Nutrient-sensing pathways in adult stem cells: Orchestrating homeostasis, aging, and disease.

Nutrient-sensing pathways, including mTOR, AMPK, Sirtuins, and insulin/IGF-1 signaling, are central regulators orchestrating adult stem cell (ASC) fate by dynamically modulating cellular metabolism. This review proposes a framework that integrates these pathways into a cohesive network that dictates the metabolic transitions between quiescence, activation, and differentiation in ASCs. Age-related dysregulation of this network leads to metabolic imbalance and stem cell exhaustion, underpinning tissue degeneration. Interventions such as mTOR inhibitors, AMPK activators, NAD+ precursors, and dietary strategies can rejuvenate ASC function by restoring metabolic balance, underscoring their therapeutic potential for mitigating aging and associated diseases.