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Elevated Epigenetic Aging Puts Childhood Cancer Survivors at Risk of Obesity, Other Conditions

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NEW YORK – Young pediatric cancer survivors show faster epigenetic aging compared to adult survivors and are at an elevated risk of developing obesity, chronic health conditions, and dying early, a new study has found.

While previous studies had focused on adult childhood cancer survivors and had found increased epigenetic aging, the authors said that this study is among the first to look at epigenetic age acceleration (EAA) in children and adolescent survivors of pediatric cancer.

"Survivors of childhood cancer, who number more than half a million in the US today, are at increased risk for high morbidity from chronic health conditions (CHCs) and for mortality rates which are typically seen among individuals decades older in the general population, suggesting an accelerated aging phenotype," corresponding author Zhaoming Wang, a scientist in the department of computational biology at St. Jude Children’s Research Hospital, and his colleagues wrote in a cross-sectional study published in JAMA Network Open on Friday. "However, there are limited studies applying molecular biomarkers to quantify the acceleration of aging in this population."

The researchers studied DNA methylation levels in blood samples of 2,846 childhood cancer survivors of European ancestry belonging to five chronological age groups. All participants were part of the St Jude Lifetime Cohort (SJLIFE). The data included new DNA methylation data for 708 patients from a recent study and data for 2,138 patients from a previous study.

Participants were divided into five groups based on their chronological ages at the time their blood samples were taken — childhood (0 to 9 years), adolescence (10 to 19 years), younger adults (20 to 34 years), middle-aged adults (35 to 49 years), and older ones who were at least 50 years old. Then, using multiple epigenetic clocks including the Levine and the Horvath clocks, the researchers calculated cross-sectional annual changes in epigenetic aging (EA) and EAA and compared the results across all the age groups.

The findings from Horvath or Levine clocks showed that children, followed by adolescents, had the highest change rate of EA, which the authors said may be reflective of fast growth and puberty. However, the Hannum and GrimAge epigenetic clocks showed the highest change was in the younger adult cohort.

"EA from Horvath is the only epigenetic clock that included samples collected from children and adolescents in the model training, so it might be the most reliable clock for evaluating epigenetic age in this age range," the authors cautioned.

Wang told GenomeWeb that the main clinical importance of the findings is that health practitioners can introduce anti-aging interventions in younger survivors found to have elevated epigenetic aging early on.

The study also found a link between EAA in children and adolescent survivors and risk for early-onset obesity, increased burden of chronic health conditions later in life, and increased chances of death, based on an analysis of the Levine and GrimAge clocks.

"A temporal association between EAA measured in children and adolescents and early-onset obesity suggests that early intervention with respect to EA may prevent or remediate childhood obesity, which may ultimately ameliorate many other adulthood CHCs," the authors wrote.

Wang said that in the future, his team would like to conduct a longitudinal study where they collect blood samples and measure DNA methylation in the same patients at different periods of time.

One limitation of the study is that the findings cannot be extrapolated to survivors of non-European ancestries without further validation, according to the authors.