Reversine ameliorates hallmarks of cellular senescence via reactivation of autophagy and insulin sensitivity in human skeletal myoblasts

Cellular senescence leads to depletion of myogenic progenitors and decreased regenerative capacity. We show that the small molecule 2,6-disubstituted purine, reversine, can improve some well-known hallmarks of cellular aging in senescent myoblast cells. Reversine reactivated autophagy and insulin signaling pathway via up-regulation of AMP-activated protein kinase (AMPK) and Akt2, restoring insulin sensitivity and glucose uptake in senescent cells. Reversine also restored the loss of connectivity of glycolysis to the TCA cycle thus restoring dysfunctional mitochondria and the impaired myogenic differentiation potential of senescent myoblasts. Collectivity, our data suggest that cellular senescence can be reversed with small molecule without reprogramming to the pluripotent state.