Greenland sharks can live for centuries. We're finally learning their genetic tricks.
A first-ever analysis of the whole Greenland shark genome gives researchers a couple of clues to their longevity.
For humans, puberty hits after around a decade. But Greenland sharks have to wait well over 100 years. A century-long childhood might seem like science fiction, but Greenland sharks are the longest-living vertebrate on Earth, with lifespans thought to stretch to around 400 years. These fish spend centuries diving deep into frigid Arctic and Northern Atlantic waters, where they reach massive sizes by growing roughly a centimeter a year. The largest fully grown Greenland sharks can be longer than a Toyota Prius and weigh over 2,000 lbs.
(Is Iceland Really Green and Greenland Really Icy?)
Normally, an animal can’t grow so old. Over time, declining bodily functions and illnesses like cancer accumulate and take their toll. Yet the Greenland shark seems to defy this pattern, meaning it must have evolved genetic tools to stave off age-related diseases.
Recently, scientists have gotten some new genetic clues to their longevity. And while the new findings won’t translate to humans living to age 400, they are giving scientists tantalizing blueprints for how we might maintain health longer into our lives.
How to catch an enormous Greenland shark
In 2021, Arne Sahm decided to hunt for clues behind the sharks’ long life; not just to learn about the shark, but also to potentially compare them to the biology of other long-lived animals, like the naked mole rat.
“It's good to learn whether there are some common tricks of evolution to make very long-lived species even more long-lived,” says Sahm, a bioinformatician at the Leibniz Institute on Aging – Fritz Lipmann Institute in Germany.
(Widely set eyes give hammerhead sharks exceptional binocular vision)
He first needed a complete Greenland shark genome, which scientists didn't have before this work. To assemble the genome, first he needed to collect fresh samples from sharks, and catching a one-ton fish that can dive to depths of up to 7,000 feet is no small venture.
“You put 10 hooks on a long line,” says John Steffensen, a marine biologist at the University of Copenhagen in Denmark who worked with Sahm on the project, and has spent the last two decades catching these sharks for research. “They’re called shark hooks, they’re huge.” Onto those hooks goes chunks of stinky, rotten meat. A combination of heavy-duty ropes and chains lower the smelly snack down hundreds of feet, then haul it back up with a shark, or possibly multiple, in tow.
For Sahm’s research, Steffensen and other fishers caught sharks in the southern fjords of Greenland and sent the team brain samples. Researchers then extracted DNA from the samples to compile and inspect the sharks’ genome. They published their findings on a preprint server in September.
Two genetic clues point to the source of the sharks’ long lives
If a genome were a book of instructions, DNA would be the words and genes would be paragraphs. For the first time, the team put together the Greenland sharks’ entire book –– their chromosomal genome. They found the book is about twice as thick as a human’s, clocking in at 22,634 genes and around 6.45 billion base pairs. Base pairs form the rungs of a DNA strand’s double helix structure—the individual letters on a ‘page’ of DNA.
Once they had the completed genome, the team began to look for clues behind the sharks’ extreme lifespan. One element that stood out was a high amount of “jumping genes,” or transposons. Most organisms, including humans, have transposons: genes that duplicate themselves into a new section of a genetic sequence. They can introduce genetic diversity, but can also be harmful if the genes’ new placement disrupts the rest of a sequence. It’s like copying and pasting a phrase from somewhere else into the middle of a sentence, rendering it nonsensical, Sahm says.
But these transposons might play a more beneficial role in the Greenland shark. Many of the Greenland shark’s duplications included genes that were linked to DNA repair. So instead of creating a disruption, they may have created additional helpful genes, which could hypothetically slow down aging. If DNA is left damaged, it can contribute to problems within cells, including cancer. Researchers think the better a genome is maintained, the longer lifespan an organism could have.
(These sharks have rare earth metals in their organs. Is your old cell phone the culprit?)
A gene called TP53 also caught the teams’ attention. Heralded as the ‘guardian of the genome,’ TP53 is vital for cancer prevention. Many animals have it, including humans, elephants and whales. TP53 contains instructions for the protein p53, which aids in tumor suppression and DNA repair. It works by either stopping cells with damaged DNA from dividing further until it’s repaired, or causing them to die. That ensures the cell’s growth doesn’t snowball uncontrollably, becoming a tumor.
In Greenland sharks, a portion of its TP53 gene sequence is altered from how it typically functions in other animals. Using an AI model, the researchers predicted that the mutation could impact p53’s structure and how it handles DNA repair, possibly leading to a longer life. But Sahm notes these are only predictions—to further understand the alteration, they would need to experiment with it in cells in the lab.
How these insights, could, one day aid human health
The keys to a Greenland shark’s long life can help scientists understand longevity in other animals and could be beneficial to humans, too. But it isn’t going to help us live for centuries.
Sharks are too distant from humans and our systems are too different to make direct comparisons, Sahm says. Instead of providing a proverbial fountain of youth, the shark’s genome adds to other genomic data of long-lived animals. Scientists can make comparisons between those animals and humans to learn more about the aging process. For example, they can look for genes present in long-lived animals and absent in short-lived ones that could aid in staving off age-related diseases.
“The goal isn’t to make people live longer, the goal is to keep people healthier for longer,” says Paul Robbins, a molecular biologist at the University of Minnesota who was not involved with the study. Human longevity research mainly aims to improve people’s healthspans, the length of time someone spends in good health throughout their life. For example, one aspect of longevity research is how to balance long life with cancer prevention. Because there are some overlaps in our longevity-related genes –– like the importance of TP53, for example –– the shark’s genome could help reveal targets for developing healthspan therapies, like pharmaceuticals or gene therapies, Robbins says.
(It's not your life span you need to worry about. It's your health span.)
And because there are other animals studied for longevity, the results can help inform that research as well, Bodnar adds. For example, scientists can compare the Greenland shark to short-lived species like mice to look for differences. On the flip side, their genome can be compared to other sharks, or to other long-lived marine species like the bowhead whale, to look for similarities.
The new shark genome is “a wonderful tool to have in our toolkit,” says Andrea Bodnar, a cell biologist who is the Science Director at the Gloucester Marine Genomics Institute in Massachusetts who was not involved in the research. Bodnar studies longevity in marine animals, including the 200-year-old red sea urchin. “Each of these long-lived species has really come up with different solutions to achieve healthy aging and cancer resistance.”
More studies are needed to confirm the function of the proteins found in the Greenland shark’s genome. Looking at gene expression would be one next step, which can be done using cell cultures or by inserting genes in other model animals.
“It’s fantastic to have a genome, it's an essential resource for future studies,” Bodnar says. “But it really is just the beginning.”
