Our studies have described a mechanism that links mitochondrial-generated ROS to the activation of stress induced aging phenotypes and that the ROS-responsive ASK1-signalosome regulates the p38 MAPK pathway activity and its downstream targets of senescence and aging, e.g., p16Ink4a, p19Arf, TNFα, JNK, apoptosis and cardiovascular diseases (Figure 1 and Figure 6). The gene discussed is MAP3K5; the disease is cardiovascular disorder.