Therapeutic potential of sulfasalazine for sarcopenia: Insights from mouse models and clinical data

Abstract

Sarcopenia, a disease marked by a progressive loss of muscle mass, increases the risks of disability and metabolic disorders, and decreases quality of life. Current therapeutic options are limited. YY1 transcriptional activity is augmented through an interaction with PHF20 at its promoter region, suppressing muscle differentiation. This study screened sulfasalazine, a medication for managing inflammatory bowel diseases (IBD), using the PHF20-YY1 promoter assay in C₂C₁₂ myoblasts from an FDA-approved drug library. Sulfasalazine effectively inhibited PHF20-induced YY1 promoter activity (IC₅₀ = 24 μM), reducing YY1 expression and enhancing muscle-specific gene expression. In mouse models of muscle atrophy, sulfasalazine not only enhanced muscle strength and function but also mitigated muscle loss. Clinical data from patients with IBD revealed that those treated with sulfasalazine had a significantly higher TPI (total psoas index), used as a muscle mass marker, suggesting enhanced muscle preservation. In conclusion, this study suggests the potential for repurposing sulfasalazine to manage sarcopenia, especially associated with IBD.