针对年龄相关肌肉骨骼疾病的衰老疗法：临床前证据的系统综述。
完整摘要 · 中文译文
衰老是骨关节炎、骨质疏松症和肌少症等肌肉骨骼疾病的重要危险因素。细胞衰老通过促进功能改变和促炎环境，导致与年龄相关的组织退化，使衰老治疗药物成为选择性消除衰老细胞或限制其有害效应的有前景的策略。我们的系统综述综合了现有临床前证据，这些证据涉及衰老治疗药物在骨关节炎、骨质疏松症和肌少症小鼠模型中的疗效，分析了结构和功能结局以及参与细胞衰老调节的主要分子机制。按照PRISMA指南在MEDLINE、Scopus和Web of Science数据库中进行了文献检索，同时使用SYRCLE RoB工具评估了纳入研究的方法学质量。共纳入26项实验研究，其中15项涉及骨关节炎模型，6项涉及骨质疏松症模型，5项涉及肌少症模型。总体而言，衰老治疗药物通过减少炎症并通过调节与细胞衰老相关的通路改善所评估的结局，对肌肉骨骼组织表现出保护作用。然而，实验模型、治疗方案和结局指标的异质性限制了得出确定性结论的可能性。仍需进一步研究以阐明所涉及的分子机制、优化治疗策略，并促进实验证据向临床实践的转化。
完整摘要 · 英文原文
Aging is an important risk factor for musculoskeletal disorders such as osteoarthritis, osteoporosis, and sarcopenia. Cellular senescence contributes to age-related tissue deterioration by promoting functional alterations and a pro-inflammatory environment, making senotherapeutics promising strategies to selectively eliminate senescent cells or limit their deleterious effects. Our systematic review synthesized the available preclinical evidence on the efficacy of senotherapeutics in murine models of osteoarthritis, osteoporosis, and sarcopenia, analyzing structural and functional outcomes and the main molecular mechanisms involved in the regulation of cellular senescence. A literature search was conducted in the MEDLINE, Scopus, and Web of Science databases according to PRISMA guidelines, while the methodological quality of the included studies was assessed using the SYRCLE RoB tool. 26 experimental studies were included, of which 15 involved osteoarthritis models, 6 osteoporosis models, and 5 sarcopenic models. Overall, senotherapeutics demonstrated protective effects on musculoskeletal tissues by reducing inflammation and improving the evaluated outcomes through the modulation of pathways associated with cellular senescence. However, the heterogeneity of experimental models, therapeutic protocols, and outcome measures limits the possibility of drawing definitive conclusions. Further studies will be necessary to clarify the molecular mechanisms involved, optimize therapeutic strategies, and promote the translation of experimental evidence into clinical practice.