What wintering squirrels can teach astronauts
The unique way that ground squirrels burn almost no energy when they
hibernate - with no loss of muscle mass - has implications for space travel


Date:
January 27, 2022
Source:
University of Montreal
Summary:
The unique way that ground squirrels burn almost no energy when
they hibernate -- with no loss of muscle mass -- has implications
for space travel, biologists find.



FULL STORY ==========================================================================
When bears and ground squirrels hibernate in winter, they stop eating,
lasting until spring simply on the fat reserves they've stored up in
their bodies.

Usually, this sort of prolonged fasting and inactivity would significantly reduce the mass and function of muscle, but hibernators don't suffer
this fate.

How they avoid it, however, has been a mystery.


==========================================================================
Now, in research published in Science, an Universite' de Montre'al
biologist has figured out why, and his findings could have implications
for, of all things, the future of space travel . By studying a variety
called the 13-lined ground squirrel that is common in North America,
Matthew Regan has confirmed a theory known as "urea nitrogen salvage"
dating back to the 1980s.

The theory posits that hibernators harness a metabolic trick of their gut microbes to recycle the nitrogen present in urea, a waste compound that
is usually excreted as urine, and use it to build new tissue proteins.

How could this discovery be of use in space? Theoretically, Regan posits,
by helping astronauts minimize their own muscle-loss problems caused
by microgravity-induced suppression of protein synthesis and which they
now try to reduce by intensively exercising.

If a way could be found to augment the astronauts' muscle protein
synthesis processes using urea nitrogen salvage, they could be able
to achieve better muscle health during long voyages into deep space in spacecraft too small for the usual exercise equipment, the argument goes.

"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 Regan, who carried out this
research while a postdoc at the University of Wisconsin-Madison.



==========================================================================
He is now continuing his work through a Canadian Space Agency research
grant at UdeM, where he last year took up a position as assistant
professor of animal physiology in the Department of Biological Sciences.

"If," Regan continued, "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."
A model hibernator In his study, Regandesigned a series of techniques and experiments to investigate the major steps in the urea salvage process
and provide evidence for whether or not they occur in the 13-lined ground squirrel when it hibernates.

To do that, in their lab they injected their test squirrels' blood with "double-labeled" urea, meaning the urea's carbon atom was 13C instead
of the usual 12C, and its nitrogen atoms were 15N instead of the usual
14N. These labels allowed them to track the urea-sourced carbon and
nitrogen through the different steps of the urea nitrogen salvage process.



==========================================================================
That process, they found, led from the initial transport of urea from
the blood into the gut, to the breakdown of urea into its component
parts by gut microbes, to the flow of substances -- called metabolites
-- containing urea nitrogen back into the animal, and finally to the
eventual appearance of this urea nitrogen in tissue protein.

"Essentially, seeing 13C and/or 15N in metabolites at these various steps indicated that they originated from urea, and thus, that the hibernator
was using urea nitrogen salvage," said Regan.

He did his experiments on squirrels with and without gut microbiomes
at three times of the year: summer, when they were active and not
hibernating; early winter, when they were one month into fasting and hibernation; and late winter, when they were four months into fasting
and hibernation.

'Clear evidence of nitrogen salvage' What they found was definitive:
at each step of the process, there was clear evidence of urea nitrogen
salvage by the squirrels with intact gut microbiomes.

Importantly, the squirrels with depleted gut microbiomes displayed no
evidence of urea nitrogen salvage at any step, confirming this process
was wholly dependent on the gut microbes' ability to degrade urea,
something the squirrels themselves cannot do.

Regan and his team also made two other important findings:
* First, the incorporation of urea nitrogen into the tissue protein
of the
squirrels was highest during late winter, suggesting that urea
nitrogen salvage becomes more active as the hibernation season
proceeds. This is unlike most physiological processes during
hibernation, when tend to be significantly reduced.

* Second, there was evidence the microbes themselves were using
the urea
nitrogen to build their own new proteins, which is useful for them
because they, like the squirrel, are under conditions of fasting
hibernation. Thus, both the squirrel and its microbes benefit from
urea nitrogen salvage, which makes this process a true symbiosis.

What this means, Regan said, is that the squirrels emerge from hibernation
in the spring in good shape. This is important because the year's only
mating season, which is a time of intense physical activity for both males
and females, occurs directly after they emerge from hibernation. Tissue function - - particularly muscle tissue function -- is therefore highly important for a successful mating season.

"By facilitating muscle protein synthesis late in the hibernation season,
urea nitrogen salvage may help optimize the emerging squirrels' muscle
function and contribute to their reproductive success during the mating season," said Regan.

"Urea nitrogen salvage may therefore enhance the animals' overall
biological fitness." Starving masses and the elderly Beyond the
implications for space travel and the health of astronauts, Regan's
discovery could have more immediate impacts now right here on Earth --
in the starving masses of the underdeveloped world, and in the elderly.

Hundreds of millions of people globally experience muscle wasting as
a consequence of various conditions -- undernourishment, for instance,
affects over 805 million people globally. More prevalent in Canada is sarcopenia, an age-related decline in muscle mass stemming from anabolic insensitivity that affects all humans, leading to a 30- to 50-per-cent
decline in skeletal muscle mass between the ages 40 and 80.

"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. One solution might be to develop a pre- or probiotic pill that
people could take to promote a gut microbiome of the kind that hibernators
like squirrels have.

"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," Regan said.

"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." ========================================================================== Story Source: Materials provided by University_of_Montreal. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Matthew D. Regan, Edna Chiang, Yunxi Liu, Marco Tonelli, Kristen M.

Verdoorn, Sadie R. Gugel, Garret Suen, Hannah V. Carey, Fariba
M. Assadi- Porter. Nitrogen recycling via gut symbionts increases
in ground squirrels over the hibernation season. Science, 2022;
375 (6579): 460 DOI: 10.1126/science.abh2950 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220127141503.htm

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