Distinct epigenetic analysis of mRNA 5-methylcytosine in the hippocampi of healthy young and aged mice

Abstract Objectives To profile the mRNA m 5 C modification landscape in hippocampi from young and aged mice. Methods MeRIP-seq (Methylated RNA Immunoprecipitation Sequencing) technology was conducted to profile m 5 C-tagged peaks and genes in young and aged hippocampi. M 5 C methylation-related enzymes were detected using Western blot. Results The numbers of m 5 C methylation peaks and genes were increased during aging. Among 2010 different m 5 C peaks, 830 methylated peaks in 782 genes were upregulated and 1,180 methylated peaks in 1,088 genes were downregulated in the aged hippocampi. Most of the m 5 C sites in the hippocampal transcriptome were distributed at the coding sequence, while the fewest m 5 C sites found in the 5′ untranslated regions (5′ UTRs). Young and aged mice showed a similar enrichment of the most credible motif. The protein level of the m 5 C demethylase TET2 was downregulated during aging, suggesting that TET2 may potentially influence neuronal health and even cognitive function through epigenetic mechanisms. Conclusions Our data demonstrated different m 5 C-enriched regions in the young and aged hippocampi, providing novel insight into the possible functions of m 5 C methylation in brain aging.