FIG. 2.

Schematic changes in the resolution of redox switches with age. Increases in O₂^−•/H₂O₂ production in postreproductive adults cause both reversible and irreversible modifications in protein thiols. Reaction kinetics of thiol reduction will vary as a function of the degree of oxidation of both the target protein thiols as well as the Trxs/Grxs/Srxs that reduce the oxidized thiols belonging to the target proteins. Thus, the reduction of Prx S-S or Prx SOH by Trx or GSH+GST is considerably faster than the reduction of Prx SO₂H by Srx (39, 92, 94). The heights of the curved arrows represent the relative rate of resolution of these post-translational modifications as a function of the increasing pro-oxidizing state that accompanies age. Components of the redox system are themselves subject to inactivation via oxidation of functional thiols, further enhancing the disruption of these redox switches. Grx, glutaredoxin; GST, glutathione-S-transferase; Srxs, sulfiredoxins.