Age and Spinal Level as Predictors of Lumbar Disc Degeneration in Humans and Mice: A Comparative Analysis

ABSTRACT Background Aging is a major risk factor for IVD degeneration and chronic lower back pain. Comparing degenerative patterns in human and mice, a commonly used pre‐clinical model, is crucial for validating it in preclinical mechanistic research. The goal of the study was to compare the effect of age and spine level on degeneration in human and mouse lumbar IVDs . Methods T2 ‐weighted MRI images of human lumbar spine were graded using the Pfirrmann system. H&E‐stained mid‐coronal sections of mouse lumbar IVDs were scored using the Melgoza and Chenna system. Age, gender, IVD level, and lumbar IVD degeneration scores, respectively, were used for statistical analysis in each species. Linear regression and one‐way ANOVA with post hoc Tukey analysis were used to compare regression slopes and intercepts. Age conversion from mouse to human was performed according to the Jackson Laboratory's outline of mouse age and its human equivalents. Generalized estimating equations ( GEE ) were used to model continuous degeneration scores, accounting for intra‐subject correlation due to multiple IVD levels per subject. Main effects included sex, IVD level ( L1 – S1 ), and age, with an interaction term assessing the impact of age across levels. An autoregressive correlation structure was specified. Results Age significantly correlated with IVD degeneration in humans ( p < 0.0001) and mice ( p < 0.0002). And the IVD level predicted degeneration in both species ( L5 – S1 in human, and L6 – S1 in mice). Normalizing age and pathology revealed an earlier onset of degeneration in humans than in mice. Conclusions Age and spinal IVD level influence lumbar IVD degeneration in both human and mice with a higher rate of degeneration at the lumbosacral junction in both species. These findings suggest that mice are a suitable model for studying the cellular and molecular basis of IVD degeneration and associated neurological symptoms, with the L6 – S1 level being the most relevant.