When ground squirrels hibernate in the winter, they stop eating and survive solely on the fat reserves they have stored in their bodies. Such a prolonged period of fasting and inactivity should significantly reduce muscle mass and function. However, this is surprisingly not happening: the animals usually emerge from hibernation in the spring in a very good shape, ready for the intense physical activity associated with their mating season. Until recently, this phenomenon has been a mystery for scientists.
According to a new study led by the University of Montreal, hibernators harness a metabolic trick of their gut microbiome to recycle the nitrogen from urea (a waste compound eliminated as urine during periods of non-hibernation) and use it to build new tissue proteins.
By studying the urea salvage process in 13-lined ground squirrels, the scientists found that the incorporation of urea nitrogen into their tissue protein was highest during late winter – unlike most physiological processes during hibernation, which tend to be significantly reduced. Moreover, the gut microbes themselves seemed to be using the urea nitrogen to build their own proteins, thus making the relationship between squirrels and their microbiome a truly symbiotic one.
These findings have important potential implications for space travel. Since astronauts currently face muscle-loss problems caused by microgravity-induced suppression of protein synthesis, this discovery could open ways of augmenting their muscle protein synthesis processes using urea nitrogen salvage.
“Because we know which muscle proteins are suppressed during spaceflight, we can compare these proteins with those that are enhanced by urea nitrogen salvage during hibernation,” said study lead author Matthew Regan, an assistant professor of Animal Physiology at the University of Montreal. “If there is an overlap between the proteins in spaceflight and the ones from hibernation, then it suggests this process may have benefits to muscle health during spaceflight.”
Moreover, these discoveries could also help solve more pressing Earth-bound problems, such as muscle mass decline caused by starvation in underdeveloped countries or old age. “The mechanisms that mammals like the 13-lined ground squirrel have naturally evolved to maintain protein balance in their own nitrogen-limited situations may inform strategies for maximizing the health of other nitrogen-limited animals, including humans,” said Regan.
A possible solution would be the development of pre- or probiotic pills to promote a gut microbiome such as that of hibernating animals.
“To be clear, these applications, though theoretically possible, are a long way from delivery, and a lot of additional work is needed to translate this naturally evolved mechanism safely and effectively to humans. But one thing I find encouraging is that a study from the early 1990s provided some evidence that humans are capable of recycling small amounts of urea nitrogen via this same process. This suggests that the necessary machinery is in place. It just needs to be optimized,” Regan concluded.
The study is published in the journal Science.