Abstract: Background: Advanced Glycation End products (AGEs) are implicated in intervertebral disc degeneration (IDD) via oxidative stress, inflammation, and matrix degradation. However, their specific role as nutritional–metabolic modifiers of disc biomechanics remain insufficiently integrated. Objective: This review synthesizes current evidence linking dietary and endogenous AGEs to IDD and proposes a conceptual framework connecting nutrition, matrix glycation, and disc biomechanics. Methods: A focused narrative review was conducted, prioritizing peer-reviewed literature on AGE biology, dietary intake, cellular disc responses, and mechanical alterations. We analyzed studies concerning collagen cross-linking, proteoglycan-dependent pressurization, and endplate transport function. Synthesis: AGEs promote IDD through RAGE signaling, oxidative stress, and senescence, leading to diminished proteoglycan synthesis and matrix metalloproteinase activation. Crucially, AGEs induce a mechanical phenotype shift: they increase annular collagen stiffness, attenuate nucleus pulposus pressurization, and compromise the cartilaginous endplate as a transport–loading interface. Evidence from animal models further confirms a direct pathway from high dietary AGE intake to increased disc glycation and subsequent mechanical dysfunction. Conclusion: AGEs represent a plausible, modifiable nutritional–metabolic axis linking diet to altered disc biomechanics. While existing data are strongest in cellular and animal models, future human studies integrating dietary assessment, AGE biomarkers, and quantitative mechanical imaging are essential to validate this pathway for clinical risk management.
Azadkiya et al. (2025) studied this question.