Humans have unused sequences in their DNA similar to those that allow hibernating animals to modify their metabolism. Activated appropriately, these sequences could help fight many metabolic or neurodegenerative diseases such as obesity or Alzheimer's, and even aging, suggests a new study published in the journal Science.
Hibernation involves being able to modify one's metabolism
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“ We identified 10,251 short sequences in the human genome that may regulate processes associated with mammalian hibernation", comments to Science and Future Elliott Ferris, a bioinformatician at the University of Utah Hospital (USA) and first author of this work. If we don't hibernate, it would not be because our DNA no longer contains the necessary genes, but because the sequences that regulate their activity like switches keep them dormant.
“ If we could regulate our genes a little more like hibernating animals, we might be able to beat type 2 diabetes in the same way that a hibernating animal returns from hibernation to a normal metabolic state.", comments Elliott Ferris. Hibernating animals have the ability to profoundly alter their metabolism and physiology by gaining up to 50% of body mass before winter, then slowly consuming these reserves, notably thanks to a mechanism of insulin resistance.
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To learn more, the team is observing the activation of mice's genes when they enter a state of torpor induced by fasting, and then when they are fed again. Torpor is related to hibernation in that body temperature decreases and metabolism slows down – it is likely an intermediate trait between hibernation and homeothermy (as in humans, editor’s note),” explains the bioinformatician.
The scientists then compare the areas affected by these genetic modulations to the regions that they identified as not only conserved in most mammals, but whose evolution had been accelerated in those that hibernate. If a region doesn't change much across species for over 100 million years, but then changes rapidly and dramatically in two hibernating mammals, then we think that tells us something important about hibernation in particular.", reasons Elliott Ferris.
Hibernation regulatory genes potentially actionable in humans
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Impressed, the researchers observed in mice in a state of torpor that these modulations of genetic activity allowed the stopping of neurodegeneration processes in the hypothalamus – an area of the brain regulating metabolism, feeding, thermogenesis and torpor. We observed changes in hypothalamic gene expression. These changes were particularly pronounced during refeeding.", reveals Elliott Ferris. The more than 10,000 matching sequences identified in the human genome regulate genes that impact insulin resistance, adiposity, and neurodegenerative diseases," adds the researcher. These switches capable of activating these hidden capacities in our DNA could therefore be targets for future treatments specific to these sequences.
These could be valuable targets for altering human gene expression to treat diseases ranging from type 2 diabetes and obesity to muscle atrophy and neurodegeneration.
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