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Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research
Sarah M Merrill1,2, Chaini Konwar2,3,4, Fizza Fatima2,3,4
1Department of Psychology, University of Massachusetts Lowell, Lowell, MA, USA.
Insights
Buccal cell proportion in cheek swabs decreases with age in children, impacting DNA methylation studies. Adjusting for this change is crucial for accurate epigenetic age and biomarker research in pediatrics.
Area of Science:
- Epigenetics
- Developmental Biology
- Genomics
Background:
- Cheek swabs are common in pediatric DNA methylation studies.
- The age-related decline in buccal cells in adults is known, but unexamined in children.
- Understanding oral cell composition changes is vital for accurate epigenetic research.
Purpose of the Study:
- To investigate the age-related changes in buccal cell proportion in children.
- To assess the impact of buccal proportion on epigenetic age estimation and its associations.
- To determine the necessity of correcting for buccal proportion in pediatric epigenetic studies.
Main Methods:
- Analysis of cheek swab samples from 4626 children aged 2 months to 20 years.
- Estimation of buccal and neutrophil proportions within samples.
- Correlation analysis between cell proportions, chronological age, and epigenetic age (PedBE).
Main Results:
- Buccal proportion decreased with chronological and epigenetic age in children, but not in adolescence.
- Neutrophil proportion showed an inverse relationship with age.
- Correcting for buccal proportion diminished the association between epigenetic age acceleration and certain health outcomes, while strengthening others.
Conclusions:
- Age-related changes in oral cell composition are significant in children.
- Accounting for buccal proportion is essential for precise pediatric DNA methylation and epigenetic age studies.
- This adjustment refines the interpretation of epigenetic age acceleration in relation to health and development.
Abstract:
Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in children's oral cells is a crucial consideration for cell type-sensitive research.
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