Caloric Restriction, Starvation, and Antiaging Medicine: Caloric Restriction Research and Antiaging

The antiaging effects of caloric restriction, which involves reducing the food given to experimental animals by about 30% and keeping them on this diet for a long period, have been confirmed across various species, from nematodes and fruit flies to mice and monkeys. Therefore, it is considered to be one of the traits that organisms have acquired during the process of evolution. Organisms sense their nutritional status and choose whether to produce the necessary energy using the nutrients they have ingested or to store them for future energy shortages. This is thought to have maximized both the chance of survival of the organism itself and the chance of survival of the species through reproduction. The antiaging effects of caloric restriction are suggested to be closely related to this nutrient-sensing function of organisms, and the center that controls this is thought to be a group of neurons in the arcuate nucleus in the hypothalamus of the brain. Neurons expressing neuropeptide Y (NPY) are known to be important for the antiaging effects of caloric restriction. Activation of NPY enhances feeding behavior and suppresses energy consumption. Caloric restriction enhances the expression of NPY in the arcuate nucleus. On the other hand, it has been reported that when caloric restriction is applied to NPY knockout mice, their lifespan does not extend, and the antiaging effects of caloric restriction, such as enhanced oxidative stress resistance and reduced tumor incidence, disappear or weaken [1]. Insulin, leptin, and ghrelin are known to be important factors in the regulation of NPY expression. Insulin is a hormone-like factor secreted from pancreatic β cells, leptin from fat cells, and ghrelin from the stomach. Insulin and leptin negatively regulate the expression of NPY, while ghrelin positively regulates it. It has been reported that animals subjected to caloric restriction have decreased body weight and blood glucose levels, along with decreased blood insulin and leptin concentrations and increased ghrelin concentration.