Lifespan of mammals has been linked to the frequency of mutations in their DNA

(ORDO NEWS) — In a first-of-its-kind study, scientists compared the frequency of DNA mutations in the cells of various mammalian species, from rabbit to giraffe and, of course, humans.

The results of the work confirm a long-standing theory that links mutation frequency with life expectancy, aging and the development of cancer.

Genetic changes, known as somatic mutations, occur in all somatic (i.e., all but the sex) cells of an organism throughout its lifetime.

Lifespan of mammals has been linked to the frequency of mutations in their DNA 1 1

This is a natural process in which, for example, human somatic cells acquire from 20 to 50 mutations per year. Most of these mutations are harmless because they do not affect vital parts of DNA, but some of them can disrupt the normal functioning of the cell and even contribute to its transformation into cancer.

Since the 1950s, a number of scientists have assumed that these mutations can play a significant role in the aging of cells and the whole organism. However, the difficulty of observing somatic mutations in individual cells made it difficult to explore this possibility.

Only in the last few years, technological advances in the reproduction and sequencing of single cells of the body has made it possible to observe such genetic changes, which means that the answer to this long-standing question can finally be found.

Another question from the last century is Peto’s paradox. It was formulated by the English statistician and epidemiologist Richard Peto in 1977 and is as follows: if cancer develops from single cells, species with larger bodies (and therefore more cells) should theoretically have a higher risk of developing cancer.

Nevertheless, it has been repeatedly shown that the incidence of cancer in animals does not depend on the size of their body.

The paradox can have several resolutions. For example, it is most likely that large-bodied animal species have simply evolved better cellular mechanisms to prevent the development of cancer. But it is still unclear whether one of these mechanisms is a decrease in the accumulation of genetic changes in their tissues.

A group of scientists from the UK set out to test these theories by studying somatic mutations in 16 mammalian species spanning a wide range of lifespans and body weights. Species studied include humans, monkeys, mice, cats, lions, tigers, dogs, giraffes, and long-lived naked mole rats known to be highly resistant to cancer.

The authors of the work found that somatic mutations accumulate linearly over time, they are caused by similar mechanisms in all studied species, including humans, despite their significant differences.

At the same time, the frequency of somatic mutations decreases as the lifespan of each species increases: therefore, DNA mutations play an important role in the aging of the organism.

Lifespan of mammals has been linked to the frequency of mutations in their DNA 2Linear regression of somatic replacement burden (number of mutations in somatic cells) versus individual age in dogs, humans, mice, and naked mole rats. The shaded areas represent the 95% confidence intervals of the regression line

“The discovery of a similar pattern of genetic changes in animals as dissimilar as mice and tigers was unexpected. But the most exciting aspect of the study was the discovery that lifespan is inversely related to the frequency of somatic mutations.

This suggests that somatic mutations may play some role in aging, although alternative explanations are possible.

Over the next few years, it will be interesting to expand these studies to include even more diverse species such as insects or plants,” explains Dr. Alex Cagan of the Sanger Institute (UK) and first author of the study.

However, Peto’s paradox still remained unresolved. After taking into account life expectancy, the authors did not reveal a significant relationship between the frequency of somatic mutations and body weight. This means that other factors must influence the ability of larger animals to reduce the risk of developing cancer.

Lifespan of mammals has been linked to the frequency of mutations in their DNA 3Dependence of the frequency of mutations per year on life expectancy (s) and on the logarithm of the adult body weight (e) for all studied mammals

According to the authors, the adjustment of mutations seems to be a very elegant way to control the incidence of cancer, but evolution, apparently, did not follow this path, but came up with a different solution to the problem.

Interestingly, despite the huge differences in lifespan and body weight between the 16 species studied, the differences in the number of somatic mutations acquired during the life of each animal were relatively small.

On average, a giraffe is 40,000 times larger than a mouse, and a human lives 30 times longer, but the difference in the number of somatic mutations per cell at the end of life between these three species is “only” three times.

This means that the diseases of old age can be very similar in a wide range of mammals, regardless of whether this old age begins at seven months or at 70 years.

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