Age-related differences in metabolome composition in a healthy pediatric population: A pilot analysis

Metabolic profiling of biofluids provides a comprehensive overview of physiological processes occurring at the molecular, cellular, tissue, and organ levels. Accounting for age-related variation in the metabolome is critical to accurately interpret these effects in blood-based metabolomics research. In this study, we sought to characterize the blood metabolome of healthy pediatric patients and assess whether metabolite concentrations differ across age groups and stages of sexual maturation. A total of 44 plasma samples from individuals aged 0-19 years were analyzed using a targeted quantitative metabolomics approach, combining direct injection with reverse-phase liquid chromatography mass spectrometry. Samples were stratified by age: infants (0-2 years), pre-teens (10-12 years), and post-pubertal adolescents (16-19 years). Asymmetric dimethylarginine, carnosine, N-acetyl-serine, and quinolinic acid had a negative association with age, whereas creatinine, homoarginine, lysoPC a C16:1, guanidoacetic acid and 5-Hydroxyindoleacetic acid had a positive association with age. Comparisons between the pre-teen and infant age groups yielded the greatest number of differences followed by the post-pubertal versus infant and post-pubertal versus pre-teen groups. These findings demonstrate age-associated heterogeneity in the pediatric plasma metabolome. Establishing normative reference ranges for metabolite concentrations will be essential to improve the accuracy of metabolomic analyses that include pediatric participants.