Figure 3. The interplay between senescence and apoptosis is cell type specific.

The pathways leading to apoptosis are depicted in red, those leading to apoptosis resistance in orange, and those that sensitize endothelial cells to apoptosis in blue. (A) Senescent fibroblasts are resistant to p53-mediated apoptotic stimuli, such as actinomycin D and low-dose cisplatin, as well as to stimuli—such as staurosporine—that rely on p53 target genes. This resistance can be explained by low p53 levels due to decreased stabilization in senescent cells, as well as the existence of senescence-specific p53 post-translational modifications. Senescent and non-senescent cells have a similar sensitivity to p53-independent apoptotic stimuli. (B) Senescent endothelial cells have increased sensitivity to apoptosis. Senescent endothelial cells lose eNOS expression and express reduced levels of pro-survival NO. This eNOS loss may be due to the loss of the positive regulator AKT, or to the upregulation of negative regulators, such as caveolin-1. However, AKT levels increase during replicative senescence, so the issue of PTEN/PI3K/AKT signaling in the senescent endothelium is unresolved. See Glossary for definitions and the text for details.