Aging leaves telltale marks on DNA, and for the first time, scientists have used those molecular signatures to create a model that predicts the age of sharks.
This tool, known as an epigenetic clock, was developed for the zebra shark (Stegostoma tigrinum) and could soon be expanded to more species, aiding in conservation efforts while also offering new clues about how aging works across the animal kingdom.
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“Sharks and rays are a really imperiled group,” said Samantha Bock, who conducted the study as a postdoctoral researcher at the University of Georgia and is now an assistant professor at Oklahoma State University. “A critical piece of understanding how a wild population is doing is knowing its age distribution, but we don’t have a reliable way to determine that for most sharks.”
The International Union for Conservation of Nature has estimated that 37% of all shark species are threatened with extinction, and overfishing is among the greatest threats.
Overfished populations tend to have different age structures than sustainably managed ones.
So, monitoring the age distribution of wild shark populations can help wildlife managers assess whether pressure from fisheries in a given region is sustainable.
Unfortunately, the traditional aging methods used for sharks are unreliable.
Using the shark’s size as a proxy is a common tactic, but this only works up to a certain age.
Counting the rings on its vertebrae, just like counting the rings on a tree stump, is potentially more accurate, but this method is imprecise and doesn’t work for all species.
It is also lethal, so scientists are limited to measuring sharks that wash up on shore or are snagged as bycatch.
Instead, scientists are looking toward a noninvasive method: epigenetic clocks.
These models, which predict an animal’s age based on its DNA, have been used across over 185 species of mammals, as well as a few birds, a reptile and several bony fish.
“If you dial it back to a 30,000-foot view, we know that all vertebrate organisms age. And that aging seems to follow similar patterns in different organisms, which suggests that maybe these are actually shared processes that can be detected in the genome,” said Gavin Naylor, director of the Florida Program for Shark Research at the Florida Museum of Natural History.
Epigenetic clocks work by using chemical marks that show up on certain sections of an organism’s DNA.
Chemicals known as methyl groups (a carbon group bonded to three hydrogen atoms) attach to cytosine bases in the DNA strand.
If this happens in just the right way, it can flip some genes on and off, instructing the cells how to behave without changing the underlying DNA.
Organisms typically lose methyl tags across their genome as they age, but some specific regions gain these tags over time.
Sharks remain a missing and critical addition to the development of epigenetic clocks across the animal kingdom.
A previous study on lemon sharks provided evidence of methylation patterns, but in order to calibrate an epigenetic clock, scientists must be able to map the sites onto a reference genome, which the lemon shark lacks.
In this study, scientists sequenced the genome of a zebra shark and identified a group of animals with known ages to develop the model.
Given the drawbacks of existing aging methods, researchers instead relied on aquariums, where resident sharks are often accompanied by a documented birth date and life history.
The zebra shark was both a charismatic and practical choice for the study. While young, these sharks sport black and white stripes, giving them a “zebralike” appearance.
They gain long ridges along their backs as they grow up to 8 to 10 feet in length. In the process, their stripes divide into dark spots speckling their yellow-brown skin, more akin to a leopard.
In the wild, these spots serve as camouflage for adults as they prowl the floor of the Indo-Pacific Ocean, squirming through reefs and sucking up mollusks, small bony fish, sea snakes and other prey hiding in crevices.
Researchers collected blood samples from 51 zebra sharks of varying ages that were born and raised in aquariums. Using a known zebra shark genome as a reference, the scientists aligned the DNA sequences from their samples to see the sites where chemical tags were accumulating on the DNA.
By sampling sharks of different ages, scientists could see how the patterns of chemical tagging increased or decreased over a shark’s lifetime.
Scientists needed the shark’s genome to create the epigenetic clock, but looking for patterns across the zebra shark’s roughly 3.7 billion base pairs would have been cost-prohibitive.
Fortunately, that’s unnecessary, as long as scientists pick a few sites that have reliable patterns of methylation over time.
“We were sequencing the entire genome-wide epigenetic patterns, but that’s pretty expensive,” Bock said. “Accuracy and number of sites have this push-and-pull trade-off. The more sites that you put into the model, the more accurate it is and the more it costs. Our goal was to make this feasible for others to use it.”
Scientists were able to narrow their scope to a subset of less than 100 sites that displayed the strongest trends with aging. From these sites, they developed a model that allows them to plug in a sample of zebra shark DNA and predict its age to an accuracy of within two years.
The model worked across age groups, although it was more accurate for younger animals whose methylation changes tend to be more pronounced.
Ultimately, scientists hope fellow researchers and conservation managers can use the model on wild zebra sharks, but comparing aquarium animals with wildlife does pose a challenge.
An epigenetic clock tells a deeper story than simple chronological time. The model can reveal the underlying biological age, which can be sped up due to stress, disease or environmental pressures.
Two organisms born in the same year might have very different biological ages depending on their lifestyles.
An aquarium animal accustomed to free meals and a lack of predators might display a different age on the cellular level compared with a wild-born shark facing a lack of food, habitat loss or other pressures.
To test the extent to which this might be a problem, the researchers also sequenced DNA from 19 zebra sharks that were born in the wild but live in aquariums today.
Because they don’t know the birth date of these sharks, scientists used size and the number of years since the animal was brought to the aquarium to determine its minimum age.
When using these ages as a comparison, the epigenetic clock was able to predict the shark’s age to an accuracy of three to four years. The model was still effective, but it was not quite as accurate as when looking at aquarium-born animals alone.
“I’m cautiously optimistic we’re able to predict ages of wild individuals,” Bock said. “There are ways that we can improve our model with more research, but overall, this study shows that these animals do display these patterns.”
Now that they’ve found the sites and genetic markers related to aging in zebra sharks, researchers can repeat their study and the resulting patterns with other shark species commonly found in aquariums. If these patterns match up across different species, scientists may eventually uncover a set of “universal markers” that work across all sharks.
“Scientists have already identified sites in mammalian genomes that predict age. These same sites apply to many different species of mammals, whether you’re looking at a mouse, a human or a monkey. The idea is that if you can do that in mammals, you could also do that in other groups,” Bock said.
This research also has scientists looking beyond sharks to a universal understanding of aging in large swaths of life on Earth. Sharks occupy an essential evolutionary position, having diverged from the rest of vertebrates some 400 million years ago. If similar aging patterns exist across all sharks, it would suggest that this way of aging is potentially an ancestral process in all vertebrates.
“This becomes about more than just sharks,” Naylor said. “We are breaking biology down into its simplest parts and putting it back together to understand how it works. If we understand how things work at a basic level, we can start to ask bigger questions.”