Longevity & AgingSIRT1 Acts as a Master Switch Protecting the Heart Across Multiple Disease States
SIRT1, a NAD+-dependent deacetylase, functions as a metabolic rheostat in the heart, orchestrating protection against oxidative stress, inflammation, apoptosis, ferroptosis, and mitochondrial dysfunction. This review synthesizes preclinical and clinical evidence across myocardial ischemia/reperfusion injury, heart failure, diabetic cardiomyopathy, cardiac hypertrophy, and aging-related dysfunction. Natural compounds including resveratrol, quercetin, curcumin, and ginsenosides, as well as synthetic activators like SRT1720, show preclinical promise by boosting SIRT1 activity. Critically, SIRT1 exhibits dose-dependent duality: moderate activation is cardioprotective, while excessive expression can be harmful. Future strategies must integrate precision medicine, multi-omics, and cardiac-specific delivery to safely harness SIRT1's therapeutic potential.
