Regulation of aging by balancing mitochondrial function and antioxidant levels.

Abstract

Aging is the deterioration of physiological mechanisms that is associated with getting old. There is a link between aging and mitochondrial function. In C. elegans, it has been reported that inhibiting the electron transfer system decreases ATP production and extends lifespan. However, it has also been suggested that energy loss due to mitochondrial dysfunction or impairment is a mechanism of diseases and aging. Thus, there is an unresolved relationship between ATP levels and aging. To address this issue, we administered febuxostat (FBX), an inhibitor of human xanthine oxidase (XO)/xanthine dehydrogenase (XDH), to C. elegans. XO/XDH is an enzyme that participates in the in vivo synthesis of uric acid. When FBX is added to cells, the salvage pathway of purine metabolism becomes dominant, and the ATP concentration increases. Since humans and C. elegans but few mammalian species lack uricase, which degrades uric acid, we used C. elegans as a model to evaluate the effects of FBX and to challenge the enigma of the relationship between ATP and lifespan.In this study, we showed that FBX protects mitochondria and prevents age-related muscle deterioration in C. elegans. In addition, we showed that FBX administration could increase ATP levels without overloading the mitochondria while extending the lifespan. We also showed that the combination of FBX and an antioxidant as a protection against ROS prolongs lifespan more. We have shown that the antioxidant effects and increased ATP levels may lead to antiaging effects.