Inflammation, Fibrosis, and Matrix Remodeling in Age-Related Intervertebral Disc Pathologies

Age-related intervertebral disc (IVD) pathologies are a major driver of chronic low back pain and disability. Long framed as “wear and tear,” disc degeneration is now recognized as an active, cell-mediated process shaped by persistent low-grade inflammation, maladaptive fibrosis, and dysregulated extracellular matrix (ECM) remodeling. These intertwined mechanisms alter disc composition and biomechanics, impair nutrient transport, promote neurovascular ingrowth, and amplify nociceptive signaling—yet we still lack a unified view of how they arise with aging, why progression varies across individuals, and which pathways offer the most tractable therapeutic targets.This Research Topic will gather cutting-edge mechanistic and translational studies that clarify how inflammatory signaling, fibrotic programs, and matrix remodeling cooperate to drive disc dysfunction across the lifespan. We welcome work examining interactions among nucleus pulposus, annulus fibrosus, and cartilage endplate cells; immune activation and infiltration; senescence and the senescence-associated secretory phenotype (SASP); and age-linked stressors such as oxidative damage, metabolic dysregulation, and altered mechanobiology. Particular interest includes studies defining how cytokines and innate immune pathways (e.g., IL-1β, TNF-α, IL-6, chemokines, inflammasome signaling) influence ECM turnover and repair through proteases and remodeling enzymes (e.g., MMPs, ADAMTS, LOX/LOXL), shifting collagen–proteoglycan balance, hydration, and structural integrity.We encourage submissions that connect molecular and cellular remodeling to functional outcomes, including mechanical failure, endplate–disc cross-talk, vertebral changes, and clinically relevant pain phenotypes. Multi-omics (single-cell, spatial transcriptomics/proteomics), advanced imaging, quantitative histopathology, computational modeling, and biomechanical testing are especially welcome, as are human tissue studies and cross-species work that improves the translational relevance of aging models.A central goal is to spotlight actionable biology. We invite papers on therapeutic strategies that modulate inflammatory–fibrotic remodeling rather than symptoms alone, including senolytics/senomorphics, pro-resolving mediators, targeted anti-cytokine approaches, anti-fibrotic signaling modulation (e.g., TGF-β axis), ECM-directed biomaterials, gene/RNA-based interventions, regenerative cell therapies, and mechanobiology-informed rehabilitation. Studies proposing robust biomarkers—molecular, imaging, or circulating—linked to remodeling states and treatment response are highly encouraged.By integrating inflammation, fibrosis, and matrix remodeling into a coherent framework, this collection aims to accelerate discovery of predictive markers and mechanism-based interventions to preserve disc function and reduce age-related spine pain. Topic editors: Graciosa Q Teixeira Source: https://www.frontiersin.org/research-topics/76873/inflammation-fibrosis-and-matrix-remodeling-in-age-related-intervertebral-disc-pathologies