A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.
- 2026-05-14
- Renal failure 48(1)
- Qiqi Deng
- Chaonian Li
- Jing Luo
- Mengting Yin
- Shilei Qian
- Li Li
- PubMed: 42135894
- DOI: 10.1080/0886022x.2026.2667561
Study Design
- Type
- Review
- Methods
- Systematic review delineating anti-fibrotic mechanisms of sirtuins and summarizing therapeutic strategies
- Funding
- Unclear
Renal fibrosis represents the common pathological endpoint of chronic kidney disease (CKD) progression, yet effective therapies remain limited. The sirtuins family (SIRT1-SIRT7), NAD+-dependent deacetylases, functions as a critical molecular hub linking metabolism, stress responses, and homeostasis. This review systematically delineates the integrated anti-fibrotic mechanisms of sirtuins: SIRT1, SIRT3, and SIRT6 suppress TGF-β/Smad and Wnt/β-catenin signaling; activate the AMPK/PGC-1α axis to correct metabolic dysregulation; promote autophagy via 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.