Redox Research

Tamao Endo, Ph.D.

Toru Sasaki, Ph.D., Tadashi Shinkai, Ph.D., Takao Kaneko, Ph.D.

aging, oxidative stress, free radicals, reactive oxygen species, antioxidative defense systems, growth hormone, metabolic rate, life span, anti-aging interventions

2. Mechanism of age-dependent increase in oxidative stress and development of interventions to decelerate the oxidative stress

3. Relation between reactive oxygen species production and body mass, and energy metabolism

4. Hormonal regulation of energy metabolism and antioxidative defense

5. Effect of adipose tissue on aging and longevity

6. Mechanism of reactive oxygen species production in acute ischemic stroke and reperfusion, and development of antioxidative therapy
 

 The aging process and life span may be controlled by certain genes, and they are also affected by oxidative stress. Since Harman proposed the “free-radical theory of aging”, oxidative stress is postulated to be a major causal factor of senescence. Reactive oxygen species (ROS) and free radicals, the causes of oxidative stress, are derived by the external causes (chemicals, foods, radiation, etc.), as well as the internal ones such as ischemia-reperfusion, xanthine oxidase, mitochondrial electron transport chain, cyclooxygenase, polymorphonuclear leukocytes NADPH oxidase, and myeloperoxidase. Mitochondria are one of the main sources of ROS, because molecular oxygen is metabolized within mitochondria, and almost all of total oxygen is converted to H₂O by 4-electron reduction, while small amount of total oxygen is converted to ROS as byproducts even under normal conditions. ROS and free radicals may be not only harmful, but also essential molecules for life. Recent reports indicate that ROS and free radicals could be kinds of chemical messengers to play important roles in cell signaling, a process termed redox signaling. Indeed, we have indicated that reactive oxygen production itself increased with aging, and the rate of age-related increases was inversely related to the maximum life span of the animals (Fig. 1,2). We have also found that the Spontaneous Dwarf Rat, a growth hormone deficient strain of SD rat, shows longer life span than SD(Fig. 3) and upregulated antioxidative defense systems.

 Oxidative stress status in tissues depends on the valance among ROS and free radicals production, decomposition, and repair of oxidative damages. However, it is not clear that which factor is more critical for explanation in age-related increase of oxidative damages(Fig. 1). In order to clarify the factor, we analyze the various parameters of oxidative stress in aging process. The relation between ROS production and body mass, and energy metabolism are also study to verify “the rate of living and free-radical theories of aging”. For this purpose, we also develop new methodologies to analyze the parameters in oxidative stress. For our goal, the regulation of the age-related increases of ROS and free radicals production and oxidative damages is expected as a potent strategy for anti-aging interventions.