Men can have children much later than women, but doing so raises the risk that their children will develop hereditary diseases. A study found that as men age, harmful mutations increase in sperm DNA, and some of those mutations are naturally selected because they help sperm production.
Researchers at the Wellcome Sanger Institute in the United Kingdom published the paper with these findings on the 8th (local time) in the journal Nature. Natural selection is the core principle of evolution in which individuals with traits well adapted to the environment survive and reproduce more successfully, passing those traits on to the next generation.
According to the paper, about 2% of sperm from men in their early 30s carried disease-causing mutations, but that rose to 3%–5% in sperm from middle-aged (43–58) and older (59–74) men. For a 70-year-old man, it rose to 4.5%. The researchers said an average of 1.7 new mutations arise each year in a single sperm cell. This means the genetic risk to offspring increases as the father gets older.
Mutations in somatic cells, which make up bones or organs, affect only the individual, but mutations in germ cells such as sperm or eggs are passed to the next generation. However, because DNA genetic information could not be decoded with sufficient accuracy, it had been difficult to measure how favored such mutations are in sperm.
The research team extracted DNA from the sperm of 81 healthy men aged 24 to 75 and decoded it using NanoSeq, an ultra-precise sequencing method. DNA, the blueprint of life, has its genetic information determined by the order in which four bases are linked. Proteins are synthesized according to the order in which the bases are linked, governing life processes. Decoding genes is the process of identifying these base sequences.
The researchers said NanoSeq is so accurate—fewer than five decoding errors per 1 billion DNA bases—that they could identify variants in sperm almost perfectly. They also analyzed blood samples alongside sperm to confirm that variants found in sperm were pure germline variants not present in somatic cells such as skin and bone.
What was interesting was that mutations did not accumulate randomly in sperm with age; some mutations were selected. Germ cells with certain mutations tend to survive better or proliferate faster than other cells, producing more sperm.
The researchers identified 40 variants advantageous for natural selection. Previously, only 13 were known. These included genes associated with childhood diseases, severe neurodevelopmental disorders, and hereditary cancer risk. The academic community said the findings open up possibilities to explore how environmental factors such as lifestyle changes may affect the genetic risks passed on to future generations.
A joint team from Harvard Medical School and the Sanger Institute published, on the same day in Nature, results from analyzing not the sperm itself but DNA already transmitted to children. They compared DNA from 54,000 parent–child pairs and genomic data from 800,000 adults.
The analysis identified about 30 genes that increase particularly when mutations arise in sperm. Many of these overlapped with the 40 genes identified when analyzing sperm itself in the first study.
Although the proportion of sperm carrying harmful mutations increases with age, that does not necessarily mean children with bad mutant genes are more likely to be born to older fathers. The researchers said, "Some mutations can cause problems with fertilization or embryo development, or lead to pregnancy loss," adding, "More research is needed to understand precisely how increases in sperm mutations translate into health outcomes for children."
References
Nature(2025), DOI: https://doi.org/10.1038/s41586-025-09448-3
Nature(2025), DOI: https://doi.org/10.1038/s41586-025-09584-w