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.
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.
Nature
Animals
Insights into longevity and virus-driven adaptation from Myotis bat genomes
26-Aug-2026