Abstract: As the core pathological basis of chronic low back pain and spinal dysfunction, the cause of intervertebral disc degeneration (IVDD) has long gone beyond the category of simple mechanical wear, but is a gradual process of deep coupling of mechanical imbalance and biological disorder. The introduction of the concept of "inflammatory aging" provides a new dimension for elucidating its complex evolutionary law. Studies have shown that the pathological evolution of IVDD is not a stacking of isolated events, but a multi-dimensional molecular cascade response driven by inflammatory aging. Internal and external stress triggers the continuous release of the senescence-associated secretory phenotype (SASP) by inducing cells to enter the aging process, which not only reshapes the local immune microenvironment, but also leads to the gradual loss of the original immune privilege of the intervertebral disc. Under the action of chronic low-grade inflammation, cell metabolic reprogramming is becoming more and more significant : excessive lactic acid accumulation forms a feed-forward cycle of "microenvironment acidification-inflammation cascade-matrix degradation" by activating acid-sensitive ion channels. With the progression of the disease, the abnormal activation of the transforming growth factor-β signaling pathway further promotes the phenotypic transformation of cells, resulting in the transformation of the elastic matrix to pathological fibrosis, which eventually leads to the loss of spinal motor unit function. In view of the above pathological processes, this paper systematically reviews the cutting-edge intervention strategies to block the cascade reaction, including the use of senolytic drugs to target the removal of senescent cells to block the source of inflammation, the targeting of the inhibition of SASP paracrine effects "with the help of functional carriers, and the reshaping of matrix homeostasis with the help of responsive hydrogels. In-depth analysis of the molecular cascade mechanism triggered by inflammatory aging and synergistic biomaterial technology to block the pathological circulation can provide important theoretical support for early intervention and tissue regeneration and repair of IVDD.

Key words: Intervertebral disc degeneration, Inflammaging, Cellular senescence, Acid-sensing ion channels, TGF-β signaling pathway, Pathological fibrosis, Functionalized biomaterials

摘要： 作为慢性腰腿痛及脊柱功能障碍的核心病理基础，椎间盘退变（IVDD）的成因早已超越单纯的力学磨损范畴，而是力学失衡与生物学紊乱深度耦合的渐变过程。“炎性衰老”概念的引入为阐明其复杂的演进规律提供了新维度。研究表明，IVDD的病理演变不是孤立事件的堆砌，而是一个由炎性衰老驱动的多维分子级联响应。内外源性应力通过诱导细胞步入衰老程序，触发衰老相关分泌表型（SASP）的持续释放，这不仅重塑了局部免疫微环境，还导致椎间盘原本的免疫特权逐渐丧失。在慢性低度炎症的作用下，细胞代谢重编程日趋显著：过量乳酸堆积通过激活酸敏感离子通道，形成了“微环境酸化-炎症级联-基质降解”的前馈循环。随着病变进展，转化生长因子-β信号通路异常活化进一步推动细胞表型转换，造成弹性基质向病理性纤维化转变，最终导致脊柱运动单元功能丧失。针对以上病理过程，本文系统综述了阻断该级联反应的前沿干预策略，包括利用衰老细胞清除剂药物靶向清除衰老细胞以阻断炎症源头，到借助功能化载体靶向抑制SASP旁分泌效应，再到借助响应性水凝胶重塑基质稳态。深入解析了炎性衰老触发的分子级联机制，并协同生物材料技术阻断病理循环，可以为IVDD的早期干预与组织再生修复提供重要理论支撑。

关键词: 椎间盘退行性变, 炎性衰老, 细胞衰老, 酸敏感离子通道, TGF-β 信号通路, 病理性纤维化, 功能化生物材料