Researchers employ o-vanillin and RG-7112 in sparc–/– mice, targeting accumulated senescent cells in intervertebral discs. Oral administration clears these cells, lowers SASP-driven inflammation, improves vertebral bone quality, and reduces pain marker expression in the spinal cord through p53/MDM2 inhibition and senomorphic activity.

Key points

• Oral o-vanillin and RG-7112 synergistically clear senescent cells in sparc–/– mouse discs.
• Senolytic treatment markedly reduces SASP factor release and local inflammation in IVD tissue.
• Cleared senescence correlates with lower disc degeneration scores and restored ECM integrity.
• Vertebral bone quality improves, and expression of spinal cord pain markers decreases post-treatment.
• RG-7112 blocks p53/MDM2 interaction to induce senescent cell apoptosis; o-vanillin acts as a senomorphic agent.

Why it matters: By demonstrating that targeted senolytic therapy can reverse established disc degeneration and alleviate chronic back pain, this study shifts the paradigm from symptomatic management to disease modification. It highlights a translational pathway for combining natural senomorphics with targeted apoptosis inducers to tackle age-related disorders driven by cellular senescence.