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Health Sciences › Medicine › Pathology and Forensic Medicine
Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice
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Paper Summary
Paperzilla title
Zombie Cell Slayers: A Dynamic Duo Against Disc Decay (But Time is of the Essence!)
Dasatinib and Quercetin (D+Q), a senolytic drug combination, effectively slowed age-related disc degeneration in mice when administered before the onset of established degeneration. D+Q reduced senescence markers, mitigated inflammation, and preserved disc matrix composition, indicating its potential as a therapeutic strategy for early- to mid-stage disc degeneration.
Possible Conflicts of Interest
None identified
Identified Weaknesses
Limited efficacy in advanced degeneration
The 18-23 M cohort, which began treatment after disc degeneration was established, did not show the same improvement as the 6-23 M and 14-23 M cohorts, which began treatment earlier. This highlights a potential limitation of the treatment in cases of advanced degeneration where therapeutic window has been passed and cellular responsiveness is diminished.
Potential confounding from systemic effects
While the systemic benefits of D+Q treatment are promising, it's essential to acknowledge that they may influence the study's results on disc degeneration. Additional experiments are needed to isolate the direct effects of the treatment on disc health from its systemic effects.
Limited investigation of D+Q mechanism in disc
The study did not perform in-vitro mechanistic studies to fully elucidate how D+Q modulates cellular pathways within the intervertebral disc. This deeper understanding would be crucial for optimizing the treatment strategy.
Rating Explanation
This study demonstrates the potential of D+Q as a senolytic treatment for age-related disc degeneration in mice, providing valuable insights for future therapeutic strategies. It showed that D+Q slowed the progression of disc degeneration when started at early or middle age by reducing senescence, mitigating SASP, and preserving extracellular matrix composition and cell phenotype in the discs. However, it has a limited impact on advanced cases, suggesting a critical window for effective intervention.
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File Information
Original Title:
Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice
File Name:
s41467-021-25453-2.pdf
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July 14, 2025 at 10:37 AM
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