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与年龄相关的肌肉骨骼疾病中的细胞衰老

Cellular senescence in age-related musculoskeletal diseases.

作者信息

Xiong Jinming, Guo Qiaoyue, Luo Xianghang

机构信息

Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China.

出版信息

Front Med. 2025 May 2. doi: 10.1007/s11684-025-1125-7.


DOI:10.1007/s11684-025-1125-7
PMID:40314896
Abstract

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.

摘要

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。

相似文献

[1]
Cellular senescence in age-related musculoskeletal diseases.

Front Med. 2025-5-2

[2]
Mitochondria and cellular senescence: Implications for musculoskeletal ageing.

Free Radic Biol Med. 2018-10-15

[3]
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Ageing Res Rev. 2025-7

[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration.

Free Radic Biol Med. 2024-11-1

[2]
PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging.

Bone Res. 2024-7-4

[3]
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Nat Med. 2024-9

[4]
ROS-mediated cytoplasmic localization of CARM1 induces mitochondrial fission through DRP1 methylation.

Redox Biol. 2024-7

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M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis.

J Nanobiotechnology. 2024-5-31

[6]
Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3.

Bone Res. 2024-5-24

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Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure.

Int J Oral Sci. 2024-5-22

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Semin Cancer Biol. 2024-6

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Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair.

J Clin Invest. 2024-5-16

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The senescence-associated secretory phenotype and its physiological and pathological implications.

Nat Rev Mol Cell Biol. 2024-12

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