Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

Abstract Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence(definition), we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts showed lower incidences of degeneration, and the treatment resulted in a significant decrease in senescent markers p16 INK4a , p19 ARF , and SASP molecules IL-1β, and IL-6. Treated animals also showed preserved cell viability, phenotype, and matrix content. Although transcriptomic analysis showed disc compartment-specific effects of the treatment, cell death and cytokine response pathways were commonly modulated across tissue types. Results suggest that senolytics(definition) may provide a novel approach to mitigating age-dependent disc degeneration.