Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver

Clin Pharmacol Ther. 2015 Aug;98(2):205-15. doi: 10.1002/cpt.145.


Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all, 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n = 10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1,000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Biotransformation / genetics
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Computational Biology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Infant
  • Liver / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Pharmacogenetics*


  • MicroRNAs