The older we get, the slower we mutate

This is a new stage in the long search for the causes of biological aging. New, but not quite so new: the study published in the specialist journal on April 13th Natureactually comes to the fore “a hypothesis put forward in 1952 by a future Nobel laureate, Peter Medawar [1915-1987]but so far unprovable: the idea that aging results, at least in part, from an inevitable accumulation of mutations in the genome of our cells, notes Hugo Aguilaniu, geneticist, director of the Serrapilheira Institute, a non-profit Brazilian foundation. And this accumulation would eventually bring about a critical state for the functioning of these cells. »

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The immense development of sequencing capacities has changed the situation. Thanks to this, British researchers were able to prove the reality of this phenomenon. Coordinated by the Wellcome Sanger Institute (UK), they counted DNA damage in cells from sixteen mammalian species covering a wide range of lifespans and body sizes: cat, dog, horse, cow, rabbit, ferret, mouse, rat, naked mole rat. Rats, giraffes, porpoises, lions, tigers, ring-tailed lemurs, black and white colobus monkeys and human species. Several people (56 in total) of different ages were analyzed for five of them.

As a result, longer-lived species acquire DNA mutations in their somatic (nonsex) cells more slowly than shorter-lived species. This observation partly explains the famous “Peto paradox”, named after the British epidemiologist Richard Peto, who formulated it in 1977. A whale or an elephant, for example, has many more cells and lives much longer than a mouse. The likelihood that one of their cells will experience mutations that lead to uncontrolled reproduction is therefore higher. Logically, these giants should have an increased risk of cancer. However, this is not the case.

Very clear differences

But how can we estimate the rate at which these mutations accumulate in the cells of each species? Difficult to follow an individual throughout his life! The researchers therefore analyzed the genome of a specific cell type that is suitable for this study: the cells that line the tiny folds of the inner wall of the intestine, so-called “gut crypts”. All cells in the same crypt—laser microcuttable—derive from the same ancestral stem cell and linearly accumulate mutations with age. Furthermore, in these cells, most mutations are caused by endogenous natural processes—common to other tissues—rather than exposure to environmental toxins. It was then sufficient to divide the number of mutations measured by the age of the individual studied to obtain the mutation rates of each species over the years.

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