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.
