Collaborative ECHO research led by Fang Fang, PhD, of the Genomics and Translational Research Center of RTI International evaluates multiple epigenetic clocks to test their accuracy when used to predict the biological age of children. This research, titled “Evaluation of Pediatric Epigenetic Clocks Across Multiple Tissues,” is published in Clinical Epigenetics.
DNA methylation, or DNAm, is a molecular process that adds a tag to the DNA that can control gene expression. Certain well-studied DNAm have been associated with many age-related chronic diseases, including aging itself.
Researchers have developed biochemical models called epigenetic clocks that use DNAm to estimate an individual’s biological age. Scientists have studied these clocks in adult populations in whom accelerated biological age (DNAm-predicted age older than actual chronological age) seems strongly connected to age-related health complications. However, epigenetic clocks for pediatric populations have only recently been built. To understand how these clocks perform in different tissue types and developmental stages, researchers used data from 3,789 children from 20 ECHO research sites to conduct a comprehensive evaluation on seven of these epigenetic clocks—Horvath, Knight, Bohlin, Lee, Mayne, PedBE, and NeoAge—all of which researchers developed for different purposes and tissue types.
The study evaluated each clock to their corresponding tissues, and then compared them across different tissue samples. After comparing the suitability of various epigenetic clocks for each tissue type, researchers evaluated their performance across diverse populations. This evaluation included comparing epigenetic clocks between preterm and term infants within the same tissue type, across different self-reported racial groups, between males and females, and across different tissue types within the same set of participants.
The results of this study suggest that the best epigenetic clock to use depends on the type of sample being studied. For example, the Bohlin and Knight clocks were very similar when predicting gestational age from blood cell samples; the Lee clock outperformed the Mayne clock in predicting gestational age from placental samples; and the PedBE clock was more accurate than the Horvath clock at predicting chronological age from buccal cells. However, the Horvath clock was better at predicting chronological age when using blood cells samples.
The study results suggest the importance of researchers choosing the appropriate clock depending on the focus of their study, and provides practical recommendations for selecting the most appropriate epigenetic clock in different research contexts. The findings of this study may help scientists make better research tools, improving child health research.
“It is important for scientists to understand how these clocks perform in different tissue types and developmental stages throughout early life to ensure they are designing studies appropriately and then correctly interpreting the results of these studies,” Dr. Fang said.
Future studies may use the various epigenetic clocks as recommended to check the health of babies and children. However, researchers should interpret this data with caution as it pertains to conclusions about the performance of specific epigenetic clocks in pediatric populations with varied health backgrounds. In addition to practically applying the recommendations provided by this research, future studies may also examine the effects of genetics on the performance of different epigenetic clocks.
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