Fig. 2

A model for programmed increase in reactive oxygen species and altered transcription factor function during aging

The model postulates that the cellular level of reactive oxygen species (ROS) gradually rises because of corresponding increases in membrane-associated oxidative enzymes such as NADPH oxidase, lipoxygenase, and cyclooxygenase. Intracellular rise in ROS can then activate NF-κB and initiate a subchronic inflammatory response. Furthermore, besides causing random oxidative damage to intracellular proteins, ROS can preferentially inactivate certain redox sensitive trans-acting factors such as cMyb (65), IRE-BP (iron response element binding protein) (66), Sp1 (19), and HSF-1 (35,36), with deleterious consequences to cell function. Although for the sake of simplicity, lipoxygenase/NADPH oxidase/cyclooxygenase are all depicted together, these enzymes have been localized in the following membrane fractions: lipoxygenase, plasma membrane, and nuclear membrane (59); NADPH oxidase, plasma membrane (61); cyclooxygenase, endoplasmic reticulum, and nuclear membrane (60).