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Accumulating fewer genetic mutations linked to living a longer life

Genetic mutations passed down through generations may hint at how long a person will live

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The number of genetic mutations a person amasses in their reproductive cells could help tell us how long they will live – and having a lower proportion of these germ line mutations may also influence when a woman’s fertility starts to decline.

Richard Cawthon at the University of Utah and his colleagues analysed previously collected genetic information from 61 men and 61 women, all of whom were grandparents and most of whom had died by 2018, with the exception of two. These people were part of a project to build a genetic database of families across three generations.

Because mutations in reproductive cells can be passed to the next generation, the researchers were able to calculate how many the grandparents had before they had children, and they did the same for the second and third generations. In an analysis of 41 families in the database, the team found that a slower accumulation of mutations was linked to longer life.

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People with mutation numbers in the top 75 per cent were more than twice as likely to die from any cause over the study period than those in the bottom 25 per cent, who had an average survival advantage of almost five years. Men accumulated more of these mutations than women, though it isn’t yet known whether this affects their lifespan.

This lends support to the idea that ageing is down to the accumulation of mutations, driving cell damage and death.

The team also found that women who harboured fewer mutations were older at the time of their last birth and had more children who weren’t stillborn on average than those with more mutations.

“Inferring mortality risk from the de novo germ line is certainly unexpected and exciting,” says Scott Kennedy at the University of Washington in Seattle. “The fairly clear association between mutation rate and mortality is a potentially very important and novel finding” though the interpretations around women’s fertility are more tentative, he says.

The researchers note that the genetic database includes families selected for large numbers of siblings and living grandparents, which could lead to somewhat higher-than-average fertility rates and lifespans.

“Once we have good, strong associations of biomarkers with how long people live, the idea is that we might be able to figure out what the mechanisms of ageing are and come up with medical and lifestyle interventions that can help people stay healthy as long as possible,” says Cawthon.

Journal reference: Scientific Reports, DOI: 10.1038/s41598-020-66867-0

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