Overview

• Paired Nature papers detail direct NanoSeq profiling of sperm from 81 men aged 24 to 75 and a complementary analysis of more than 54,000 parent–child trios and 800,000 individuals.
• The share of sperm carrying disease-causing mutations rose from about 2% in men in their early 30s to 3–5% in men aged 43–74, reaching roughly 4.5% in some 70-year-olds.
• The rise is attributed not only to accumulated errors but to selection within the testes that favors certain mutations, leading to clonal expansion of affected spermatogonial cells.
• Researchers identified around 40 genes enriched by this process in sperm, with more than 30 overlapping in the trio study, many linked to neurodevelopmental disorders and inherited cancer risk.
• The trio-based analysis estimated that some hotspots experience roughly 500-fold higher local mutation rates, while authors caution that many mutated sperm will not result in a live birth and that outcome-focused research is needed.