New research has found that harmful genetic changes in a man's sperm become much more common as he gets older. This happens partly because some of these harmful changes are actually favored (or given an advantage) during the process of making sperm. A major study, published in the journal Nature, mapped out exactly how these damaging DNA changes increase across the genome as men age. The findings were made by researchers from the Wellcome Sanger Institute and King's College London, using the TwinsUK study. How Harmful Changes Increase With Age As cells in the body divide, changes in their DNA (called mutations) occur. Sometimes, a mutation gives a cell a "competitive advantage," allowing it to multiply faster than other cells. In the testes, where sperm is made, this process can favor cells that carry harmful mutations. When these mutated cells multiply, they create a large group (a "clone") of sperm-producing cells that carry the same genetic flaw. Unlike regular cells, mutations in sperm cells can be passed down to children. How Can You Identify Problems With DNA? Researchers used a very accurate DNA sequencing method (called NanoSeq) to look at sperm from 81 healthy men, aged 24 to 75. In men in their early 30s, about 2% of their sperm carried disease-causing mutations.In middle-aged and older men (43 to 74 years old), this rate jumped to 3% to 5%.This shows a clear link: the older a father is, the higher the genetic risk for his children. This risk is not just from random changes, but from a subtle form of natural selection that gives certain mutations an advantage during sperm production. What Genes Were Linked to Disease The researchers found 40 genes where specific DNA changes are favored during sperm production. Many of these genes are linked to: Serious neurodevelopmental disorders in children.Inherited cancer risk.Other childhood diseases.This process, where harmful mutations are given a competitive edge, is much more widespread than scientists previously thought. How Does The Sperm Quality Affect Children? In a related study, researchers looked at DNA from over 54,000 groups of parents and children to see which mutations were actually passed on. This separate research confirmed the initial findings: certain mutations that are linked to disorders and cancer gave sperm cells a competitive edge. The study showed that these mutations can increase the rate of new mutations in sperm by about 500 times. This helps explain why some rare genetic disorders appear even when the parents don't have the mutation in their own body DNA. Can Lifestyle Changes Lower This Risk? Researchers were surprised by how much this selection process in the testes increases the number of sperm carrying mutations linked to serious diseases. As Dr. Matthew Neville, a lead author, said, “We found a hidden genetic risk that increases with paternal age.” The hope is that understanding this process will help doctors better assess reproductive risks and explore how external factors like lifestyle and environment might affect the genetic risks passed down to the next generation.
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