Humans spend fortunes on lotions, supplements and fads that promise to slow aging. The bowhead whale, a giant denizen of Arctic waters, has no such anxieties. It lives for centuries, rarely succumbing to cancer or other ailments that cut our lives short.
How does such a massive creature — weighing some 80 tonnes, with billions upon billions of cells — stay healthy for so long? Could its biology offer humans clues on how to defy age itself?
Scientists at the University of Rochester in New York think so. In a study published in Nature, they have identified a protein known as CIRBP that appears to play a key role in prolonging the whale’s life. The molecule — short for “cold-inducible RNA-binding protein” — helps repair damaged DNA, a defence that fends off cancer.
The whales can reach up to 20m in length
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When the researchers added the whale version of CIRBP to human cells, they repaired broken DNA more accurately. In fruit flies, it even extended their lives.
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Professor Vera Gorbunova, who led the study, believes the results could point to a treatment that allows future generations “to live longer than the typical human lifespan”.
With some bowhead whales believed to be at least 250 years old, the species is the longest-lived mammal. “It’s a superstar of longevity research,” said Dr Alex Cagan, an evolutionary geneticist at the Wellcome Sanger Institute in the UK.
By studying the mammals, scientists hope to untangle a biological puzzle known as Peto’s paradox. Big animals, such as whales and elephants, should face higher cancer risks than small ones — simply because they have more cells dividing over longer lifespans. For some reason, or combination of reasons, they do not.
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Each cell division requires DNA to be copied and duplicated. In humans, that process inevitably introduces errors in the DNA code, or “oncogenic hits” — mutations that can trigger tumours.
Initially, Gorbunova and her colleagues hypothesised that the whales’ secret was that they could withstand large numbers of these hits without developing cancer. Their results, however, revealed something different: whale cells were accumulating far fewer cancer-causing mutations to start with.
Despite their size, the cancer risk among bowhead whales is lower than humans
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CIRBP appears to be central to that resilience. The protein helps fix the most perilous form of genetic damage, so-called double-strand breaks to the DNA double helix — the structure inside the cell that carries genetic information. Bowhead whale cells perform these repairs both more efficiently and more accurately than those of humans or mice. As a result, its DNA stays pristine for an unusually long time.
The strategy differs from that seen in elephants. The largest land mammal defies cancer by having numerous copies of so-called “tumour-suppressor” genes. These effectively kill off cells that have accumulated dangerous mutations.
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The whale, by contrast, pursues what the researchers call a “conservative” strategy: it keeps its DNA in good repair, stopping it from becoming corrupted in their first place.
Cagan said the findings were “intriguing”, adding: “It would be great to see them replicated by another lab just to increase our confidence. But overall, it’s a very compelling result.” The work “points the way towards new therapeutic angles that could be explored”, he said.
The clue to why the whales have so much CIRBP may lie in their very cold Arctic habitat. Production of the protein rises when temperatures fall. “If we just lower the temperature a few degrees, cells make more CIRBP,” said Andrei Seluanov, a co-author of the study.
That detail has sparked speculation. Scientists were already asking whether mild exposure to chilly temperatures could help protect humans from disease. If it does, could the human version of CIRBP play a role? “Lifestyle changes — things like taking cold showers — might contribute and might be worth exploring,” Gorbunova said.
Her team’s next steps will include testing whether CIRBP — or drugs that activate its production — reliably and safely improves DNA repair in smaller, shorter-lived mammals.
“There are different ways to improve genome maintenance. Here we learn there is one unique way that evolved in bowhead whales where they dramatically increase the levels of this protein,” she said. “Now we have to see if we can develop strategies to upregulate the same pathway in humans.”