[2] RS is a state where there are more reducing equivalents compared to reductive oxygen species (ROS) in the form of known biological redox couples such as GSH/GSSG, NADP+/NADPH, and NAD+/NADH.
[3] Reductive stress is likely derived from intrinsic signals that allow for the cellular defense against pro-oxidative conditions.
There are several implications of an excess of reducing equivalents: regulation of cellular signaling pathways by decreasing cell growth responses, modification of transcriptional activity, perturbs disulfide bond formation within proteins, increase of mitochondrial malfunction, decrease in cellular metabolism, and cytotoxicity.
[1][5] The over expression of antioxidant enzymatic systems promote the excess production of reducing equivalents resulting in the depletion of ROS and prompting RS in cells.
[6][7] Although different organelles may each have a different redox status, through probing for factors such as glutathione and hydrogen peroxide (H2O2), it was determined that reductive stress is present in the endoplasmic reticulum (ER) of senescent cells.