Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain.

Cellular senescence drives inflammation and tissue breakdown and is a key hallmark of aging. The accumulation of senescent cells is strongly linked to the degeneration of spinal tissues and back pain. Here, we show that administration of the senolytic agents, o-vanillin and RG-7112, prevents the development of pain-related behavior in sparc-/- mice. Treated mice exhibit a reduced expression of senescence markers in the intervertebral discs, vertebral endplates, vertebral bone, and spinal cord, alongside a dampening of pro-inflammatory senescence-associated secretory factors in these tissues. Early senolytic intervention also preserved intervertebral disc volume and vertebral bone microarchitecture, indicating protection against structural spine degeneration. These findings demonstrate that targeting cellular senescence at an early stage can mitigate degenerative changes and pain, supporting senolytic therapy as a promising preventive strategy for musculoskeletal decline.