Under conditions of calorie restriction, i.e. at reduced food intake, the lifespan of model organisms, such as yeast, worms or flies, is increased. Similarly, when the activity of nutrient-sensing pathways is reduced by the knockdown of one or several of their key genes, these species live longer. Even in rodents and rhesus monkeys decreased nutrient-sensing pathway activity or calorie restriction protects them against T2D, CVD and cancer. The molecular basis of these processes are sensing of glucose and amino acids via the insulin/IGF and the TOR pathways, respectively, and the integration of the nutritional and energetic status of cells and tissues via HDACs of the sirtuin family and AMPK. Since these signal transduction pathways are evolutionary conserved, also humans may be protected against age-related pathologies. Humans may slow down their aging process, when their nutrient signaling pathways are modulated by moderate intake of a diet that was personalized for them.
In this chapter, we will get insight into the evolutionary conservation of nutrition-sensing pathways and their relation to the aging process. We will realize that higher organisms, such as mammals, use more complex regulatory circuits for sensing food that involve the CNS via the growth hormone endocrine axis. However, a detailed view on signal transduction related to calorie restriction will show us that even for humans very similar regulatory principles apply. We will discuss this insight and its potential application in preventing of age-related diseases and promoting healthy aging in humans.