Volume 37, Issue 2, 2018

The Cavern of Youth

Bats could help unlock secrets of healthy aging

By Michelle Z. Donahue


There’s a rule of thumb about birthdays in the animal kingdom: The bigger you are, the more of them you celebrate. “Ancient” in the mouse world is about 4 years, while 200 years is perfectly normal for some whales.

Unless you’re a bat, and then you break a bunch of different rules about aging.

For starters, several species of bats can live up to 10 times longer than expected. New research into their genetics is underway to learn why and apply those lessons to aging in humans.

A greater mouse-eared bat (Myotis myotis) in hand.
Courtesy of Stephen Mahony

Mysterious Lifespans

Relative to their body size, only 19 mammal species live longer than humans, and 18 of those are bats (the other is the naked mole rat). Many Myotis can live more than 20 years, and a handful are known to live more than 30. Bats usually succumb to starvation, dehydration or predation well before that, but the bat that avoids these can have many happy returns; at least one Brandt’s bat (Myotis brandtii) is known to have lived for 41 years.

One reason for this lifespan could be how they maintain their chromosomes. In mammals, aging is linked to degraded ends of chromosomes, or telomeres. Usually, cells will self-destruct once the cell cannot properly rebuild these protective end caps, a process regulated by the protein telomerase. In humans, telomerase also plays an essential role in cell longevity—but it is also implicated in many age-related cancers, which “switch on” telomerase production to become immortal.

Many bats are curiously cancer-free. Emma Teeling, a bat researcher at University College Dublin, recently found that some Myotis bats may maintain their cells’ genetic integrity through genes that code for DNA repair instead of with telomerase.

Myotis bats also have hyperactive anti-inflammatory mechanisms that protect their bodies from the effects of stress that, in humans, are a prime driver of aging.

“We need to find ways to make our cells behave like bat cells,” Teeling says. “But first we need to know the differences between us and them before we can test for these differences.”

Mice Aren’t Humans, and Bats Aren’t Rats

Most human health studies are based on the humble lab rodent. With their ease of care and ample fecundity, mice and rats have been ideal study subjects.

In human health studies, many techniques that work to reduce the effects of aging on mice haven’t worked on people, says Jay Phelan, a biologist at UCLA who studies the evolution of aging. Humans aren’t simply blown-up versions of mice, and it’s high time for a new animal model to study aging, he says. Bats are an obvious choice, given their human-like lifespans, but they have one major downside: They don’t thrive under lab conditions.

One solution could be to use vampire bats, suggests Steven Austad. At the University of Alabama-Birmingham, Austad works with an assortment of long-lived animals to better understand what makes them tick. Though the vampire bat isn’t as long-lived as Brandt’s bat or other Myotis, they have a specialized diet that is relatively easy to maintain, and as a result, seem to do reasonably well in captivity.

That highlights the need to know more about the genetics of both long- and short-lived species, he says. “To understand the long-lived bats, you need something from the short-lived ones, so you can separate out ‘bat stuff’ from ‘longevity stuff,’” Austad says. That will help target areas of the genome involved in aspects of aging that most affect humans: declining memory, hearing and muscle tone; disease; and impacts of persistent inflammation.

Teeling and a consortium of other bat researchers have launched the Bat1K for just that reason. The initiative seeks to sequence the genomes of as many bat species as possible, with the goal of building a catalog that can be used to not only study how bats’ unique traits evolved, but also compare them more accurately with humans.

“The project has so much promise to advance our understanding not just about bats, but so many aspects of science, from human health to wildlife conservation,” adds BCI Chief Scientist Winifred Frick, who serves on the Bat1K steering committee. “It will also aid bat conservation efforts by enabling biodiversity assessment and informing various efforts to protect vulnerable bat populations around the world.”

Members of the Teeling Ageless research group and Bretagne Vivante
measuring and sampling bats in Brittany, France.
Courtesy of Stephen Mahony

Ticking Time Bombs

One issue that the genetics work will help reveal is which genes aren’t weeded out by a failure to reproduce. In organisms with long lifespans, natural selection can’t eliminate harmful genes that switch on in humans and bats later in life, usually after they’ve reproduced. Those genes get passed on. And they’re scattered throughout our DNA.

“The reason we don’t see a fountain of youth is because there’s not just one problem—we all carry these little ticking time bombs that manifest as aging, but we need to look at huge swaths of genomes to see which ones are most active in a bad way at advancing age,” Phelan says. Then by comparing what works in bats with a similar region in humans, researchers can investigate ways of slowing those effects.

But genetics are only part of what can be learned from bats, and Austad says that science is still catching up with a new generation of tech-forward tools that have given researchers almost more than they know what to do with.

For example, the study of metabolites, the molecules that fuel cellular processes, is still an emerging field; science has only identified about 10 percent of the several thousand metabolites that are thought to exist in the human body, Austad says. A better understanding of what’s common between bats and humans—metabolites, proteins and other compounds—as well as what’s unique to each, could help unlock their secrets and perhaps guide the development of new pharmaceuticals.

Or how to fight aging by getting better sleep.

“It’s increasingly clear that sleeping well is a key to lifelong health,” Austad says. “By looking at genes and more, we hope to see what’s novel—what bats have that we don’t.”

 

 

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