Bowhead whales can live over 200 years, making them the longest-lived mammals in the world. They are also largely resistant to cancer. But what is its secret? A study now shows that the concentration of a protein that repairs DNA damage is 100-fold increased in bowhead whales compared to humans. If the researchers transferred this whale protein to human cells, their genomes remained significantly more stable. It even extended the lifespan of fruit flies. The research team hopes to make the mechanisms behind the longevity of bowhead whales useful for human health in the future.
Cancer occurs when mutations accumulate in a cell and gradually change important genes that control, for example, cell growth, cell division and DNA repair. In humans, about five to seven of these harmful mutations are required before a cell becomes cancerous. The likelihood of cancer should actually be higher in large, long-lived animals such as bowhead whales. After all, with their body weight of over 80 tons, they have a huge number of cells, which also have a lot of time to accumulate mutations. But instead, the colossi appear to be largely resistant to cancer – and thus provide a treasure trove for cancer research.
Repair instead of eliminate
In order to uncover the secret of cancer resistance, a team led by Denis Firsanov from the University of Rochester in New York first examined whether the cells of bowhead whales could possibly accumulate more mutations before they degenerate. To do this, the researchers intentionally created several cancer-promoting mutations in tissue cultures from bowhead whales and humans. “Our hypothesis was that the cells of bowhead whales can accumulate six or seven damages before they degenerate,” says Firsanov’s colleague Vera Gorbunova.
But the results showed the opposite: “Surprisingly, bowhead whale fibroblasts required fewer oncogenic mutations for malignant transformation than human fibroblasts,” reports the team. But instead, another property ensured that mutations could not accumulate in the whales in the first place: “The cells of the bowhead whale showed improved repair capacity and accuracy for DNA double-strand breaks as well as lower mutation rates than the cells of other mammals,” the researchers found. “This strategy, which does not eliminate damaged cells but rather reliably repairs them, could contribute to the exceptional longevity and low cancer incidence in bowhead whales.”
A protein as a repair turbo
Using genomic data and molecular biology experiments, Firsanov and his colleagues investigated which cellular mechanisms are responsible for the bowhead whales’ extraordinary DNA repair ability. They particularly noticed a DNA repair protein called CIRBP, which is much more common in bowhead whales than in humans: “There were a few other DNA repair proteins that were present in slightly higher concentrations in bowhead whales, but CIRBP stood out because it was present in 100-fold higher concentrations,” says Gorbunova.
In further experiments, the researchers demonstrated that the CIRBP of bowhead whales also promotes genomic stability in human cell cultures and in tumors in mice. In addition, Firsanov and his team genetically manipulated fruit flies so that their cells produced particularly high levels of CIRBP, both in the human and in the bowhead whale variant. In fact, the fruit flies modified in this way lived a few days longer than their counterparts in the control group. They were also better able to resist radioactive radiation – further evidence that CIRBP plays a key role in DNA repair.
Transferable to humans?
From the researchers’ perspective, the discovery suggests that it could be possible to extend human lifespan with the help of CIRBP. “By studying the only warm-blooded mammal to survive humans, our work provides information about the mechanisms that enable such lifespan extension and highlights the importance of genome conservation for longevity,” says Gorbunova.
In further studies, the team would like to research which methods could be used. “Both increasing the body’s existing CIRBP activity and consuming more protein could work,” says Gorbunova. Another property of the CIRBP protein could possibly provide a starting point: at cooler temperatures, the cells produce more of the repair protein. “What we don’t yet know is how much cold exposure would be required to trigger this reaction in humans,” says Gorbunova.
Source: Denis Firsanov (University of Rochester, New York, USA) et al., Nature, doi: 10.1038/s41586-025-09694-5)