[ A team of researchers dreams of anti-aging, disease-tempering
drugs—all inspired by bats. ]
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BATS COULD HOLD THE SECRET TO BETTER, LONGER HUMAN LIFE  
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Katherine J. Wu
November 8, 2023
The Atlantic
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_ A team of researchers dreams of anti-aging, disease-tempering
drugs—all inspired by bats. _

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In Linfa Wang’s ideal world, all humans would be just a bit more
bat-like.

Wang, a biochemist and zoonotic-disease expert at Duke-NUS Medical
School, in Singapore, has no illusions about people flapping about the
skies or echolocating to find the best burger in town. The point is
“not to _live _like a bat,” Wang told me, but to take
inspiration from their very weird physiology in order to boost the
quality, or even the length, of human life. They might not look it,
but bats, Wang said, are “the healthiest mammals on Earth.”

That thought might be tough to square with bats’ recent track
record. In the past three decades—from 1994, when Hendra virus
jumped to humans, to 2019, when SARS-CoV-2 emerged—at least half a
dozen of the most devastating viral epidemics known to have recently
leapt into people from wildlife have had their likeliest origins in
bats. But bats themselves rarely, if ever, seem to fall ill. Ebola
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and various coronaviruses don’t appear to trouble them; some bats
can survive encounters with rabies
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untreated in humans, has a near 100 percent fatality rate.
“They’ve evolved mechanisms to limit the damage of disease,”
says Emma Teeling, a bat biologist at University College Dublin, who
collaborates with Wang.

The creatures’ apparent ability to defy death goes even beyond that.
Some nectar-devouring species spend years spiking their blood-sugar
levels [[link removed]] high
enough
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send a human into a hyperglycemic coma—and yet, those bats never
seem to develop what we’d call diabetes. Others have been documented
surviving up to 41 years in the wild
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10 times as long as mammals of their size are generally expected to
live
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the while avoiding cancer
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fertility dips.

Wang and Teeling, along with several colleagues, were
recently awarded a $13 million grant
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Research Council to try to better understand the biology behind these
batty abilities—and how it might help other creatures. (And
they’re certainly not the only ones
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team, as he likes to cheerfully boast, has already put some of his
ideas to the test by genetically engineering a healthier, more
disease-tolerant “bat-mouse
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are still years away from creating any sort of bat _person_, but they
are confident that this line of thinking could one day inform new
treatments for humans—to combat diabetes, to temper infectious
diseases, maybe even to extend the life span.

The key to bats’ health seems to be flight, or at least the effects
that _evolving _flight has had on the bat body. Flight, for all its
perks, is one of the most energetically taxing
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options: When bats fly, their metabolism can rev up to 15 to 16 times
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their heart rate may soar above 1,000 beats per minute
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temperature can
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105 degrees Fahrenheit, effectively plunging the animals into an epic
fever state. Put all of that on virtually any other mammal, and its
body would likely be overwhelmed by the blaze of extreme inflammation,
the toxic by-products of their metabolism effectively rending cells
apart.

To cope with this self-destructive form of locomotion, bats have
evolved two essential safeguards. First, they are extraordinarily good
at maintaining bodily zen. Even when pushed into extreme forms of
exertion, bat bodies don’t get all that inflamed—maybe in part
because they lack
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of the molecular machinery that kicks those systems into gear. Which
means that bats simply rack up less damage
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get stressed. And for any damage that _does _occur, bats have a
second trick: Their cells appear to be unusually efficient at cleanup
and repair [[link removed]],
rapidly stitching back together bits of torn-up DNA.

Those strategies, Wang and Teeling told me, haven’t just made flight
a breeze for bats. They also mitigate other types of bodily harm.
Cancer tends to unfurl after errors appear in particular parts of our
genetic code. And, molecularly speaking, aging is basically what
happens to the body as it accumulates a lifetime of cellular wear and
tear. In a sense, stress is simply stress: The root causes of these
chronic health issues overlap with the greatest taxes of flight. So
the solutions that keep a bat body running smoothly in the air can
address problems throughout its lifetime. While humans get worse at
repairing damage with age, bats’ ability improves, Teeling told me.

