Xiong Jinming, Guo Qiaoyue, Luo Xianghang
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China.
Front Med. 2025 May 2. doi: 10.1007/s11684-025-1125-7.
Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
衰老通常与肌肉骨骼功能下降相关,导致活动能力降低和虚弱加剧。作为衰老的一个标志,细胞衰老在各种与年龄相关的肌肉骨骼疾病中起着关键作用,包括骨质疏松症、骨关节炎、椎间盘退变和肌肉减少症。衰老的有害影响主要归因于干细胞再生能力受损以及衰老细胞积累所产生的促炎环境。分泌的衰老相关分泌表型(SASP)可诱导邻近细胞衰老,进一步放大衰老信号。尽管在小鼠模型中,清除衰老细胞和抑制SASP因子已显示出缓解疾病进展和恢复肌肉骨骼健康的前景,但临床试验尚未证明有显著疗效。本综述总结了细胞衰老在与年龄相关的肌肉骨骼疾病中的机制,并讨论了针对细胞衰老的潜在治疗策略。
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