Role of redox-regulated transcription factors in inflammation, aging and age-related diseases.

A progressive rise of oxidative stress due to the altered redox homeostasis appears to be one of the hallmarks of the aging process. Reactive oxygen species (ROS) also serve as signaling agents for inflammation, a systemic defensive reaction against microbial pathogens and other foreign bodies. Changes in the pattern of gene expression through ROS-sensitive transcription factors give rise to both aging and inflammation phenotypes. Chronic oxidative stress and inflammatory reaction also lead to many age-associated diseases such as atherosclerosis and arthritis. Transcription factors that are directly influenced by ROS and proinflammatory cytokines include nuclear factor kappa B (NF-kappaB), activator protein 1 (AP-1), specificity protein 1 (Sp1), peroxisome proliferator-activated receptors (PPARs) and other members of the nuclear receptor superfamily. Here we describe the basic components of the intracellular redox control machinery and their dysregulation with age leading to altered transcription factor function and age-associated pathophysiology.