Cell Senescence and Senolytic Treatment for Low Back Pain

Low back pain (LBP) is a leading global cause of disability, imposing personal and economic costs that exceed $100 billion annually in the U.S. alone. LBP is often linked to intervertebral disc (IVD) degeneration, with senescent cells (SnCs) playing a key role in its progression. SnCs, which accumulate due to aging and cellular stress, adopt a senescence-associated secretory phenotype (SASP), releasing inflammatory and degenerative factors that drive age-related diseases like LBP. In human IVD tissue and cell cultures, SnCs have been shown to contribute to LBP, and their removal decreases the expression of inflammatory and pain-associated SASP factors. Similarly, Sparc-/- mice , which mimic human IVD degeneration, show SnC accumulation with age. Oral senolytic treatments in these animals reduced LBP, eliminated SnCs from the IVD and spinal cord, and decreased SASP factor release. Additionally, treatment improved vertebral bone quality, reduced IVD degeneration and lowered spinal cord pain marker expression. This study demonstrates that systemic oral senolytic drugs, such as RG-7112 and o-Vanillin, effectively reduce behavioural indicators of LBP, suppress SASP, and mitigate degenerative changes in spinal tissues. Combined treatments yielded more robust therapeutic effects, suggesting senolytics could be a promising novel therapy for LBP and other disorders linked to cellular senescence.