Study shows older fathers transmit more disease mutations through selfish sperm
A new study reveals that older men pass on significantly more disease-causing genetic mutations to their children due to the rapid proliferation of mutant sperm stem cells. Researchers found that the proportion of mutated sperm rises sharply with age, from 1 in 50 for men in their early thirties to nearly 1 in 20 by age 70. This phenomenon, driven by 'selfish' mutations, heightens risks for severe disorders in offspring.
The research, published in Nature, sequenced over 100,000 sperm samples from 81 men of varying ages, alongside their blood cells, using a novel technique that sequences both strands of the DNA double helix to minimize errors. This allowed identification of mutations in more than 40 genes that cause sperm stem cells to proliferate selfishly, outcompeting normal cells and exponentially increasing the share of mutated sperm over time.
"The size of the effect across the genome was much higher than any of us thought," said Matthew Neville from the Wellcome Sanger Institute, a team member. These selfish mutations, though rare overall, target key genes and lead to severe outcomes. "For the most part, they're fairly severe neurodevelopmental disorders," Neville explained, noting links to autism in at least two genes and elevated cancer risks in others.
The findings build on Anne Goriely's 2003 insight at the University of Oxford that certain mutations make sperm stem cells selfish, explaining higher-than-expected rates of conditions like achondroplasia. Each person carries about 70 new mutations, with 80% originating in fathers' testes, but selfish mutations amplify this paternal contribution nonlinearly with age.
"The paper clearly shows that older fathers have a higher risk of passing on more pathogenic mutations," commented Raheleh Rahbari, also at the Sanger Institute. Ruben Arslan from the University of Witten in Germany praised the study, adding that additional paternal age is less harmful when younger than when older.
Goriely emphasized shifting focus: "We have known for a long time that being an older parent is not a good idea. The emphasis used to be really associated with the mother. Now we understand that both parents contribute to the health of their children."
Unlike blood cells, where mutations rose with smoking, heavy drinking, or obesity, sperm mutations accumulated eight times slower and showed no such environmental links, suggesting protective mechanisms in testes. Families might consider sperm freezing for younger men or screening for older ones, though decisions remain personal, per Neville: "It’s for families to consider when they’re making their own decisions."