Metabolic reprogramming in intervertebral disc degeneration: mechanisms and therapeutic opportunities

Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and disability and imposes a substantial socioeconomic burden. Increasing evidence indicates that metabolic reprogramming is closely involved in the initiation and progression of IVDD. In this review, we summarize the major pathological processes associated with IVDD, including apoptosis, autophagy dysregulation, oxidative stress, inflammatory responses, and extracellular matrix (ECM) degradation. We further discuss alterations in glucose, lipid, and amino acid metabolism, with particular emphasis on the contribution of mitochondrial dysfunction to metabolic imbalance in disc cells. In addition, we outline the genetic, environmental, and signaling factors that regulate metabolic reprogramming, including pathways such as mTOR and AMPK. Finally, we review emerging metabolism-related therapeutic strategies, including metabolic enzyme modulation, antioxidants, and mitochondrial protectors. Collectively, current evidence suggests that metabolic reprogramming is an important component of IVDD pathogenesis and may provide a useful framework for the development of targeted therapeutic approaches.