Cancer-resistant bowhead whales may hold key to understanding human longevity, scientists say

Findings underscore value of studying long-lived organisms to find novel longevity mechanisms for humans

Cancer-evading bowhead whales of the Arctic possess a highly specialised mechanism to protect their DNA, according to a new study that may lead to better ways of achieving longevity in humans.

Researchers, including those from the University of Rochester in New York, have found that bowhead whales, which can live for over two centuries, have an exceptional ability to repair their damaged DNA in a process that slows down their aging.

While previous studies have found biological mechanisms to avoid cancer in elephants, the new biological process found in the whales is unique, according to the scientists.

“By studying a mammal capable of maintaining its health and avoiding death from cancer for over two centuries, we are offered a unique glimpse behind the curtain of a global evolutionary experiment that tested more mechanisms affecting cancer and aging than humans could ever hope to approach,” scientists wrote in the yet-to-be peer-reviewed study.

The whale, which is one of the largest animals on Earth, grows to over 80 tonnes, and in spite of its very large number of cells, is not cancer-prone – presenting an example of an oddity that scientists call the Peto’s Paradox.

According to this paradox, even though large and long-lived animals such as elephants and bowheads have a large number of cells compared to humans, they do not experience a proportional increase in the incidence of cancer.

In the new study, posted as a preprint in the bioRxiv server, researchers found that the whales possess biological mechanisms that repair breaks in their DNA strands with “uniquely high efficiency and accuracy” compared to other mammals.

Scientists also found high levels of two proteins – CIRBP and RPA2 – in bowhead whales, which are known to increase the efficiency of DNA repair in human cells as well.

“We also present evidence that two proteins, RPA2 and CIRBP, are highly expressed in the bowhead relative to other mammals and contribute to more efficient and accurate [DNA] double strand break repair,” researchers wrote in the study.

The findings suggest that bowhead whales have evolved an accurate and efficient DNA repair process that preserves the integrity of their genome – a strategy that may be critical for their long and cancer-free lifespan.

This evolution of high levels of CIRBP protein expression in the whale is likely a product of the unique physiological stresses, including ultracold temperatures, that it must endure in the Arctic, scientists suspect.

Scientists draw comparison to this mechanism with whole body cryotherapy that is widely used in sports medicine to reduce inflammation and facilitate recovery after exercise or injury.

“While molecular mechanisms responsible for the beneficial effects of cryotherapy are largely unknown, we speculate that increased CIRBP expression may contribute to health benefits by facilitating DNA repair,” they write.

Based on the new study, researchers also speculate that the local delivery of variants of the CIRBP protein could hold promise as a strategy to improve tissue recovery from surgery or organ transplant.

However, there are currently no approved therapies to bolster DNA repair for the prevention of cancer or age-related decline.

But scientists believe future therapeutics based on increasing the activity or abundance of proteins like CIRBP or RPA2 may enable the treatment of genome instability as a modifiable disease risk factor of ageing and cancer.

They say the new study also highlights the value of studying such long-lived organisms to find novel longevity mechanisms for humans.