The older we live, the slower we mutate

This is a new step in the long hunt for the causes of biological aging. New, but not so new: the study published on April 13 in the journal Naturein reality, comes to validate “a hypothesis put forward in 1952 by a future Nobel Prize winner, Peter Medawar [1915-1987]but so far impossible to demonstrate: 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 induce a critical state for the functioning of these cells. »

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The immense development of sequencing capabilities has changed the game. Thanks to which British researchers were able to prove the reality of this phenomenon. Coordinated by the Wellcome Sanger Institute (UK), they counted DNA damage in cells of sixteen mammalian species, covering a wide range of lifespans and body sizes: cat, dog, horse, cow , rabbit, ferret, mouse, rat, naked mole-rat, giraffe, porpoise, lion, tiger, ring-tailed lemur, black and white colobus and human species. For five of them, several individuals (56 in total) of different ages were analyzed.

As a result, longer-lived species acquire DNA mutations in their somatic (non-sex) cells more slowly than shorter-lived species. This observation partly explains the famous “Peto paradox”, named after the British epidemiologist Richard Peto who stated it in 1977. A whale or an elephant, for example, have many more cells and live much longer than ‘a mouse. The probability that one of their cells undergoes mutations – leading to its uncontrolled proliferation – is therefore higher. Logically, these behemoths should have an increased risk of cancer. However, it is not the case.

Very marked differences

But how can we estimate the rate at which these mutations accumulate in the cells of each species? Difficult to follow an individual all his life! The researchers therefore analyzed the genome of a particular type of cell, suitable for this examination: the cells that line the tiny folds of the inner wall of the colon, or “intestinal crypts”. All the cells of the same crypt – micro-cuttable by laser – derive from the same ancestral stem cell and accumulate mutations in a linear fashion with age. In these cells, moreover, most mutations are caused by endogenous natural processes – common to other tissues – rather than by exposure to environmental toxins. It was then enough 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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