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-kappaB were altered by aging. The binding activity of NF-kappaB 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-kappaB 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.