Fig. 3.

A: schematic representation of the redox signaling pathways that are postulated to lead to adaptive activation of transcription factors and upregulation of the expression of cytoprotective proteins following contractile activity in skeletal muscle. TF, transcription factor. [Redrawn and updated from Jackson and McArdle (35).] B: putative sites at which the redox signaling pathway may be modified in aging leading to a failure of adaptive responses to contractile activity. Excess hydrogen peroxide generated by mitochondria in the muscle during aging may influence the pathway shown in A at multiple points: prevention of activation of NADPH oxidase; a chronic increase in cytosolic hydrogen peroxide; aberrant chronic oxidation of glutathione and other redox sensitive signaling proteins; oxidation of the nuclear environment leading to a failure of TF to activate transcription. AP1, activator protein-1; HSF1, heat shock factor-1; Nrf2, nuclear transcription factor erythroid 2p45-related factor-2.