Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain

Although significant advances have been made in the study of the molecular mechanisms controlling brain aging, post-transcriptional gene regulation in normal brain aging has yet to be explored. Our lab recently reported that predominant microRNA up-regulation is observed in liver during aging, with key microRNAs predicted to target detoxification genes. Here we examine the role of microRNA regulation in brain during the normal aging process. MicroRNA microarrays and global proteomic profiling were used to compare the brain tissues of 10-, 18-, 24-, and 33-month-old mice. Our results suggest that: (1) like liver, during aging the brain exhibits predominant microRNA up-regulation, and this trend starts in mid-life; (2) of the 70 up-regulated microRNAs, 27 are predicted to target 10 genes of mitochondrial complexes III, IV, and F0F1-ATPase, which exhibit inversely correlated expression; (3) mice of extreme longevity (33-month old) exhibit fewer microRNA expression changes from 10-month-old levels than do old adult mice (24-month old). We found unique de-regulated microRNAs shared between aging brain and aging liver, as well as brain- vs. liver-specific microRNAs during normal aging.