Fig. 2.

Potential role of mitochondrial apoptosis in aging of long-lived cells. During aging, mitochondrial ROS production steadily increases, leading to DNA damage and the activation of a p53-mediated transcriptional response. p53 transcriptional targets include pro-apoptotic genes such as Bak and Bax. p53 also directly triggers mitochondrial apoptosis by binding to and promoting the oligomerization of pro-apoptotic Bak protein in the outer mitochondrial membrane. Chronic activation of this pathway is likely to negatively impact tissues dependent on non-regenerating long-lived cells, such as the cochlea, brain, and heart.