Figure 1: The possibe mechamism by which p53/p21 and p16INK4a modulate MSCs senescence. Oxidative stress and DNA damage induce MSCs senescence by activating the ATM/ATR pathway and Chk1/Chk2 to stabilize p53/p21. Oxidative stress can indirectly induce DNA damage. Oxidative stress and DNA damage can also cause high expression of p16INK4a. Up-regulate the expression of p53/p21 and p16INK4a increase the expression of the active, hypophosphorylated Rb. Activated Rb pathway can make cells enter cell cycle phase arrest that eventually contributes to MSCs senescence.