The longer the lifespan of a species, the slower the accumulation of genetic mutations in its DNA. The confirmation of this biological paradox, hypothesized but never demonstrated, comes from a robust British study published in Nature that adds new pieces to our understanding of aging.
Researchers from Wellcome Sanger Institute and the Zoological Society of London compared the accumulation rate of mutations in various mammals, including humans, and found that, despite the great variability in lifespan and body size, animals end their existence with a similar number of genetic changes.
The puzzle of aging
For over seventy years, in fact, the scientific community has been questioning the role of somatic mutations, which affect the cells of the body, in the aging process. Their appearance is a natural process, which occurs during the entire life of an organism: it is estimated that human cells accumulate between 20 and 50 each year.
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Although the majority of these mutations are harmless, some can compromise the functioning of the cell – and thus at least partially explain the aging process – or initiate a tumor evolution. “In other words, the longer the life of an organism, the higher the number of mutations it would be reasonable to expect, including harmful ones” summarizes Maurizio Genuardiprofessor of medical genetics at the Catholic University in Rome and president of the European Society of Human Genetics.
Another puzzle still unanswered is summed up by the paradox formulated by the statistician Richard Peto. “Since tumors develop from single cells, larger species – and therefore made up of multiple cells – should logically have a much higher risk of cancer. In fact, it has been shown that it is not size dependent. body: the elephant has a much lower incidence of tumors than that of smaller animals “continues the expert.
The currently highest-rated explanation argues that larger animals have developed more effective strategies for preventing cancer. However, any of these mechanisms have never been shown to reduce the accumulation of genetic changes.
I study
Researchers at the Wellcome Sanger Institute measured the somatic mutation rates in single stem cells of 16 mammalian species, covering a broad spectrum of longevity and body mass: from humans to mice, through the lion, the giraffe, the tiger, the hairless mole and others. Genome-wide sequences were derived from 208 intestinal crypts taken from 48 individuals.
Genetic signatures of the mutational processes provided information on the processes taking place, allowing researchers to demonstrate that somatic mutations accumulated linearly over time and that they were caused by similar mechanisms in all considered species, including humans.
The genetic changes identified in the study suggest that the diseases of old age are similar in a wide range of mammals, regardless of whether it begins at seven months or at 70.
Evidence of a possible role played by somatic mutations in aging emerged from the finding that the mutation rate decreased as the lifespan of each species increased. On average, a giraffe is 40,000 times larger than a mouse and a human being lives 30 times longer, but the difference in the number of mutations per cell between the three species, given their respective longevity, was limited.
The conclusions
According to Alex Caganfirst author of the study, “Finding that lifespan is inversely proportional to the rate of somatic mutations suggests that they may play a role in aging. In the future, it would be fascinating to extend these studies to even more diverse species, such as insects or plants”.
Despite this, the Peto paradox remains unexplained: after considering the lifespan, the authors unsuccessfully sought an association between the somatic mutation rate and the body mass of the animals. “Although the hypothesis of regulation of the mutation rate is an elegant solution to explain the incidence of tumors among different species, evolution does not seem to have taken this path. It is entirely plausible that, every time a species evolves larger than its ancestors, biology devises a different solution to this problem, “adds the colleague Adrian Baez Ortega.
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Aging in humans
Despite the result, it is the British researchers themselves who underline how far we are still from understanding aging, both in animals and in humans. “The progressive accumulation of somatic mutations over the course of life is one of the processes believed to underlie aging: the more times a cell replicates, the greater the number of mutations that emerge.
The changes in DNA can alter the functionality of proteins which in turn can induce physiological changes in the organism “resumes Genuardi, recalling however, that there are still few studies that associate the accumulation of somatic mutations with biological age in humans. .
“However, we know that aging depends on a set of factors. Among these are the epigenetic alterations, which can change the functioning of the DNA and therefore the activity of the genes, and the shortening of the telomeres of the chromosomes: these small portions of DNA, which protect the ends of the chromosomes, is reduced with each replication “concludes the expert.