ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples

Authors: Fang Fang, et al.

Who sponsored this study?

The Environmental influences on Child Health Outcomes (ECHO) Program, Office of The Director, National Institutes of Health supported this research.

Why was the study needed?

A molecular process called DNA methylation, or DNAm, 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, only epigenetic clocks for pediatric populations have only recently been built. Epigenetic clocks also allow scientists to evaluate the impact of various environmental exposures on early-life development and children’s health outcomes.

This study conducted 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. It is important for scientists to understand how these clocks perform in different tissue types and developmental stages throughout early life to ensure researchers are designing studies appropriately and then correctly interpreting the results of these studies.

What were the study results?

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.

Footnote: Results reported here are for a single study. Other or future studies may provide new information or different results. You should not make changes to your health without first consulting your healthcare professional.

What was the study's impact?

This study provides practical recommendations for selecting the most appropriate epigenetic clock in different research contexts, therefore leading to more accurate estimates of biological age. The findings of this study may help scientists make better research tools, improving child health research.

Who was involved?

Researchers used data from 3,789 children, who contributed a total of 4,555 samples, from 20 ECHO research sites. The sample set consisted of 2,273 male and 2,282 female samples.

What happened during the study?

The researchers evaluated seven different epigenetic clocks based on the DNAm data generated from the selected sample set. The study evaluated each clock in corresponding tissues based on previous study results, and then compared clocks 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.

What happens next?

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. Future studies may examine the effects of genetics on the performance of different epigenetic clocks.

Where can I learn more?

Access the full journal article, titled “Evaluation of Pediatric Epigenetic Clocks Across Multiple Tissues,” in Clinical Epigenetics.

The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Published October 9, 2023

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ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples

New ECHO Research Identifies Best Epigenetic Tests to Use for Different Pediatric Tissue Samples

Posted on October 9, 2023October 19, 2023 by Jodi Snare

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.

Read the research summary.

ECHO Researcher Publishes Review on Epigenetic and Environmental Influences on Generational Health

Posted on July 15, 2021December 5, 2023 by Jodi Snare

Previous studies show that the environment may affect the health of multiple generations in one family. Environmental exposures and behaviors can change a person’s epigenetics, the markers and structural changes that direct how genes are read and understood. These markers and changes form a “molecular memory” can be passed down across generations. For example, if a pregnant woman is exposed to a chemical, her children’s and possibly grandchildren’s health may be impacted through epigenetic changes.

Knowing this, ECHO researcher Carrie Breton, ScD of the University of Southern California and her writing team gathered information from past studies to provide a review of existing epigenetic research and evaluate the potential role of epigenetics in the passing on of health risks to later generations. Breton served as lead author and was accompanied by other ECHO researchers, such as Rebecca Fry, PhD of the University of North Carolina at Chapel Hill; Alison Hipwell, PhD of the University of Pittsburgh; Cristiane Duarte, PhD of Columbia University; Linda Kahn, PhD of NYU Langone Health; Rachel Miller, MD of Icahn School of Medicine at Mount Sinai; and Joseph Braun, PhD of Brown University. Their research, titled “Exploring the evidence for epigenetic regulation of environmental influences on child health across generations” is now published in Communications Biology.

“While complex childhood disorders clearly have genetic components, it is increasingly clear that the environment can play a substantial role in affecting risk, even across generations. Our question was how much evidence exists to support epigenetic mechanisms as one route for conveying that risk,” said Breton.

To collect information, the writing team reviewed several studies on humans and animals investigating the role of epigenetics in multigenerational health. They used these studies to build a broad view of how environmental exposures and behaviors can have a lasting impact on the health and well-being of children for generations to come.

Research from this review found evidence in animals and humans that environmental exposures can affect health across multiple generations, potentially through altered epigenetics. One of the challenges of studying epigenetics in humans is untangling the complex interactions between epigenetic, genetic, and environmental factors associated with certain health outcomes. The scale of the ECHO Program makes it uniquely situated to address questions about environmental exposures across generations.

“By looking at many results together, scientists can find important patterns and form a better understanding of how the environment can affect the health of a mother, child, and grandchild,” said Fry.

Read the research summary.

ECHO

Environmental Influences on Child Health Outcomes

epigenetics

ECHO Cohort Study Identifies Best Tests of Biological Age to Use for Different Types of Pediatric Tissue Samples