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 s pecies (ROS) also serve as signaling agents for inflammation, a systemic de fensive reaction against microbial pathogens and other foreign bodies. Chan ges in the pattern of gene expression through ROS-sensitive transcription f actors give rise to both aging and inflammation phenotypes, Chronic oxidati ve stress and inflammatory reaction also lead to many age-associated diseas es such as atherosclerosis and arthritis. Transcription factors that are di rectly influenced by ROS and proinflammatory cytokines include nuclear fact or kappa B (NF-kappa B), activator protein 1 (AP-1), specificity protein 1 (Sp1), peroxisome proliferator-activated receptors (PPARs) and other member s of the nuclear receptor superfamily. Here we describe the basic component s of the intracellular redox control machinery and their dysregulation with age leading to altered transcription factor function and age-associated pa thophysiology. (C) 2000 Elsevier Science Inc. All rights reserved.