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

Author

Listed:
  • Emanuel J. Novais

    (Thomas Jefferson University
    Thomas Jefferson University
    University of Minho
    ICVS/3B’s—PT Government Associate Laboratory)

  • Victoria A. Tran

    (Thomas Jefferson University)

  • Shira N. Johnston

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Kayla R. Darris

    (University of North Carolina School of Medicine
    University of North Carolina, Chapel Hill, NC, and North Carolina State University)

  • Alex J. Roupas

    (University of North Carolina School of Medicine
    University of North Carolina, Chapel Hill, NC, and North Carolina State University)

  • Garrett A. Sessions

    (University of North Carolina School of Medicine
    University of North Carolina, Chapel Hill, NC, and North Carolina State University)

  • Irving M. Shapiro

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Brian O. Diekman

    (University of North Carolina School of Medicine
    University of North Carolina, Chapel Hill, NC, and North Carolina State University)

  • Makarand V. Risbud

    (Thomas Jefferson University
    Thomas Jefferson University)

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.

Suggested Citation

  • Emanuel J. Novais & Victoria A. Tran & Shira N. Johnston & Kayla R. Darris & Alex J. Roupas & Garrett A. Sessions & Irving M. Shapiro & Brian O. Diekman & Makarand V. Risbud, 2021. "Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25453-2
    DOI: 10.1038/s41467-021-25453-2
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    Cited by:

    1. Yonggang Fan & Weixin Zhang & Xiusheng Huang & Mingzhe Fan & Chenhao Shi & Lantian Zhao & Guofu Pi & Huafeng Zhang & Shuangfei Ni, 2024. "Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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