News | Science shows that older paternal age increases the risk of genetic mutations in children
Scientists have extensively studied the relationship between parental age and children's health. Previous research focused mainly on the effects of advanced maternal age, such as congenital abnormalities and pregnancy complications. A recent study in Fertility and Sterility suggests that increasing paternal age may also affect genetic stability in children and raise the risk of certain conditions.
Advanced paternal age and genetic mutations
The study found that the number of de novo mutations (DNMs) in children increases with paternal age. These mutations are associated with various genetic disorders. Using whole-exome sequencing (WES) and whole-genome sequencing (WGS) to analyze data from multiple families, researchers found that 80% of de novo mutations originated from the father and increased linearly with paternal age.
Male germ cells, or spermatogonial stem cells, continually divide and replicate throughout life, and DNA replication errors can occur with each division. These small mutations generally cause no immediate symptoms in the father, but accumulated mutations may cause genetic disorders in the next generation.
How do genetic mutations affect children's health?
Some conditions linked to de novo mutations, including autism, schizophrenia, Down syndrome and Marfan syndrome, were significantly associated with advanced paternal age. Risks of pregnancy complications such as preterm birth, low birth weight and fetal distress may also rise with paternal age.
Further analysis found that most mutations had specific “mutational signatures,” similar to spontaneous mutations in tumor cells. This suggests that increasing paternal age may promote accumulation of certain mutations and affect children's health.
“Selfish selection”—a mechanism for mutations in sperm from older men
In addition to DNA replication errors, the study described **“selfish selection”**, which may accelerate mutation accumulation in sperm as men age.
In this process, some mutations in spermatogonial stem cells (SSCs) give the cells a competitive advantage and allow faster proliferation. As these mutant cells expand with age, the proportion of sperm carrying the mutations rises substantially. The mutations may not affect the father's health but can increase a child's risk of certain Mendelian disorders, including achondroplasia and Noonan syndrome.
The process resembles clonal expansion in tumor cells but occurs in germ cells and therefore affects genetic stability in the next generation.
Long-term effects of paternal age on the next generation
At the individual level, the effect of advanced paternal age on children's health remains small. From a population-health perspective, however, the trend toward later fatherhood worldwide may allow the cumulative effects of genetic mutations to influence future generations.
The team called for greater attention to paternal age in family planning and for more information in medical counseling and reproductive decisions. Further research is needed to assess long-term effects and develop appropriate public-health responses.
News | Science shows that older paternal age increases the risk of genetic mutations in children
News | Science shows that older paternal age increases the risk of genetic mutations in children
Scientists have extensively studied the relationship between parental age and children's health. Previous research focused mainly on the effects of advanced maternal age, such as congenital abnormalities and pregnancy complications. A recent study in Fertility and Sterility suggests that increasing paternal age may also affect genetic stability in children and raise the risk of certain conditions.
Advanced paternal age and genetic mutations
The study found that the number of de novo mutations (DNMs) in children increases with paternal age. These mutations are associated with various genetic disorders. Using whole-exome sequencing (WES) and whole-genome sequencing (WGS) to analyze data from multiple families, researchers found that 80% of de novo mutations originated from the father and increased linearly with paternal age.
Male germ cells, or spermatogonial stem cells, continually divide and replicate throughout life, and DNA replication errors can occur with each division. These small mutations generally cause no immediate symptoms in the father, but accumulated mutations may cause genetic disorders in the next generation.
How do genetic mutations affect children's health?
Some conditions linked to de novo mutations, including autism, schizophrenia, Down syndrome and Marfan syndrome, were significantly associated with advanced paternal age. Risks of pregnancy complications such as preterm birth, low birth weight and fetal distress may also rise with paternal age.
Further analysis found that most mutations had specific “mutational signatures,” similar to spontaneous mutations in tumor cells. This suggests that increasing paternal age may promote accumulation of certain mutations and affect children's health.
“Selfish selection”—a mechanism for mutations in sperm from older men
In addition to DNA replication errors, the study described **“selfish selection”**, which may accelerate mutation accumulation in sperm as men age.
In this process, some mutations in spermatogonial stem cells (SSCs) give the cells a competitive advantage and allow faster proliferation. As these mutant cells expand with age, the proportion of sperm carrying the mutations rises substantially. The mutations may not affect the father's health but can increase a child's risk of certain Mendelian disorders, including achondroplasia and Noonan syndrome.
The process resembles clonal expansion in tumor cells but occurs in germ cells and therefore affects genetic stability in the next generation.
Long-term effects of paternal age on the next generation
At the individual level, the effect of advanced paternal age on children's health remains small. From a population-health perspective, however, the trend toward later fatherhood worldwide may allow the cumulative effects of genetic mutations to influence future generations.
The team called for greater attention to paternal age in family planning and for more information in medical counseling and reproductive decisions. Further research is needed to assess long-term effects and develop appropriate public-health responses.
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