image: Figure 1. Workflow to assess age-related DNA methylation changes in sperm and biomarker selection for ASD. Data generated from the Illumina HumanMethylation450 BeadChip went through the following analytic procedures. (1) global DNA methylation (mean per subject) by age. (2) DNA methylation at individual CpGs by age. Note, additional tests were performed, as described in the methods section. (3) We subdivided our outcome data as follows: Unmethylated (UM, mean β-value <0.2), Hemi-methylated (HM, 0.20≤ mean β-value ≤0.80), and Fully methylated (FM, mean β-value >0.80), defined by the mean DNA methylation per CpG site (of all subjects). The top 30 of the most significant results (lowest adjusted p-value) were classified by: (4) significance (top 90), direction (positive, negative), and magnitude (absolute Delta-M >0.1). All age-related DMCs (n = 14,622) were analyzed in terms of the following approaches: (5) chromosome location, island content, functional genomic allocation, and (6) gene ontology (GO). We compared our results with: (7) similar published reports, and (8) listed data on imprinting. Finally, (9) a focus was applied on all DMCs using Simons Foundation Autism Reference Initiative database and other publicly available databases on ASD. (10) We selected a set of potential biomarkers for ASD within our set of imprinted genes.
Credit: Copyright: © 2025 Casella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Research findings suggest that advanced paternal age is associated with an increased risk of autism spectrum disorder (ASD) in children.”
BUFFALO, NY — January 16, 2026 — A new research paper was published in Volume 17, Issue 12 of Aging-US on December 29, 2025, titled “Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring.”
The study – selected as our Editors’ Choice for January, 2026 – was led by first authors Eugenia Casella and Jana Depovere, with corresponding author Adelheid Soubry from the University of Leuven. The research shows that a man’s age is linked to specific changes in sperm DNA that may influence early development in children. These findings are relevant as autism diagnoses have increased while many men are becoming fathers later in life.
Autism spectrum disorder is a growing public health concern affecting millions of families worldwide. The study focused on DNA methylation, a natural process that helps regulate how genes function without changing the DNA sequence itself. DNA methylation plays a key role during early development and can be sensitive to age-related biological changes.
Researchers analyzed sperm samples from 63 healthy, non-smoking men between the ages of 18 and 35. DNA methylation was measured at hundreds of thousands of locations across the genome. The analysis identified more than 14,000 DNA sites where methylation levels changed with age, with most showing a gradual decrease as men got older.
“To identify sperm-specific marks, we conducted an epigenome-wide association study in sperm from 63 men, using the Illumina 450K array.”
While individual changes were small, their location within the genome was important. Many age-related changes occurred near imprint control regions, which help ensure that certain genes are active only from one parent. These regions are established during sperm development and are usually maintained after fertilization. Disruptions in these regions may affect how genes are regulated in offspring.
Researchers found that several genes affected by age-related DNA changes have previously been linked to autism. These genes are involved in brain development, nerve communication, and early growth. Changes in their regulation may increase vulnerability to neurodevelopmental differences.
Overall, the findings provide new biological insight into earlier evidence linking paternal age to child health. However, the authors note that autism is a complex condition shaped by many genetic and non-genetic factors, and no single cause has been identified. The study results suggest that age-related changes in sperm DNA may be one contributing factor. By clarifying how paternal age influences sperm biology, this research supports future studies in reproductive health as family planning increasingly shifts toward later parenthood.
Paper DOI: https://doi.org/10.18632/aging.206348
Corresponding author: Adelheid Soubry – adelheid.soubry@kuleuven.be
Abstract video: https://www.youtube.com/watch?v=XC3p49Uw49w
Keywords: aging, epigenome, sperm, 450K, imprinting, autism
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Journal
Aging-US
Method of Research
News article
Subject of Research
People
Article Title
Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring
Article Publication Date
29-Dec-2025
COI Statement
We declare no competing interests. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.