Document Type
Article
Publication Date
9-3-2021
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.
Recommended Citation
Novais, Emanuel J; Tran, Victoria; Johnston, Shira N; Darris, Kayla R; Roupas, Alex J; Sessions, Garrett A; Shapiro, Irving; Diekman, Brian O; and Risbud, Makarand V, "Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice" (2021). Department of Orthopaedic Surgery Faculty Papers. Paper 158.
https://jdc.jefferson.edu/orthofp/158
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
34480023
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 12, Issue 1, December 2021, Article number 5213.
The published version is available at https://doi.org/10.1038/s41467-021-25453-2. Copyright © Novais et al.