title: The role of COX-2 and Nrf2/ARE in anti-inflammation and antioxidative stress: Aging and anti-aging.
abstract: Oxidative stress and inflammation are constant features of many chronic diseases and complications, and have been linked to carcinogenesis. Cyclooxygenase 2 (COX-2), a rate-limiting enzyme for the synthesis of prostaglandins, plays important roles in physiology and pathology, but has been a source of controversy within the scientific and clinical community. However, recent work has shown that nuclear factor erythroid-2-related factor-2 (Nrf2) confers protection against oxidative stress. Furthermore, COX-2-dependent electrophile oxo-derivative (EFOX) molecules have been shown to act as anti-inflammatory mediators via activation of the Nrf2-dependent antioxidant response element (ARE). These studies have provided more insight into COX-2-mediated events. The function of all tissues, especially epithelial and endothelial tissues, declines with age, leading to the production of reactive oxygen species (ROS). COX-2 expression increases with aging in most tissues, due in part to ROS, chemical reactions, physical shearing, and dietary molecules. Here we discuss new findings related to COX-2 inflammatory and anti-inflammatory responses. Taken together, we hypothesize that COX-2 levels increase during the aging process because increasing levels of ROSs necessitate the involvement of COX-2-dependent EFOXs for anti-inflammation and Nrf2/ARE signaling for antioxidation. We also propose that COX-2 may act as an intrinsic biological aging clock due to its role in balancing inflammatory and anti-inflammatory responses.
authors.affiliation: Department of Biotechnology, University of Tartu, Riia 23, Tartu 51010, Estonia. Luo58@yahoo.com
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Egon
authors.initials: E
authors.lastname: Urgard
authors.forename: Tõnu
authors.initials: T
authors.lastname: Vooder
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
mesh_terms: D000375:Aging / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human