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Researchers Identify DNA Methylation Signature Linked to Aging, Autism in Children

NEW YORK – A team from the University of British Columbia, the University of California at Los Angeles, and elsewhere has come up with a non-invasive strategy for estimating a child's age based on DNA methylation profiles in mouth swab samples. 

"This tool has the potential to become the standard reference for epigenetic studies broadly relevant to child development across the spectrum from health to disease," co-senior and co-corresponding authors Michael Kobor, a medical genetics researcher affiliated with the UBC BC Children's Hospital Research Institute and Canadian Institute for Advanced Research, and Steve Horvath, a human genetics and biostatistics researcher at UCLA, and their colleagues wrote in a study published online yesterday in Proceedings of the National Academy of Sciences.

Using array-based methylation profiles generated from buccal epithelial cell samples from more than 1,700 individuals between infancy and 20 years of age, the researchers established and validated an age-related methylation signature based on buccal epithelial cells. This epigenetic signature, dubbed the "Pediatric Buccal Epigenetic" (PedBE) clock, typically coincided with a child's chronological age.

The team has already tested the veracity of the signature in other tissue types, such as saliva or blood samples from children or buccal cell samples from adults. Based on prior findings in adults, it also looked for situations in which DNA methylation-based age predictions differed somewhat from chronological age, uncovering a potential shift in children with autism spectrum disorder (ASD).

"The utility of this highly precise pediatric molecular biomarker has yet to be fully explored," the authors wrote, "however, we anticipate deviations between pediatric [DNA methylation-based] age and chronological age to be representative of developmental processes and/or other pediatric diseases, as they are in adults."

Prior research done using a DNA methylation-based age clock developed for adults suggests that individuals whose chronological age does not match their DNA methylation age are more apt to suffer from conditions such as cognitive decline, the team explained, and are typically thought to be at increased risk of mortality and quicker decline or death.

Even so, "current epigenetic clocks are not very accurate in the pediatric age range, perhaps because DNA methylation changes much faster in children," the authors cautioned, noting that a "high degree of variability from chronological age has been observed."

In an effort to come up with a DNA methylation clock that is accurate across childhood, the investigators began by doing DNA methylation profiling on buccal epithelial cell samples from 1,032 typically developing children under 20 years of age using Illumina Infinium arrays, focusing on 94 CpG cytosine methylation sites in buccal epithelial cells that were subsequently validated in samples from another 689 individuals under the age of 20.

The team's results suggested chronological age was significantly associated with weighted methylation information at the 94 methylation sites. The PedBE methylation signature appeared to roughly correspond with age when used on blood or saliva samples from children, albeit with lower accuracy and larger error rates. And in adult buccal cell samples, its performance was more or less on par with that of an existing clock used across multiple tissue types.

In an independent group of 339 infants sampled over time, the PedBE clock showed potential for picking up differences in gestational age at the three-month point, the researchers reported. Based on PedBE analyses of samples from 47 children with ASD, meanwhile, they saw signs that children with the condition had slightly advanced methylation-based age, on average, compared to 34 typically developing children — results they further validated using data for a few dozen more children with or without ASD.

"The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease," the authors wrote.

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