Protein Redox-Regulation Mechanisms in Aging

Abstract

The perspicuity of the general mechanisms of in vivo protein oxidation was achieved in the 1980s and that of the redox-homeostasis mechanisms of reactive oxygen species (ROS)/antioxidants in the 1990s. Publications in the scientific literature dealing with protein redox-regulation mechanisms in aging have appeared only within the past 10-15 years. As is well known, the group of protein disulfide oxidoreductases, such as thioredoxin (Trx), glutaredoxin, and Trx-dependent oxidoreductases, as well as methionine sulfoxide reductase (Msr), and the mechanisms related to these systems work synergistically to regulate the level of oxidized proteins and to repair mildly oxidatively modified proteins, keeping a balanced redox potential to maintain the function of aging cells. The proteolytic enzyme systems such as proteasome complexes, caspases, and the Lon protease, which are regulated by redox mechanisms, eliminate oxidized proteins. These mechanisms, in turn, affect redox homeostasis of proteins in aging cells. The ubiquitination and sumoylation of proteins are other mechanisms by which selectively oxidized proteins are targeted for degradation and compartmentalization with such specificity believed to be necessary for maintenance of cellular redox homeostasis. However, some of the extensively oxidized proteins of an unrepairable nature can escape degradation pathways and form high-molecular-weight aggregates that accumulate with age. Such oxidized protein aggregates can become cytotoxic and have been associated with a large number of age-related disorders, including Alzheimer's disease, Parkinson's disease, cataractogenesis, and cancer. Considering the variations that have emerged in redox-regulation mechanisms and antioxidant systems related to age-related disorders, it is found that these are of an extremely complex nature. Work communicated to us in the current scientific literature now shows the extent of oxidative protein damage in aged subjects and in age-related disorders. Future research will probably be concerned with understanding the relationship between the aforementioned redox-regulatory proteins and age-related disorders. Such scientific progress will bring preventive and therapeutic approaches to control altered redox homeostasis in these disorders.