Oxidative Stress and Antiaging Medicine: Antiaging through Antioxidation

Reactive oxygen species include superoxide, which is oxygen reduced by one electron at a time, hydrogen peroxide, hydroxyl radicals, and singlet oxygen, which is excited oxygen. Also, hypochlorous acid produced from hydrogen peroxide and chlorine ions, peroxynitrite, a reaction product of nitric oxide and superoxide, lipid hydroperoxides and lipid peroxyl radicals produced by lipid oxidation, are recognized as reactive oxygen species in a broad sense. These reactive oxygen species do not necessarily harm the body, and it is known that an appropriate concentration of reactive oxygen species functions as a signal in the body. For example, it is known that reactive oxygen species produced in mitochondria cause epigenetic changes to nuclear DNA, which in turn act to extend lifespan. On the other hand, the body has an antioxidation mechanism to prevent oxidative damage by reactive oxygen species. Oxidative stress is a state where the balance between oxidative power and antioxidative power is disrupted, leaning towards the former, and can be understood as a state where “the production of reactive oxygen species increases, damage to the body accumulates to an irreparable extent, and damage to bodily functions occurs.” The theory that supported the relationship between oxidative stress and aging is the “oxidative stress hypothesis of aging,” proposed by Dr. Denham Harman in 1956. Unfortunately, the current situation is a mix of studies that support and do not support this theory, and a consensus on oxidative stress and aging in higher animals such as humans, monkeys, and mice has not yet been reached. However, in the case of Caenorhabditis elegans (C. elegans), which is frequently used as a model organism, it has been proven that oxidative stress is involved in aging [1]. Specifically, a mutant that shows a reduction in lifespan depending on the oxygen concentration was isolated, and the causative gene was identified as cyt-1, a subunit of mitochondrial electron transport complex II. This gene is conserved in humans as succinate dehydrogenase complex subunit C (SDHC). Interestingly, mice introduced with a mutant SDHC gene with a similar mutation show symptoms related to aging, such as neurological damage and infertility. In this section, we will discuss antioxidation and anti-aging, including research examples in model organisms such as C. elegans, and the current status and future prospects.