The dasatinib-quercetin (DQ) senolytic combination significantly reduced cellular senescence markers including p19ARF, p21, and inflammatory SASP proteins in mouse intervertebral discs, while preserving cell viability and preventing tissue fibrosis. Transcriptomic analysis revealed the treatment modulated JUN signaling pathways and cell cycle regulation across disc tissues, with effects confirmed in human degenerated disc cells. This represents a notable advance in translating senolytic therapy from general aging research to specific musculoskeletal applications. The finding addresses a major clinical need since disc degeneration affects over 80% of adults and current treatments only manage symptoms rather than underlying cellular pathways. However, the study's reliance on a genetically susceptible mouse strain and short treatment duration limit immediate clinical translation. The identification of shared molecular targets between mouse and human disc cells strengthens therapeutic relevance, but safety concerns around systemic senolytic administration—including potential effects on beneficial senescent cells and tissue regeneration—require extensive investigation before human trials can proceed.