“Research findings suggest that advanced paternal age is associated with an increased risk of autism spectrum disorder (ASD) in children.”
While maternal health has traditionally been central to research on pregnancy and child development, there is growing recognition that paternal factors also play a role, particularly the father’s age. Several studies have found a modest increase in risk of neurodevelopmental conditions, including autism spectrum disorder, among children born to older fathers. However, the biological mechanisms underlying this association are still not fully understood.
One emerging explanation involves epigenetics, chemical modifications that influence how genes are expressed without altering the underlying DNA sequence. Among these is DNA methylation. Earlier studies have suggested that sperm from older men may carry age-related changes in DNA methylation, but few have explored these patterns on a genome-wide scale or focused specifically on regions that are most likely to influence offspring development.
The Study: Exploring Age-Dependent Methylation at Imprint Control Regions in Human Sperm
In a study, titled “Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring,” published in Aging-US and selected as the Editors’ Choice for January, 2026, researchers investigated how DNA methylation patterns in sperm change with age. The study was led by first authors Eugenia Casella and Jana Depovere, with corresponding author Adelheid Soubry from the University of Leuven.
The research focused specifically on imprint control regions (ICRs), genetic segments that regulate gene activity based on whether the genes are inherited from the mother or the father. These regions play a crucial role during early development and have been associated with developmental disorders when improperly regulated.
To conduct the analysis, the team examined sperm samples from 63 healthy, non-smoking men aged 18 to 35 years.
The Results: Age-Dependent Epigenetic Changes in Sperm Detected Near Autism-Associated Genes
The researchers identified over 14,000 DNA sites (known as CpG sites) where methylation levels were significantly correlated with age. Most of these sites had reduced methylation in older individuals. Of particular interest were 747 sites near known imprint control regions, areas essential for regulating gene expression during early development. When cross-referenced with public databases of autism-associated genes, several of these age-sensitive sites overlapped with genes previously linked to autism spectrum disorder, including MAGEL2, DLGAP2, GNAS, KCNQ1, and PLAGL1.
The Breakthrough: Focus on Imprint Control Regions Reveals Epigenetic Role of Paternal Age
By concentrating on regions of the genome that remain active during the earliest stages of embryonic development, this study provides new evidence supporting the idea that paternal age may influence a child’s developmental outcomes through epigenetic changes in sperm, not just through genetic mutations. This is a step forward in understanding how non-genetic information carried by sperm can affect offspring.
The Impact: Findings Expand Understanding of Paternal Contributions to Offspring Health
These findings should not be interpreted as a reason for older men to avoid fatherhood. Rather, the study refines the understanding of the biological mechanisms that may contribute to autism risk and underscores the importance of considering paternal factors in reproductive health discussions. The research may support future studies aimed at developing early diagnostic tools, risk assessments, or potential interventions. However, such applications are still far from clinical use and require further validation.
Future Perspectives and Conclusion
This study adds to a growing body of evidence suggesting that age-related changes in sperm may play a role in the health of future generations. It is important to note that the observed DNA methylation changes were modest and, on their own, are unlikely to determine whether a child develops autism. Further research, particularly studies that follow these epigenetic patterns through conception, pregnancy, and child development, will be essential to assess their practical significance.
Overall, this work contributes to the broader understanding of reproductive planning and paternal health, offering a more complete picture of the factors that may influence child development.
Click here to read the full research paper published in Aging-US.
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