Scientists have discovered that as men age, their sperm accumulate “selfish” mutations — genetic flaws that allow faulty sperm to thrive and multiply inside their testes, even though they increase the risk of their children inheriting diseases.
Scientists from the the Wellcome Sanger Institute and King’s College London charted how harmful changes in DNA, or mutations, accumulate in sperm as men grow older.
They found that as men age, so-called “selfish” mutations come to be favoured during the process of sperm production. This increases the chances that genetically defective sperm cells can outcompete healthy ones.
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Describing the mutations as “selfish” does not mean that conscious or deliberate decisions are made. Instead, it refers to genetic changes that help a sperm-producing cell make more copies of itself inside the testes, even if those same changes are harmful when passed to a child.
These mutations give the sperm a reproductive advantage within the man’s body. In other words, they “win” locally — but at a potential cost to the next generation.
The research, published in Nature, offers a new picture of how paternal age may influence the genetic health of children. Although the study does not make clinical recommendations, the findings could inform decisions on whether men who plan to have offspring later in life should have sperm frozen and banked when they are young.
Using an ultra-precise genetic sequencing method known as NanoSeq, the team analysed sperm from 81 healthy men aged 24 to 75. They discovered that about 2 per cent of sperm from men in their early thirties carried disease-causing mutations, compared with 4.5 per cent in men aged 70.
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Not every sperm with a mutation will fertilise an egg, and many affected embryos may not survive. But the gradual rise in faulty sperm could help explain why certain rare diseases occur more frequently than others.
The researchers identified 40 genes where harmful mutations appear to be favoured during sperm production. Many of the mutations are involved in cell growth and development and involve changes to genes known to cause developmental disorders and inherited cancers when passed on.
Matt Hurles, director of the Wellcome Sanger Institute, said: “Our findings reveal a hidden genetic risk that increases with paternal age. Some changes in DNA not only survive but thrive within the testes, meaning that fathers who conceive later in life may unknowingly have a higher risk of passing on a harmful mutation to their children.”
The sperm and blood samples used in the research came from men enrolled in TwinsUK, the UK’s largest adult twin registry. The cohort includes thousands of identical (monozygotic) and fraternal (dizygotic) twins who have been followed over decades, providing detailed health, lifestyle and genetic records.
This allowed the team to compare changes both between individuals of the same age and within the same men as they aged.
Raheleh Rahbari, of the Wellcome Sanger Institute, senior author of the study, said: “There’s a common assumption that because the germline [the reproductive cells that give rise to sperm and eggs, and whose DNA is passed on to children] has a low mutation rate, it is well protected. But in reality, the male germline is a dynamic environment where natural selection can favour harmful mutations, sometimes with consequences for the next generation.”