Children born to older mothers have changes in their DNA methylation, according to an analysis by NICHD researchers. The changes involve the presence or absence of tags on DNA called methyl groups, which switch genes on or off without changing their structure. The findings, which need to be confirmed by future studies, may provide a potential explanation for the slightly higher risk of certain health conditions observed in children born to older parents.
Principal investigator Edwina Yeung, Ph.D., of NICHD’s Epidemiology Branch, conducted the study with a team of international investigators. It appears in Aging Cell.
Background
The age at which people have children has risen in recent years. For example, in the United States, the median maternal age at delivery rose from 27 years in 1990 to 30 years in 2019. Other studies have linked older parental age with adverse outcomes in children related to cognitive development, cardiovascular development, allergies, and cancer.
A potential explanation for these associations is that methylation changes occur in DNA as people age, and these changes are passed on to their offspring. Previous studies have shown that aging-related methylation changes occur in egg and sperm cells. Similarly, aging in eggs has been associated with DNA methylation changes in the embryo and the placenta.
Results
Previous studies on the potential association of parental age with offspring DNA methylation are inconclusive. For the current study, researchers analyzed data from an international study of the methylation patterns of more than 9,500 newborns and 2000 children ages 5 to 10 years old.
In newborns, the investigators identified 33 sites near 13 genes where DNA methylation patterns were associated with maternal age. Of these, eight were located either in or near the MTNR1B gene, which codes for a melatonin receptor. Although these associations were weaker in blood samples from 5- to 10-year-olds, they still persisted.
The investigators also found higher DNA methylation at three sites near the RTEL1-TNFRSF6B gene in newborns, which were also associated with maternal age. Again, the associations were still present but weaker in 5- to 10-year-olds.
Associations with DNA methylation changes and paternal age did not reach statistical significance in the study.
Significance
Mutations in MTNR1B are associated with health effects, such as type 2 diabetes and sleep and neuropsychiatric disorders, conditions that occur more frequently among children of older mothers. The RTEL1-TNFRSF6B gene is associated with biochemical pathways controlling inflammation and allergies. Methylation changes near these genes could help explain the association between older parental age and childhood allergic rhinitis and food allergies.
Next Steps
The authors noted that their results provide support for the concept that changes in DNA methylation associated with older maternal age could play a role in children’s health. However, additional studies are needed.
Reference
Yeung, E, et al. Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium. Aging Cell. 2024. DOI: 10.1111/acel.14194
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