All of this can also help explain why bats are such hospitable hosts
for pathogens that can kill us. Many of the most dangerous cases of
infectious disease are driven by the body’s overzealous inflammatory
response; that reaction can pose a greater threat than any damage that
a pathogen itself might do to cells. Many of our defenses are like
bombs set off on our home turf—capable of killing invaders, yes, but
at great cost to us. Bats have such a high threshold for igniting
inflammation that many viruses seem able to inhabit their tissues
without setting off that degree of destruction. In laboratory
experiments, bats have been dosed with so much virus that their
tissues end up chock-full—clocking some 10 million units of Ebola
virus per milliliter of serum, or 10 million units of the MERS
coronavirus per gram of lung——and researchers were still unable
to discern serious problems with the bats’ health
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viruses have, in effect, struck “an immunological detente,” says
Tony Schountz, a bat immunologist at Colorado State University.

Such astronomical levels of virus aren’t a bat’s preferred state.
Bat bodies also happen to be very good at tamping down viral
replication
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front. Part of the reason seems to be that, in certain bat species’
bodies, parts of their antiviral defense system “are always on,”
Wang told me. “I call them ‘battle ready.’” So when a
pathogen _does _appear, it knocks up against a host that is already
teeming with powerful proteins, ready-made to
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viral life cycle, hindering the microbe from spinning out of control.

The catch here is that the viruses have wised up to bats’
tricks—and evolved to be more forceful as they attempt to infiltrate
and replicate inside of, and then spread between, those well-defended
cells. And that bat-caliber offense can be excessive in a human that
lacks the same shields, says Cara Brook, a disease ecologist at the
University of Chicago. That might help explain why so many bat
viruses
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us so hard [[link removed]]..
Couple that show of force with our difficulties reining in our own
inflammation, and what might have been a trivial infection for a bat
can turn into utter chaos for a person.

One of Wang’s primary ideas for dealing with this kind of
host-pathogen mismatch is to use drugs to make our inflammatory
responses a bit more muted—that is, a bit more bat-like. That option
is especially intriguing, he told me, because it could also lower the
risk of autoimmunity, maybe even forestall aging or certain kinds of
chronic metabolic disease. His bat-mouse, which was engineered to
express a particular inflammation-suppressing bat gene
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that principle, and it seemed to fare better against flu, SARS-CoV-2,
even gout crystals.

But the idea of muffling inflammation isn’t exactly new: Our medical
armamentarium has included steroids and other immune-system-modulating
drugs for decades. All have their limits and their drawbacks, and a
treatment specifically inspired by bats would likely be subject to the
same caveats, says Arinjay Banerjee, a virologist and bat immunologist
at the University of Saskatchewan. Inflammation, as damaging as it can
be, is an essential defense. Any drug that modifies it—especially
one taken long-term—must avoid the hurt of _too much_ while
skirting the risk of _not enough_. And ultimately, humans just
aren’t bats. Plop a bat’s defense into a human body, and it might
not work in the way researchers expect, says Hannah Frank, a bat
immunologist at Tulane University. To truly see bat-like benefits in
people, chances are, we’d need more than one treatment turning more
than one physiological dial, Banerjee told me.

As much as researchers are learning about bats, the gaps in their
knowledge are still huge. What’s observed in one of the more than
1,400 species of bats may not hold true for another. Plus, bat
physiology is distinct enough from ours that no one really can
precisely say what optimal health for them looks like, Frank told me.
Although bats rarely die from their viruses, those infections may be
still taking a toll in ways that researchers have yet to appreciate,
Brook told me. Bats aren’t the only intriguing virus-carriers,
either. Rodents, too, haul around a lot of deadly pathogens
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Schountz points out. Nor are they the only mammals that live at
extremes. Naked mole rats withstand low-oxygen conditions underground;
seals must cope with organ-crushing pressures when they dive. Like
flight, those adaptations may have rejiggered immunity in yet untold
ways.

Certainly, though, bats have more to offer us than many people give
them credit for. In the aftermath of a Hendra virus outbreak in
Australia, years ago, “we even had a politician say, _Let’s bomb
the bats_
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Wang told me. The start of the coronavirus pandemic
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bat cullings; some animals were even reportedly burned out of roosts.
“I still don’t want a bat as a pet,” Wang told me. But if his
findings keep panning out, maybe someday people will associate bats
less with the diseases we don’t want to get from them, and more with
the healthy traits we do.

_Katherine J. Wu
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writer at The Atlantic._

* bats
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* medical information
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* aging
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* disease
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