SIRT1 in Liver Diseases: Mechanistic Insights and Therapeutic Prospects

Liver diseases present a formidable global health challenge and rank among the leading causes of morbidity and premature mortality worldwide. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylase, has emerged as a crucial regulator of various pathophysiological processes, including metabolic homeostasis, inflammatory responses and apoptosis. This evolutionarily conserved enzyme exhibits a disease‑specific expression profile and is subject to tightly regulated mechanisms in diverse liver diseases. In recent years, accumulating evidence has highlighted the critical involvement of SIRT1 dysregulation in the pathogenesis of various liver diseases. In this review, we provide a comprehensive overview of the roles of SIRT1 in multiple liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), liver fibrosis, and hepatocellular carcinoma (HCC). We further explore the underlying regulatory mechanisms, aiming to establish a rigorous framework to facilitate the clinical translation of SIRT1-targeted therapeutic strategies.