Nutritional Signaling and Aging
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In this chapter, we will present the evolutionary conservation of nutrition-sensing pathways and their relation to the process of aging. Mammals use more complex regulatory circuits for sensing food, which involve the CNS via the GH1 endocrine axis. The molecular basis of this is the sensing of glucose and amino acids via insulin/IGF and the TOR pathways, respectively, and the integration of the nutritional and energetic status of cells and tissues via sirtuins and AMPK. The insulin signaling axis is composed of a number of critical nodes including the receptor IR, the adaptor protein IRS, the kinases PI3K and AKT as well as the transcription factor FOXO1. We will analyze the mechanisms how this central signal transduction pathway interacts with environmental challenges mediated via multiple other pathways, in order to keep cells and tissues in homeostasis. Under conditions of calorie restriction, i.e., at reduced food intake, the lifespan of model organisms, such as yeast, worms or flies, is increased. Interestingly, signal transduction pathways related to calorie restriction show also in humans very similar regulatory principles. This insight has the potential to prevent age-related diseases, such as T2D, CVDs and cancer, and to promote healthy aging in human.