Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice
| Autor: | Shira N. Johnston, Irving M. Shapiro, Brian O. Diekman, Makarand V. Risbud, Victoria A. Tran, Kayla R. Darris, Garrett A. Sessions, Alex J. Roupas, Emanuel J. Novais |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Senescence
Programmed cell death Aging Nucleus Pulposus Cell Survival Science Dasatinib General Physics and Astronomy Degeneration (medical) Intervertebral Disc Degeneration Pharmacology General Biochemistry Genetics and Molecular Biology Article Mice Fibrosis medicine Back pain Animals Aggrecans Senolytic Cellular Senescence Inflammation Multidisciplinary Musculoskeletal system business.industry Annulus Fibrosus Intervertebral disc General Chemistry medicine.disease Extracellular Matrix Mice Inbred C57BL medicine.anatomical_structure Phenotype Quercetin medicine.symptom business Transcriptome medicine.drug |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2041-1723 |
| Popis: | 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. Intervertebral disc degeneration is a leading cause of chronic back pain and disability. Here the authors show that long term treatment with senolytic compounds Dasatinib and Quercetin reduces disc senescence burden and ameliorates age-dependent degeneration in mice. |
| Databáze: | OpenAIRE |
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