DBA/2-mdx mice receiving dasatinib plus quercetin demonstrated that senescent cell clearance effectiveness depends critically on treatment timing and target tissue. In skeletal muscle, senescent cells peaked early (3-5 months) during active degeneration phases, while cardiac senescence emerged later (12 months) alongside fibrosis development. Early senolytic intervention reduced skeletal muscle fibrosis and improved contractile performance, but late treatment only benefited cardiac tissue without rescuing skeletal muscle pathology. This temporal specificity of senescence represents a paradigm shift for Duchenne muscular dystrophy therapeutics. Current DMD treatments focus primarily on dystrophin replacement or anti-inflammatory approaches, largely ignoring the senescence burden that drives chronic tissue damage. The tissue-specific senescence patterns suggest that optimal therapeutic strategies may require sequential or targeted senolytic interventions rather than uniform approaches. However, translating these mouse model findings to human DMD patients faces significant challenges, including the compressed disease timeline in rodents versus decades-long human progression. The study's reliance on a single senolytic combination also limits broader therapeutic conclusions, though the mechanistic insights into senescence dynamics provide valuable targets for future drug development in muscular dystrophies.