Fig. 3
From: Epigenetic regulation of satellite cell fate during skeletal muscle regeneration
Senescence mediated by irreversible cell cycle arrest caused by p16INK4a expression in sarcopenic MuSCs. In young and old MuSCs, the presence of PRC1 complex containing RING1 and BMI1 subunits leads to H2A ubiquitination at the promoter of INK4a locus and the repression of p16INK4a. This repression allows RB protein phosphorylation and loss of stability of E2F/RB complex. Once free from its complex, E2F induces the expression of genes promoting the cell cycle. Sarcopenic MuSCs lose their PRC1 repression of p16INK4a, leading to reduction of RB phosphorylation and maintenance of the E2F/RB complex. Without free E2F protein, the expression of genes promoting cell cycle is reduced, causing cell cycle arrest and senescence of MuSCs