There is a whale that has been alive for more than two centuries. And it has things to teach us

Stopping aging is one of the objectives that a field of science has right now that is very focused, above all, on preventing diseases as serious as cancer that can be associated with being older. Now the secret does not seem to be in a hidden book, but on a bowhead whale what is one of the oldest known mammals with a life expectancy that exceeds 200 years.

A headache. This combination of size and longevity has been a problem for biologists for decades. Precisely, more cells (due to their size) and more time (due to their longevity), the greater the probability that one of those cells will accumulate mutations and turn into cancer, as happens in humans. However, this does not seem to affect the bowhead whale: it is not particularly prone to cancer.

This apparent contradiction is known like Peto’s paradox. And now, a team of scientists from the University of Rochester believes he has found the key to this resistance.

The importance. With the passage of time, humans accumulate different mutations in our cells that a priori They couldn’t be more important. The change of one nucleotide for another in a very complex sequence of a protein may not alter the resulting amino acid, and it is very common, since our ‘genetic photocopiers’ such as DNA polymerases they are not perfect and they make mistakes in their work when it comes to replicating DNA.

And it is precisely in these errors that the probability of suffering from a major disease such as cancer increases. Above all, it is worrying when these errors accumulate throughout life. This makes finding ‘the secret of eternal youth’ crucial for humans and the control of devastating diseases.

When we think about anti-aging we automatically imagine wrinkle-free skin, but beyond aesthetics, science is interested in how young the cells are. And this is where the question is that now focuses on the genome of these whales that seem to hold the key to understanding how to reverse our molecular aging.

The hypotheses. Why a whale has such a high life expectancy despite its size has led to different scenarios being considered. The first of them is that the whale can have extra defenses, as happens in elephants that have evolved to have extra copies of tumor suppressor genes, such as the TP53. Basically, they have more “police” monitoring the genome so that, the moment there is a cancer cell, it is eliminated by apoptosis.

But when researchers tested the whale’s cells, they got a major surprise. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic “hits” (what we can say are mutations) to undergo malignant transformation than human fibroblasts. That is, they are more likely to develop cancer compared to humans.

So how come they don’t develop cancer in the wild? If your cells are, in theory, more vulnerable, where’s the catch?

The repair. And the trick is not in have many police officers monitoring our cells to ‘kill’ those that get out of controlbut it is about having a big toolbox to fix everything that is not normal. It is something that the team led by Professor Vera Gorbunova discovered in the cells of the bowhead whale.

In this case, instead of eliminating damaged cells in a process called apoptosis, the whale had perfected the art of repairing them. Their cells showed an “enhanced” ability and fidelity to repair DNA double-strand breaks, which are the most dangerous type of genomic damage. This results in lower mutation rates than present in other mammalian cells.

A protein. The person responsible for this super repair is a protein called CIRBP (cold-inducible RNA binding protein). And the name is no coincidence. These types of animals spend their entire lives in the icy waters of the Arctic, and it seems essential to activate this repair system that is present 100 times more frequent in these animals than in humans.

And CIRBP seems a real swiss army knife of repair for everything it can do within the whale’s body. Something that can be summarized in the following points:

• It protects DNA from degradation so that it ‘holds up’ to being repaired.
• Reduces the formation of ‘micronuclei’, a clear sign of genomic instability and chromosomal damage.
• It increases the precision of DNA repair so that the genetic material ends up well assembled and without any type of error.

In short, we are talking about a conservative strategy of nature: instead of discarding cells that may still be useful, the whale invests in meticulously repairing them. This not only prevents cancer, but also contributes to its exceptional longevity, as it keeps tissues functional for longer.

In humans. The question in this case is whether we can take advantage of this great repair capacity within our body. To do this, the research team introduced the whale protein CIRBP into human cells and the result was a success: the protein improved the efficiency of DNA repair in our own cells.

But the star experiment was done with fruit flies. In this case, the researchers engineered the flies to overexpress the CIRBP protein (both the human and whale versions) and the results showed a much longer lifespan and greater resistance to the ionizing radiation that destroys our DNA.

The next step is now to breed mice with enhanced levels of CIRBP to see if it also makes them live longer, and who knows if it finally somehow becomes a drug that could be very useful especially for those people who are more likely to suffer from cancer.

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