Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy

-dependent deacetylase, exerting protective effects by inhibiting NF-κB and STAT3, activating Nrf2 and FOXO3, and suppressing TGF-β/Smad. In asthma, SIRT1 attenuates Th2 inflammation, mucus hypersecretion, and airway smooth muscle proliferation; in COPD, it reduces neutrophilic inflammation, alveolar senescence, and protease/antiprotease imbalance. Shared benefits include mitigation of oxidative stress, mitochondrial dysfunction, and extracellular matrix remodeling. However, clinical translation faces critical barriers: cell type-specific SIRT1 effects, pharmacokinetic limitations of current activators, and lack of biomarker-guided strategies. This review examines challenges, compares SIRT1's divergent roles, and evaluates chronotherapy, biomarker-guided selection, and SIRT1 activators. Integration of current evidence and knowledge gaps reveals pathways to personalized SIRT1-targeted therapies for obstructive airway diseases.