Study Reveals Genetic Risks in Aging Men’s Sperm

In a major study published in the journal Nature, a team of scientists from the Wellcome Sanger Institute and the TwinsUK study at King’s College London mapped the accumulation of harmful mutations in the entire genome of men’s sperm as they age. These findings reveal new ways to study how environmental factors and lifestyle affect the genetic health of future generations.

Importance of the Study and Methodology

In tissues that constantly regenerate, mutations can give some cells an advantage, allowing them to multiply faster than others. This leads to the expansion of identical cell groups, or “clones,” giving them an edge over their neighbors. While most mutations in ordinary body cells are not passed on to offspring, mutations in sperm and egg cells can be inherited.

For the study, the team used high-precision DNA sequencing technology, NanoSeq, to analyze sperm from 81 men aged 24 to 75 from the TwinsUK cohort. This allowed researchers to understand how harmful mutations accumulate with age.

Key Findings

The data showed that about 2% of sperm in men in their early thirties carry disease-causing mutations, increasing to 3-5% in men aged 43 to 74. Among participants in their seventies, 4.5% of sperm contained harmful mutations, indicating a clear link between age and genetic risks to offspring.

The reason for this increase was not merely random DNA errors accumulating over time. Instead, a hidden form of natural selection within the testes seems to give some mutations a reproductive advantage, allowing them to become more prevalent during sperm formation.

Mutations and Their Impact on Genetic Health

Researchers identified 40 genes that appear to benefit from this process, many of which are linked to serious neurodevelopmental disorders in children and inherited cancer risks. While 13 of these genes were previously known to be involved, the new study shows that the phenomenon affects many more genes related to cell growth and development than scientists previously realized.

Although the number of sperm carrying harmful mutations increases with age, not all of these mutations lead to conception or a healthy pregnancy. Some may prevent fertilization or normal embryo development, while others can cause miscarriage.

Future Research Prospects

By uncovering how mutations arise and are shaped by natural selection within sperm, researchers hope to improve reproductive risk assessments and gain a better understanding of how genes, lifestyle, and the environment interact across generations.

In a complementary study also published in Nature, scientists from Harvard Medical School and the Sanger Institute investigated the same phenomenon from a different angle by looking at mutations already passed on to children, rather than those measured directly in sperm.

Conclusion

This study highlights the hidden genetic risks that increase with a father’s age. Some DNA changes 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 harmful mutations to their children. By collaborating with large populations like TwinsUK, scientists can explore how mutations accumulate and evolve with age in healthy individuals, enhancing our understanding of human evolution and heredity.