Caloric restriction, reactive oxygen species, and longevity

Abstract The aging population in developed countries is markedly increasing, and the elongation of life and health spans is an emergent need. An inevitable process in all living organisms is aging, in which oxidative stress plays critical roles. Organ functions gradually decrease, and the prevalence of age-related diseases, including diabetes, cardiovascular diseases, cancer, and neural degenerative diseases, increases. Caloric restriction (CR) is a powerful nongenetic intervention for the aging process, which reduces susceptibility to age-related diseases and extends the life span of many species. Multiple signaling pathways contribute to the beneficial effects of CR. In nutrient restriction, growth and protein synthesis signaling pathways, such as the insulin/insulin growth factor 1 (IGF-1) and target of rapamycin (TOR) pathway, are suppressed. Furthermore, as a metabolic adaptation, AMP-dependent protein kinase (AMPK) and sirtuin signaling pathways are activated. Direct evidence for CR-induced life span elongation in humans is difficult to obtain; however, reductions in susceptibility to age-related diseases by CR have been demonstrated in clinical trials. In this chapter, we outline the beneficial effects of CR in a number of species, including humans, and describe the mechanisms responsible with a focus on oxidative stress.