MTOR and nutritional deficiency disease: CLIS drives malnutrition through two synergistic mechanisms: (1) overexpression of pro-inflammatory cytokines that dysregulate hypothalamic appetite control (manifesting as the “anorexia of aging” phenotype) (40), and (2) concurrent activation of ubiquitin-proteasome-mediated proteolysis and suppression of anabolic pathways like mTOR signaling, leading to systemic protein depletion (4).