Research Paper Volume 1, Issue 9 pp 784—802

Figure 1. The Trx-ASK1 pathway of ROS mediated regulation of the p38 MAPK stress response pathway. The proposed hypothesis states that (a) the increased level of mitochondrial generated ROS in aged tissues/cells results in a locked-in cycle of ROS production and the amplification of oxidative stress signaling (p38 MAPK/SAPK-JNK). The chronic increase of endogenous levels of ROS stabilizes the increased basal, intrinsic changes in activity of regulators of the stress response which is the basis for the development of a state-of-chronic-stress and progressive decline in tissue function. (b) Longevity and resistance to oxidative stress is associated with the elevated levels of the (SH)₂Trx-ASK1 complex which attenuates the activity of stress response signaling pathways (p38 MAPK/SAPK-JNK). The levels of the (SH)₂Trx-ASK1 complex decrease as the levels of endogenous ROS increase in aging tissues. In long-lived mouse models the levels of the complex are elevated and part of the resistance to oxidative stress.