Mechanism of SIRT1-mediated Energy Deprivation (Calorie Restriction and Exercise) Against Sarcopenia

Abstract

BACKGROUND: Sarcopenia is a symptom of muscle aging characterized by mass loss and strength loss. The disorder is the leading cause of fall incapacity/death in the elderly and the great enemy of healthy aging. Energy deprivation (calorie restriction and exercise) is the most effective means against aging and SIRT1 is a key mediator molecule. OBJECTIVE: The article summarizes and analyzes the mechanisms of SIRT1-mediated energy deprivation against sarcopenia/skeletal muscle aging. METHODS: Literature review. CONCLUSIONS: Exercise and Calorie restriction lead to intermittent and continuous energy deprivation in muscle, respectively, which may contribute to some differences in their effects and mechanisms. SIRT1 may reside centrally in energy deprivation against sarcopenia. AMPK/NAD+ is the bridge between energy deprivation and SIRT1 activation. SIRT1 downstream is mainly through four pathways (FOXO1/autophagy, PGC-1α/mitochondrial generation, P53/apoptosis and DNA repair, and NF-κB/inflammation) to antagonize muscle aging/sarcopenia. Future directions to focus on: (1) Difference between the mechanisms of SIRT1 under stresses of exercise and calorie restriction. (2) The role of non-transcription factor targets of SIRT1 such as eNOS, LKB1, etc. 3) Exact division of labor involved in several cellular event molecules simultaneously, such as FOXO1, NF-κB and P53.