The bowhead whale is one of the largest and longest-lived mammals in the world, with a life expectancy that could even exceed 200 years. Why? An international scientific team points out that this remarkable longevity could be due to a greater capacity to repair mutations in the ADN.
Specifically, the work suggests that a longevity response lies in a protein called CIRBP. It plays a key role in repairing double-strand breaks in DNA, a type of genetic damage that can cause disease and shorten lifespan in various species, including humans.
Researchers found that bowhead whales have much higher levels of CIRBP than other mammals. The findings, while still very early, offer a new clue about how humans could one day improve DNA repair, better resist cancer and slow the effects of aging.
The details are published in the journal Nature, in an article led by Jan Vijg and Vera Gorbunova, from the Albert Einstein College of Medicine and the University of Rochester, in New York, respectively.
The “multistage model of cancer” is a widely accepted framework that explains how normal cells do not become cancerous in a single step, Gorbunova details. Cancer develops after multiple genetic mutations accumulate in key genes that control cell growth, division, and DNA repair.
Given this multistage model, one would expect that animals with more cells and a longer lifespan would accumulate more mutations and therefore face a higher risk of cancer, but that is not what is observed. This enigma is known as Peto’s paradox, recalls a statement from Rochester.
Large species do not have higher cancer rates than smaller ones, even though they have many more cells that divide for many more years. The paradox describes that larger ones, such as elephants and whales, must have evolved additional mechanisms to prevent or repair cancerous mutations.
The exact nature of these has baffled scientists.
To try to clarify this, the team investigated the probability that the cells of the bowhead whale mutated into cancer cells when an oncogenic stimulus (such as UV radiation) was applied.
The scientists saw, on the one hand, that whale cells actually need fewer mutations to become malignant than human fibroblasts.
And on the other hand, they discovered that the animal’s cells are less likely to accumulate oncogenic mutations from the beginning. In the observations, whale cells showed fewer mutations than human cells, suggesting that, despite being susceptible to DNA damage, it is repaired – which is why disease does not develop.
Does cold water help?
They identified above all a protein associated with this repair, CIRBP. They added it to cultures of human and fruit fly cells and, in both cases, DNA repair improved; in flies it even prolonged their lifespan.
The researchers also discovered that if the temperature is lowered just a few degrees, the cells produce more CIRBP protein. “What we still don’t know is what level of exposure to cold would be necessary to trigger that response in humans.” says Andrei Seluanov, also from Rochester.
The team is considering multiple ways to increase the protein in humans, but they are still hypotheses.