Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju-si 63243, Republic of Korea.
Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju-si 63243, Republic of Korea; Department of Biotechnology, School of Bio, Chemical and Processing Engineering (SBCE), Kalasalingam Academy of Research and Education, Krishnankoil 626126, India.
Ageing Res Rev. 2024 Apr;96:102275. doi: 10.1016/j.arr.2024.102275. Epub 2024 Mar 15.
Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA. Apoptosis resistance; irreversible cell cycle arrest; increased p16INK4a expression, secretion of senescence-associated secretory phenotype factors, senescence-associated β-galactosidase levels, secretion of extracellular vesicles, and levels of reactive oxygen and reactive nitrogen species; and mitochondrial dysregulation are some common changes in cellular senescence in joint tissues. Development of OA correlates with an increase in the density of SCs in joint tissues. Senescence-associated secretory phenotype has been linked to OA and cartilage breakdown. Senolytics and therapeutic pharmaceuticals are being focused upon for OA management. SCs can be selectively eliminated or killed by senolytics to halt the pathogenesis and progression of OA. Comprehensive understanding of how aging affects joint dysfunction will benefit OA patients. Here, we discuss age-related mechanisms associated with OA pathogenesis and senolytics as an emerging modality in the management of age-related SCs and pathogenesis of OA in preclinical and clinical studies.
骨关节炎（OA）是一种影响 65 岁以上数百万人的慢性关节疾病，是老年人关节活动度下降的主要肌肉骨骼原因。其特征为持续疼痛和关节软骨的逐渐恶化。关节中衰老和衰老细胞（SCs）的积累常与 OA 相关。细胞衰老时常见的改变包括：细胞凋亡抵抗；不可逆的细胞周期停滞；p16INK4a 表达增加、衰老相关分泌表型因子分泌、衰老相关β-半乳糖苷酶水平、细胞外囊泡分泌以及活性氧和活性氮物种水平增加；和线粒体失调。OA 的发展与关节组织中 SCs 密度的增加相关。衰老相关分泌表型与 OA 和软骨分解有关。衰老细胞清除剂和治疗性药物正被用于 OA 的管理。衰老细胞清除剂可以选择性地消除或杀死 SCs，从而阻止 OA 的发病机制和进展。全面了解衰老如何影响关节功能将使 OA 患者受益。在这里，我们讨论了与 OA 发病机制相关的与年龄相关的机制以及衰老细胞清除剂作为一种新兴的治疗方法，用于治疗与年龄相关的 SCs 和 OA 的发病机制的临床前和临床研究。
