Abstract:
Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration. The mode of action of these senotherapeutics, as well as the challenges in their practical application, will also be explicitly discussed in an attempt to direct their more targeted and effective use in exclusive or combinatorial therapeutic schemes for the prevention and/or treatment of disc degenerative disorders.
摘要:
慢性腰痛,残疾的主要原因,具有巨大的全球社会经济影响,与椎间盘退变密不可分。另一方面,在老化和退变的椎间盘中发现衰老细胞数量增加,它们的衰老相关分泌表型(SASP)与细胞外基质的定性/定量改变有关,并最终与组织稳态的紊乱有关.鉴于选择性消除衰老细胞(通过所谓的senolytics)或将其分泌组修改为较少分解代谢/炎症表型(通过称为senomorphics的分子)已被报道可以减轻几种与年龄相关的疾病的症状并改善衰老期间的组织质量。在这里,我们将回顾从植物和天然产物中提取的衰老和衰老因子对椎间盘退变的作用。这些感官疗法的作用方式,以及它们在实际应用中的挑战,还将明确讨论,试图将它们更有针对性和有效地用于预防和/或治疗椎间盘退行性疾病的排他性或组合治疗方案。