Figure 2.

Molecular mechanisms of MSC senescence during aging. Several molecular mechanisms are associated with MSC senescence. DNA damage is a common underlying cause of MSC senescence in which the DNA damage response pathway is activated to block cell cycle progression and delay proliferative arrest. Telomeres gradually shorten with every cell division. Shortening of telomeres can induce cell cycle arrest and apoptosis of MSCs. Cellular senescence occurs when telomeres reach a critical length. The accumulation of dysfunctional mitochondria is associated with an increase in oxidative stress in senescent MSCs. Mitochondrial dysfunction results in an accumulation of ROS, which leads not only to MSC senescence on its own but also to their senescence by impairing mitophagy. ROS increases in aged MSCs, overproduction of endogenous ROS, and oxidative stress damage create a positive feedback loop. Autophagy is responsible for clearing damaged proteins and organelles and maintaining and enhancing MSCs function during aging. Autophagy dysregulation will promote MSC senescence. ROS, reactive oxygen species.