Dietary modulation of prostanoid synthesis in the aging process: role of cyclooxygenase-2

To investigate the role of cyclooxygenase (COX) as a mediator for prostaglandin synthesis in relation to generation of reactive oxidant species (ROS), we quantitated the COX-derived ROS generation and the gene expression of COX-2, an inducible form of COX in aged kidney. In addition, the modulation by dietary restriction was investigated. COX-derived ROS generation increased with age in ad libitum (AL) rats, but dietary restriction (DR) suppressed the level. The amounts of COX-2 protein and mRNA increased with age in AL rats but maintained at low levels in DR group. It was found that the binding characteristics of a nuclear transcription factor, NF-kappa B were altered by aging. The binding activity of NF-kappa B in aged kidney was significantly enhanced with the corresponding increase in mRNA and protein levels. These increases were closely in parallel to the increased ROS generation and gene expression of COX-2. The COX activity shown by NF-kappa B activation and the ROS generation by COX-mediated process were all modulated by DR. Our results suggest that the upregulation of COX-2 during aging may play an important role in many age-related diseases associated with aging process. And this upregulation was attenuated by DR. We propose that the modulation of the redox-sensitive transcription factor may well be a part of the mechanisms underpinning the anti-oxidative action of DR. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.