Senolytic Therapy as a Preventive Strategy for Low Back Pain

Abstract

Cell senescence drives inflammation and tissue breakdown and is a key hallmark of aging. Low back pain is strongly linked to age-related degeneration of spine tissues, and with an accumulation of senescent. Here we show that preventive administration of the senolytic agents o-vanillin and RG-7112 prevent the development of pain-related behaviour in young sparc-/- mice. Treated mice exhibit a reduction 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. This early senolytic intervention also preserves intervertebral disc volume and vertebral bone microarchitecture, indicating protection against structural degeneration of the spine. 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.