Mutations and life expectancy. Scientists can unravel a mystery from several decades ago

Depending on the species, animals usually die after reaching a certain number of mutations in their DNA. Findings about this should help unravel the mystery of the 1970s.

The authors of a new study devoted to this topic presented their conclusions on the pages of Nature† One of the main conclusions of the analyzes is that in long-lived mammals (eg humans), the so-called mutation clocks tick more slowly than in short-lived mammals such as mice. As a result, we usually cross the border at a later age than with rodents.

A paradox from the 1970s

This is partly related to the Peto paradox proposed by Richard Peto, who noted that there is no correlation between the size of a species and the incidence of cancer. In the 1970s, when Peto was dealing with this phenomenon, it was clear that animal cells accumulate mutations in their DNA over time. As their numbers increase, so does the risk of cancer cells. In theory, therefore, the longest-lived and largest animals in the world should be the most exposed to cancer risk.

However, reality does not confirm this: both short-lived and long-lived mammals accumulate a similar number of genetic mutations over their lifetime, but the latter do so at a much slower rate. It’s worth noting that the authors of the new study did not find a clear link between the body weight of animals and their mutation clocks. Therefore, the data collected cannot explain why large animals do not have a high cancer rate.

16 species covered by new research

As lead author Alex Cagan explains, a mammal can be estimated to be nearing the end of its life in the intended framework of its species when it has about 3,200 mutations in its colonic epithelial stem cells. Of course, crossing this line will not lead to sudden death, but the risk will continue to increase. In total, the researchers looked at genetic material from 16 species: humans, geese, cats, cows, dogs, ferrets, giraffes, porpoises, horses, lions, mice, sand charles, rabbits, rats, ring-tailed lemurs and tigers.

In this group, on average, people have the longest life (about 80 years), while the shortest – mice and rats (about 3-4 years). Members of the research team collected samples of each species in the mucosa of the small and large intestines. Previous findings related to our species suggested that mutations in these cells proceed at a rate consistent with the aging of the organism. The scientists first determined the total number of DNA mutations present in each sample and then estimated — taking into account the age of each individual — the rate at which these mutations appeared over their lifetime.

Different rates of accumulation of mutations in DNA

It turned out that, just like in humans, cells from other mammals also accumulate mutations at a constant rate, coinciding with the aging process. However, the pace of this phenomenon varied widely depending on the genre. For example, while in humans the number of new mutations was 47 per year, mice developed 796 during this period. On the other hand, as the life of a particular animal increased, the number of new mutations that appeared in it decreased every year. In practice, this means that the total number of end-of-life mutations for each individual was more or less the same, regardless of species origin.

The research team behind these disclosures now plans to broaden the scope of their activities. Accordingly, the authors intend to analyze other tissue types and focus on both vertebrates and invertebrates. More recently, Cagan and his collaborators gained access to tissue fragments from a Greenland shark that was about 100 years old. Death at this age – for this species – was quite early, because its representatives can live several times longer. Perhaps the tests performed will help clarify the circumstances under which later mutations appear in the DNA.

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