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Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of  P16   INK 4 A   (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for  matrix metalloproteinase-13 ,  ADAMTS 5  (a disintegrin and metalloprotease with thrombospondin motifs 5), and  P16   INK 4 A  . Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of  P16   INK 4 A  . Cells from degenerate discs (even from young patients) exhibited increased expression of  P16   INK 4 A  , increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between  P16   INK 4 A   and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs  in vivo  and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration.

Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration