A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis

FoxO and TFEB; and alleviate oxidative stress and inflammation through Nrf2 and NF-κB modulation. We further summarize diverse therapeutic strategies targeting sirtuins-including natural compounds, traditional Chinese medicine formulations, synthetic drugs, gene therapy, bioactive peptides, and exercise training-that exhibit significant anti-fibrotic efficacy in preclinical models. Despite promising evidence, clinical translation faces challenges including cell-type-specific functional duality, disease-stage-dependent effects, and the need for highly selective modulators with improved bioavailability and renal targeting. This review highlights sirtuins as a multi-dimensional regulatory network and a promising therapeutic frontier in renal fibrosis, while outlining key obstacles and future directions for clinical application.