that while resistance in mice is caused by fasting, true hibernation is caused by hormones and seasonal changes and internal clocks. Therefore, CRES and genes are likely an important part of the metabolic “tool kit” that responds to fasting, but may not be “master switches” that turn hibernation on or off.
“Nevertheless, discovering these basic mechanisms in easy-to-use models like mice is an invaluable stepping stone for future research,” Drew said.
Greg highlighted that many remain unknown, including why some deletion effects differ between male and male mice and how changes in foraging behavior seen in mice appear in humans. The team will also investigate what happens when multiple hibernation link CREs are removed at once with the mouse.
In Line, Greg believes it is possible to use drugs to fine-tune the activity of human “hibernation hub genes.” This approach means that patients may provide benefits for their gene activity, like neurodepressants, without actually hibernating.
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