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

Emanuel J. Novais, Victoria A. Tran, Shira N. Johnston, Kayla R. Darris, Alex J. Roupas, Garrett A. Sessions, Irving M. Shapiro, Brian O. Diekman and Makarand V. Risbud ()
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Emanuel J. Novais: Thomas Jefferson University
Victoria A. Tran: Thomas Jefferson University
Shira N. Johnston: Thomas Jefferson University
Kayla R. Darris: University of North Carolina School of Medicine
Alex J. Roupas: University of North Carolina School of Medicine
Garrett A. Sessions: University of North Carolina School of Medicine
Irving M. Shapiro: Thomas Jefferson University
Brian O. Diekman: University of North Carolina School of Medicine
Makarand V. Risbud: Thomas Jefferson University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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, 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 show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, p19ARF, and SASP molecules IL-6 and MMP13. Treatment also preserves cell viability, phenotype, and matrix content. Although transcriptomic analysis shows disc compartment-specific effects of the treatment, cell death and cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide an attractive strategy to mitigating age-dependent disc degeneration.

Date: 2021
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DOI: 10.1038/s41467-021-25453-2

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