Division of Rheumatology, Allergy, and Immunology, The Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Division of Rheumatology, Allergy, and Immunology, The Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Curr Opin Pharmacol. 2022 Jun;64:102213. doi: 10.1016/j.coph.2022.102213. Epub 2022 Apr 18.
Cellular senescence is associated with normal development and wound healing, but has also been implicated in the pathogenesis of numerous aging-related diseases including osteoarthritis (OA). Treatment strategies for OA are being developed that target senescent cells and the paracrine and autocrine secretions of the senescence-associated secretory phenotype (SASP). The field of potential therapies continues to expand as new mechanistic targets of cell senescence and the SASP are identified. Ongoing pre-clinical and clinical studies of drugs targeting cellular senescence yield significant promise, but have yet to demonstrate long-term efficacy. Therapeutic targeting of senescence is challenged by the diverse phenotypes of senescent cells, which can vary depending on age, species, tissue source, and type of physiologic stressor. Accordingly, there remains considerable demand for more studies to further develop and assess senotherapeutics as disease-modifying treatments for OA.
细胞衰老与正常发育和伤口愈合有关,但也与许多与衰老相关的疾病的发病机制有关,包括骨关节炎 (OA)。目前正在开发针对 OA 的治疗策略,这些策略针对衰老细胞以及衰老相关分泌表型 (SASP) 的旁分泌和自分泌分泌。随着新的细胞衰老和 SASP 的机制靶点的确定,潜在治疗领域继续扩大。针对细胞衰老的药物的持续临床前和临床研究有很大的希望,但尚未证明长期疗效。衰老的治疗靶向受到衰老细胞的不同表型的挑战,这些表型可能因年龄、物种、组织来源和生理应激类型而异。因此,仍然需要更多的研究来进一步开发和评估衰老治疗作为 OA 的疾病修饰治疗。