Clues to longevity may reside in the genomes of long-lived bats
Scientists are finding that bat genes involved in viral interactions also play a role in longevity
University of California - Berkeley
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This longeared bat, Myotis evotis, was captured in Arizona by researchers from UC Berkeley and the University of Arizona. The scientists took tissue samples from the wings before releasing it and used the samples to sequence the bat's genome and to establish cell cultures for study.
view moreCredit: Elise Lauterbur
The secret to a long life may lie in the genomes of the longest-lived mammals for their size: bats.
That idea captivated Juan Manuel Vazquez when he was a graduate student at the University of Chicago, but at the time he couldn’t find any good, published information on bat genomes to provide clues. Once he became a UC Berkeley postdoctoral fellow in 2020, however, he unleashed his passion and began scouring the Western U.S. for bat species that could provide tissue samples and DNA to sequence.
Enlisting the help of Berkeley undergraduates, he traveled around the West erecting mist nets over streams, ponds and rivers at night to capture, biopsy and release as many species of bats as he could. He focused on those in the genus Myotis, which contains the bat with the longest lifetime — a Brandt’s myotis, Myotis brandtii. One individual was banded in Europe and recaptured 50 years later.
In a new paper appearing this week in the journal Nature, Vazquez and colleagues report the first analysis of eight Myotis genomes and the discovery of a close link between the animal’s longevity and its immune system — longer-lived bats had higher levels of cancer-fighting genes.
The findings suggest that an immune system able to mount an overwhelming attack against infectious organisms and cancer may be integral to a long lifespan. The overlap between genes involved in aging and those involved in fighting disease also means that understanding one will help scientists understand the other.
“Bats evolved to live for a long time without getting diseases, which suggests that we don't necessarily need to look at diseases of aging and diseases of infection as completely separate fields,” Vazquez said. “We can look at these bats and try to understand how, in the same way you can improve your immune system to fight off viruses, maybe you can improve your immune system so it doesn't decline in old age. Or maybe bats can help us find ways to fight off tumors so our immune system doesn’t get tired, and that can also help us deal with other stresses of life and not exhaust our immunity.”
For the study, Vazquez cultured cells he biopsied from the wings of the bats. (He currently has cell cultures from 259 individuals representing 32 species.) When he treated cultured bat cells with toxic chemicals, he found an unusual response: for the longest-lived bat in his sample, the widespread little brown bat (Myotis lucifugus), the toxin didn’t trigger activation of genes for DNA repair proteins, but rather up-regulated genes promoting cell death.
“We found the literal opposite of what we expected if you treat the bats with a lethal dose of this chemical,” he said. “The longest-lived bat in North America decides ‘I can't save this ship’ and immediately switches gears to prioritize killing off the cells that are damaged. The elephant, another cancer-resistant species that is long-lived, has the exact same strategy — if you can't save the cell, kill the cell.”
The discovery is a heads-up that clues to longevity can be gleaned from understanding the different ways animals deal with disease, said Peter Sudmant, a Berkeley associate professor of integrative biology who studies the genes involved in aging and longevity.
“By looking across the diversity of life and the remarkable longevities of different species, we hope we can better understand the interplay between DNA damage and the immune system to enable us to have full and healthy life spans,” he said.
“If you start looking at long-lived species like elephants, whales and bats, you start finding ways that nature has actually already resolved a lot of these problems in human health,” Vazquez added.
Longevity, an active lifestyle and an immune system on high alert
The bat lifestyle has been a big success since the group arose about 60 million years ago. Bats now comprise 20% of all mammalian species, live on all continents except Antarctica and occupy a wide range of ecological niches. Of the known 1,511 species, about 139 are in the Myotis genus, which is known for bats exhibiting an extreme range of lifespans. While Brandt’s myotis bats can live half a century, the black Myotis — Myotis nigricans, of South and Central America — lives a mere seven years. This is as if our close relative, Homo neanderthalensis, lived nine times longer than modern Homo sapiens, Vazquez said.
Despite bats’ evolutionary success, scientists were surprised to find that their immune systems are hyperactive, working overtime to suppress damaging inflammation from constant viral infections without actually becoming sick. As a result, healthy bats can host an amazing variety of viruses, some of which, like the cause of COVID-19, can spill over into human populations.
Some researchers have linked bats’ robust immune systems to their very active lifestyle. Vazquez likens bats’ nighttime patrols for bugs to running several ultramarathons every day.
“Bats have evolved this incredible fitness capacity, this incredible ability to deal with disease and this incredible ability to be able to prevent cancer,” he said. “That means that, by understanding how bats have evolved to do all these things that other mammals haven't, we can find completely new and unexpected ways of dealing with the normal things that cause human diseases.”
The new study provides tantalizing clues. Vazquez found that whenever he identified a bat gene linked to lifespan, his collaborator, Elise Lauterbur, then at the University of Arizona, had identified the same gene as one involved in the bat’s interaction with viruses.
