Activation of senescence and aging characteristics by mitochondrially generated ROS: How are they linked?

Abstract

This article discusses the molecular mechanism(s) that link oxidative stress (ROS) due to mitochondrial dysfunction to the activation of the ROS-sensitive signaling pathways whose levels of activity promote the development of senescence, aging, longevity, and resistance to oxidative stress. Most significantly, our discussion links ROS generated by mitochondrial dysfunction (ROS) to the activation of the ASK1-signalosome - p38 pathway. Our hypothesis argues that this is a major pathway that promotes physiological senescence, aging and age-associated diseases. We thus conclude that the ASK1-signalosome serves as an ROS-sensory system that regulates the levels of ROS-responsive p38 MAPK signals and serves as a signaling center that mediates the physiological consequences of mitochondrial dysfunction.