Wing DNA reveals how bats greatly outlive other small mammals

March 12, 2021

Long-lived bats have a "clock" to thank for their age. (G. Wilkinson, G. Jones, S. Puechmaille, M. Tschapka)

Scientists have developed a technique to predict the age of a bat from the state of its DNA in wing tissue samples, revealing potential explanations for why the flying mammals enjoy such unusually long lifespans.

The researchers discovered differences in DNA methylation — a mechanism that cells use to control whether a gene is switched on or off — between long-lived and short-lived bats. Many of these differences were related to genes involved in immunity or cancer suppression, the team reported March 12 in Nature Communications.

"If you look across all mammals, body size is a good predictor of lifespan; whales live longer than shrews," said Gerald Wilkinson, a biology professor at the University of Maryland and first author of the paper. "But If you control for body size, bats are super outliers and can live up to eight times as long as a similar-sized mammal."

A number of bat species can live for more than 30 years. 

"We tried to find samples from species which represented as many of those long-lived lineages as possible," Wilkinson said. He and his colleagues gathered tissue samples from 712 captive and wild bats with known ages representing 26 species. To find out whether they could accurately predict the bats' ages from their genetic material, the team measured DNA methylation at roughly 30,000 sites in bats' genomes. 

DNA methylation, which involves adding a kind of tag called a methyl group to the DNA molecule, can prevent a gene from being expressed. 

"Genes turn themselves on and off in different tissues at different times, and a lot of that control is due to methylation," Wilkinson said. "Over the lifespan in general, DNA methylation declines and one [consequence] of that is that there is uncontrolled gene expression."

Study coauthor Steve Horvath, a professor of human genetics and biostatistics at the University of California, Los Angeles, had previously developed a test called an epigenetic clock to measure aging in humans. Using a similar technique, Wilkinson, Horvath and their team found that DNA methylation levels at 162 sites were sufficient to accurately predict a bat's age to within a year across all 26 species. 

The researchers next investigated whether the rate at which methylation changes with age differed between three long-lived species — the greater horseshoe, common vampire and greater mouse-eared bats — and two with shorter lifespans, the velvety free-tailed and lesser long-nosed bats. To their surprise, the team found that some sites showed increased methylation over the lifespan, particularly in the short-lived species. 

"The long-lived species essentially show less change," Wilkinson said. "It suggests that stability in the epigenome is a good thing for living a long time."

When he and his team examined available genomes belonging to the long-lived bats and the velvety free-tailed bat, they found that the sites where methylation increased were linked to genes that are known to be involved in immunity or are frequently found mutated in human tumors.

Bats generally have low rates of cancer and their immune systems are able to cope with disease-causing viruses without the inflammatory responses that cause collateral damage like the excessive inflammatory reactions known as cytokine storms seen in some people with COVID-19, which can lead to organ failure and death.

"It certainly looks like there are some clues about how bats are able to live so long that can be uncovered by taking advantage of these methylation patterns," Wilkinson said.

The method Wilkinson and his team used to estimate the ages of individual bats will likely also work for other kinds of animals, he says. This will allow scientists to explore questions that would otherwise be difficult to answer. 

For bats, the epigenetic clock could allow researchers to investigate how DNA methylation patterns change when bats hibernate and whether this impacts their lifespan; whether female bats may cease reproducing well before they die, in contrast to most mammals other than humans; and why the animals are able to maintain their ability to find prey using echolocation into old age.

"Bats can live a long time and yet they rely on the ability to maintain their sensory abilities," Wilkinson said. "That means that they have some way of not losing high frequency hearing the way we do and other mammals do."

The study "DNA methylation predicts age and provides insight into exceptional longevity of bats," published March 12 in Nature Communications, was authored by Gerald S. Wilkinson and Danielle M. Adams, University of Maryland; Amin Haghani, Ake T. Lu, Joshua Zhang, Joseph Zoller, Caesar Z. Li and Steve Horvath, University of California, Los Angeles; Charles E. Breeze, Altius Institute for Biomedical Sciences; Bryan D. Arnold, Illinois College; Hope C. Ball, Lisa Noelle Cooper and Alexander V. Galazyuk, Northeast Ohio Medical University; Gerald Carter, The Ohio State University; Dina K. N. Dechmann, Max Planck Institute of Animal Behavior, University of Konstanz and Smithsonian Tropical Research Institute; Paolo Devanna, Max Planck Institute for Psycholinguistics; Nicolas J. Fasel, University of Lausanne; Linus Günther, Frieder Mayer and Martina Nagy, Leibniz-Institute for Evolution and Biodiversity Science; Edward Hurme, University of Maryland and University of Konstanz; Gareth Jones and Roger D. Ransome, University of Bristol; Mirjam Knörnschild, Smithsonian Tropical Research Institute and Leibniz-Institute for Evolution and Biodiversity Science; Ella Z. Lattenkamp, Max Planck Institute for Psycholinguistics and Ludwig Maximilians University Munich; Josephine A. Reinhardt, State University of New York, Geneseo; Rodrigo A. Medellin and Daniel Zamora-Mejías, Universidad Nacional Autónoma de México, Ciudad Universitaria; Brian Pope, Lubee Bat Conservancy; Megan L. Power and Emma C. Teeling, University College Dublin; Sonja C. Vernes, Max Planck Institute for Psycholinguistics, Donders Institute for Brain, Cognition and Behaviour and The University of St Andrews; and Paul A. Faure and Lucas J. Greville, McMaster University.

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