Transcriptome-wide profiling of m6A modifications in the mouse embryonic fibroblasts (MEFs) replicative senescence

Nonetheless, the roles of m6A modification in aging research was still rarely reported. Herein, we uncovered that the m6A modification level and the methyltransferase Mettl3 expression level were significantly enhanced in aging process, including physiological aging mice model, cellular replicative senescence model.

Furthermore, silencing of Mettl3 staved off senescent phenotype of MEF cells, as evidenced by down-regulation of p16, decreased β-galactosidase activity and enhanced cell proliferative capacity, while Mettl3 overexpression accelerated the cellular senescence. Results of in vivo experiments showed that Mettl3 overexpression mice exhibited more pronounced senescence phenotype accompanied with shortened lifespan. To deepen into the understanding of the molecular mechanism of m6A and Mettl3 on aging process, the high throughput MeRIP sequencing was performed in the young or senescent MEFs