Oxidative Stress Biomarkers and Senescence-Related Gene Expression in Human Lumbar Degenerative Disc Disease

Background: Oxidative stress is increasingly recognized as a key driver of lumbar degenerative disc disease (LDDD), promoting inflammation, extracellular matrix degradation, and cellular senescence. However, studies integrating oxidative stress biomarkers with senescence-related gene expression in human intervertebral discs remain limited. Methods: Thirty-two patients undergoing lumbar spine surgery were prospectively enrolled, yielding 36 surgically obtained intervertebral disc specimens. Thirty patients with symptomatic LDDD comprised the study population, while two patients with Pfirrmann grade I discs served exclusively as laboratory controls. Specimens were classified as mild (Pfirrmann grades II–III) or severe degeneration (grades IV–V). Due to tissue availability, RT-qPCR analyses were performed on 34 specimens, whereas oxidative stress biomarkers were evaluated in 32 specimens. Oxidative stress was assessed by measuring sulfhydryl protein levels and nitric oxide production, while the expression of NF-κB, GSK3β, and P21 was quantified by RT-qPCR. Results: Severely degenerated discs showed significantly lower sulfhydryl protein levels than mildly degenerated discs (p = 0.009), indicating impaired antioxidant defense. P21 ΔCq values were significantly higher in severe degeneration, indicating lower relative P21 expression (p = 0.038), whereas NF-κB and GSK3β showed no significant differences between degeneration groups. Significant positive correlations among NF-κB, GSK3β, and P21 suggested coordinated variation in these molecular pathways. Nitric oxide levels tended to be higher in severe degeneration but were not significantly different. Conclusions: Advanced LDDD was associated with impaired antioxidant capacity and lower relative P21 expression. Reduced sulfhydryl protein levels and altered P21 expression support an association between oxidative stress, senescence-related pathways, and disc degeneration.