“There is way more overlap than you would expect just by random chance between the genes that are associated with longevity and genes that are associated with viral interactions,” he said.
Another surprise was that Myotis bats have an enhanced abundance of genes that make proteins that interact with DNA viruses — viruses, like herpes, that encode their genes using DNA. These proteins can either promote infection or protect against it, such as by boosting expression of the antiviral hormone interferon.
“DNA viral interacting proteins were strongly enriched for selection in bats in contrast to most other mammals, where there is a very strong enrichment for selection for both DNA and RNA viral interacting proteins,” Sudmant said. Humans and other primates, on the other hand, tend to have more genes for proteins that interact with RNA viruses, like COVID and HIV, than DNA viruses.
This mismatch between bats and humans may be why viruses spilling over from bats into humans and causing zoonotic disease have wreaked such havoc in recent years.
“Humans and bats are badly suited to each other,” Vazquez said. “That is one of the reasons why we have to be careful working with bats — it's a two-way street for zoonoses. We don't want to give the bat something and we don't want to get something from the bat. That mismatch is definitely something we should look into more.”
While Vazquez continues to investigate the genetic control of longevity in cell culture in his new faculty position at Pennsylvania State University, Sudmant is more interested in the immune responses of these cells.
“One thing that I'm really excited about is the trade-off between how a bat protects itself by producing proteins that attack the genomes of viruses but also protects its own genome from being attacked by those proteins,” he said.
He currently has cell cultures from many species of primate in which he is studying the genetic basis of longevity and how that’s related to DNA repair genes.
In addition to Vazquez, Sudmant and Lauterbur, now at the University of Vermont, other co-authors of the paper include Lucie Etienne of the École Normale Supérieure in Lyon, France, and David Enard of the University of Arizona in Tucson. The work was funded by the National Institutes of Health and the National Science Foundation.
Journal
Nature
Subject of Research
Animals
Article Title
Insights into longevity and virus-driven adaptation from Myotis bat genomes
Article Publication Date
26-Aug-2026
Researchers taking tissue samples from bats captured for study and subsequently released.
Credit
Juan Manuel Vazquez
What if bats hold the secret to a long, healthy life?
New study in Nature reveals how bats evolved genes that drive longevity, immunity, and cancer resistance
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Elise Lauterbur is an assistant professor of evolutionary biology at the University of Vermont and co-lead author of the study.
view moreCredit: Joshua Defibaugh, University of Vermont
Bats are anomalies in the mammalian world—they fly, have long lifespans, and rarely get cancer. Scientists now suspect the bat immune system enables them to live longer without disease, according to a new study published today in Nature.
An international team led by researchers from the University of Vermont and Penn State University found that the key to the impressive lifespan of bats and their ability to resist cancer is embedded in their DNA––specifically, the way in which bats code genomic changes after exposure to pathogens in their environment.
“Pathogen adaption, longevity, and cancer resistance—they are fundamentally linked,” says Elise Lauterbur, an assistant professor of evolutionary biology at the University of Vermont and co-lead author of the study. “Many of the genes that have adapted to viruses in bats are genes that are also involved in longevity and cancer resistance.”
By analyzing the bat genome and experimenting on cultivated cells to mimic their response to disease, the researchers identified where in the distant past eight species of Myotis—one of the largest groups of bats and found nearly everywhere except Antarctica—encountered pathogens and how it influenced their evolution. The team screened the genome for positive selection, in this case, adaptation to viruses, to pinpoint structural changes such as gene duplication or deletion, and found key differences in the way bats have adapted to DNA and RNA viruses from humans and other primates.
While humans show positive selection for proteins that interact with RNA viruses such as SARS-CoV-2 and Influenza, bats have an outsized selection for proteins that react to DNA viruses such hepatitis B and herpes viruses. This suggests a mismatch between humans and bats that can leave both species vulnerable to potential spillover of disease. Curiously, the team also discovered that bats exhibit a unique gene copy mechanism for DNA-repair—a process essential for longevity and resistance to age-related diseases such as cancer.
“One of the things that copy number variation allows is for diversification of the function of the gene,” Lauterbur explains.
Most of the time when coding changes occur it breaks rather than shifting to a new function. Copy number variation allows you to diversify, says Lauterbur. “So potentially, you now have two things you are good at instead of one.”
Assembling the bat genomes
This boosted immune defense strategy may allow bats to respond to multiple viruses or promote longevity using new pathways. The researchers built the first near-complete genomes for eight different Myotis bats to look for clues into how disease resistance played a role.
They collected tissue from Myotis bats in the American West using a novel sampling approach developed by biologist Juan Manuel “Manny” Vazquez, an assistant professor at Penn State University and co-lead author of the study. Instead of harvesting organ tissue, the scientists biopsied tiny circular patches from the wings akin to an ear piercing. Vazquez then used the tissue to grow cell lines and build genomes for the eight species. The approach unlocks new methods for scientists to study animals across their lifespan.
“Here is a way to do science for any animal on earth that doesn’t require killing the animal and is in fact compatible with better science,” Vazquez says.
This was especially important given the sample population includes Myotis lucifugus or little brown bats—North America’s longest living bat species and the one affected most by a deadly fungal infection called white nose syndrome.
Why examine bats in the first place?
Bats are among the most diverse mammalian species—second only to rodents—and live nearly everywhere and eat nearly everything. Bats can also live an extremely long time for their size—think decades rather than years.
“If you look at two bats, the same size, one lives 3 years the other lives 30 years and they are very closely related, like humans and Neanderthals, you can essentially find a very small number of genetic changes that leads to a very big change in their lifespan,” Vazquez explains. “And that is kind of the Holy Grail for evolutionary medicine.”
While scientists have long studied rodents, bats receive less attention. The authors wondered what if bats could provide new insights for human health because they have already evolved longer lifespans? Could the development of flight have propelled the diversity of bats around the world and shifted the evolutionary trade-offs from escaping predators to escaping disease?
Lauterbur studies how species evolve to environmental threats such as pathogens and focuses on disease resistance. Vazquez sequences genomes for insights into aging and age-related diseases. When they both pored over the results they marveled over the genetic changes—one seeing aging genes, the other seeing genes associated with disease.
“These are often studied as separate biological problems, Lauterbur says. “But our results suggest that evolution may be shaping them together.”
Potential pathways for cancer resistance
The research team homed in on a specific immune gene called protein kinease r (PRK) found in every mammal to understand what made the Myotis bats antiviral response so different.
“In every single other mammal that has been looked at, there is one copy of this gene,” Lauterbur explains. “That means there is some important pressure keeping it at one copy. In our very special Myotis bats, there are two copies—or so we thought.”
When she teased apart the genome, Lauterbur found some Myotis bats had one, two, or even three copies of PKR, suggesting additional copies have a protective effect that promote longevity. Collaborators conducted experiments on the various cell lines, splicing copies of PKR into different species and then introduced the cells with a pox virus to gauge their reaction and dosed the cells with chemotherapeutic drug to test how they tolerate and repair damage. The team found little brown bats—the longest living bats of the group—responded differently at high doses where cell damage would most likely occur.
“The little brown bats start committing to kill off cells,” Vazquez says. “Our hypothesis is it’s dumping the cells that can’t be salvaged.”
This adaptation could be critical for curbing the spread of cancer. As organisms age and cellular processes decline, some particularly long-lived species have developed specialized responses from repairing damaged cells, isolating the damage, to throwing cells out upon damage detection.
“The bats seen to be really good at repairing and killing off the damaged cells,” Vazquez says.
While it may be too early to use the unique immune adaptations of bats to solve human pathology, some lessons may be particularly valuable.
“Everything is connected,” Vazquez says. “Everything uses the same shared set of biology. … We don’t have to treat all of these different problems as silos. We can now start focusing on systems like bats to understand how we can solve multiple human age-related diseases.”
Moving forward, Lauterbur wants to explore underappreciated adaptations such as changes in gene copy number, she says. “Those kinds of changes can give evolution additional ways to generate diversity and respond to changing environments, and I think we're only beginning to understand their importance.”
This study was funded by the National Science Foundation and the National Institutes of Health. Additional senior co-authors of the paper include Peter H Sudmant of the University of California, Berkeley; Lucie Etienne of the École Normale Supérieure in Lyon, France, and David Enard of the University of Arizona, Tucson. The DOI number for this paper is 10.1038/s41586-026-10932-7.
Journal
Nature
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Insights into longevity and virus-driven adaptation from Myotis bat genomes
Elise Lauterbur discusses her research on bats while holding a baby big brown bat at rehabilitation facility. (This species was not part of the study).
Elise Lauterbur studies how species evolve to environmental threats such as pathogens and focuses on disease resistance. The study found that bats have a unique way they code genetic changes after exposure to viral pathogens.
Bat munching on meal worm [VIDEO]
Bats have evolved to eat all kinds of diets including fruit, fish, insects, and blood. Bats serve an important ecosystem function as voracious insect predators, which can reduce the use of pesticides in communities. This video is of a baby big brown bat eating meal worms at a rehabilitation site in Vermont. It was not one of the species used in the study.
Credit
Joshua Defibaugh, University of Vermont
A researcher holds a tiny Myotis velifer or Cave Myotis bat during sampling. This species was included in the study.
A researcher in the study holds a tiny Myotis thysanodes of Fringed Myotis.
Credit
Elise Lauterbur
Manny Vazquez sequences genomes for insights into aging and age-related diseases. He is an assistant professor at Penn State University and co-lead author of the study. This photo is of him in the field.
Credit
Courtesy of Manny Vazquez
