Senescence dynamics define therapeutic windows for Duchenne muscular dystrophy in DBA/2-mdx mice

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder marked by progressive muscle degeneration and regeneration, inflammation and fibrosis. Cellular senescence has emerged as a potential driver of chronic muscle damage, yet its temporal dynamics and therapeutic relevance remain unclear. We analyzed senescent cell burden in skeletal and cardiac muscle of the DBA/2-mdx mouse model, which closely mimics many features of human DMD. The senolytic combination of dasatinib and quercetin (D+Q) was administered during early or late disease phases to evaluate the impact of senescent cell clearance. Skeletal muscle strength was measured by grip strength and ex vivo force assays, while cardiac function was assessed by echocardiography. Fibrosis and senescence markers were quantified histologically, and bulk RNA sequencing (RNA-seq) was used to identify transcriptional changes associated with senolysis.