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Differences in the rate that genetic mutations accumulate in healthy young adults could help to predict remaining lifespan in both sexes and the remaining years of fertility in women,¹ according to a study from the University of Utah.

Published in Scientific Reports, the research found that young adults who acquired fewer mutations over time lived about five years longer than those who acquired them more rapidly. This is a difference comparable to the effects of smoking or lack of physical activity.

Women with the highest mutation rates had significantly fewer live births than other women and were more likely to be younger when they gave birth to their last child. According to the authors, this suggested that the high rate of mutation was affecting their fertility.

Researchers had sequenced DNA from 61 men and 61 women who were grandparents in 41 three-generational families. They then analysed blood DNA sequences in trios consisting of pairs of grandparents from the first generation and one of their children from the second generation. This is because germline mutations (variations in germ cells) are passed on to offspring. Mutations found in the child's blood DNA that were not present in either parent's blood DNA were then inferred to have originated in the parents' germlines. The researchers were then able to determine which parent each germline mutation came from and, therefore, the number of such mutations each parent had accumulated in egg or sperm by the time of conception of the child.

Knowing this enabled the researchers to compare each first-generation parent to others of the same sex and estimate their rate of ageing.

Richard Cawthon, a research associate professor of human genetics at the University of Utah, said: "So, compared to a 32-year-old man with 75 mutations, we would expect a 40-year-old with the same number of mutations to be ageing more slowly.

"We'd expect him to die at an older age than the age at which the 32-year-old dies."

The scientists found that mutations began to occur at an accelerating rate during or soon after puberty, suggesting that ageing begins in our teens.

Cawthon added: “The ability to determine when ageing starts, how long women can stay fertile, and how long people can live is an exciting possibility.

"If we can get to a point where we better understand what sort of developmental biology affecting mutation rates is happening during puberty, then we should be able to develop medical interventions to restore DNA repair and other homeostatic mechanisms back to what they were before puberty.

“If we could do that, it is possible people could live and stay healthy much longer.”

References

1. https://www.nature.com/articles/s41598-020-66867-0