Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments

IF 6.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-07-18 DOI:10.1002/ctm2.70417

Zhengdong Zhang, Pan Liu, Yu Song, Liang Ma, Yan Xu, Jie Lei, Bide Tong, Dingchao Zhu, Huaizhen Liang, Hongchuan Wang, Xingyu Zhou, Zixuan Ou, Junyu Wei, Hanpeng Xu, Di Wu, Shuchang Peng, Yifan Du, Zhi Du, Bingjin Wang, Zhiwei Liao, Wencan Ke, Kangcheng Zhao, Xiqin Xia, Lei Tan, Xiaobo Feng, Gang Liu, Shuai Li, Kun Wang, Cao Yang

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Abstract

Background

Osteoblast senescence is a central driverof age-related osteoporosis. Accumulating evidence shows that counteractingthis senescence can substantially mitigate bone loss. In this review, we summarize the hallmarks of osteoblast senescence, the signaling pathways involved, and therapeutic strategies that target osteoblast senescence tocombat age-related osteoporosis.

Methods

Chronic diseases associated with ageingpose a significant threat to human health. Studies have shown that osteoporosisis closely linked to the ageing process of the body and the senescence ofosteoblasts within the bone microenvironment. Counteracting the senescence ofosteoblasts and maintaining the balance of differentiation, proliferation andfunction between osteoclasts and osteoblasts has been a key focus in the research of age-related osteoporosis and bone loss. The biological behaviour andfunctionality of the osteoblast lineage related to senescence are modulated bya variety of targets, including signalling pathways, proteins and genes associated with ageing. This review aims to discuss the senescence-related characteristics of the osteoblast lineage, dissect the interplay and mechanisms between it and ageing-associated signalling pathways, proteinsand genes, as well as current strategies for the prevention and treatment ofosteoblast senescence.

Conclusion

This review systematically examines the regulatory interactions among markers, therapeutic targets, and signalingpathways associated with osteoblast senescence, alongside current potential strategies for targeting this process. It provides more comprehensive information for future research into the complex mechanisms underlying age-related osteoporosis driven by osteoblast senescence.

Key points

Osteoblast senescence is a key driver of age-related osteoporosis, disrupting bone formation and homeostasis.
Aging impacts osteoblasts through multiple pathways, including telomere shortening, genomic instability, SASP secretion, and others.
Bone loss related to osteoblast senescence involves the activation and crosstalk of multiple signaling pathways.
The options for combating and treating osteoblast senescence toachieve anti-osteoporosis are numerous, but still challenging.

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解决成骨细胞衰老：分子途径和抗衰老治疗的前沿

背景成骨细胞衰老是年龄相关性骨质疏松症的主要驱动因素。越来越多的证据表明，对抗这种衰老可以大大减轻骨质流失。在这篇综述中，我们总结了成骨细胞衰老的特征，所涉及的信号通路，以及针对成骨细胞衰老对抗年龄相关性骨质疏松症的治疗策略。方法与衰老相关的慢性疾病对人类健康构成重大威胁。研究表明，骨质疏松症的发生与机体的衰老过程和骨微环境中成骨细胞的衰老密切相关。对抗成骨细胞的衰老，维持破骨细胞与成骨细胞分化、增殖和功能的平衡一直是老年性骨质疏松和骨质流失研究的重点。与衰老相关的成骨细胞谱系的生物学行为和功能受到多种靶点的调节，包括与衰老相关的信号通路、蛋白质和基因。本文旨在讨论成骨细胞谱系的衰老相关特征，剖析其与衰老相关信号通路、蛋白质和基因之间的相互作用和机制，以及目前预防和治疗成骨细胞衰老的策略。本综述系统地探讨了与成骨细胞衰老相关的标志物、治疗靶点和信号通路之间的调节相互作用，以及目前针对这一过程的潜在策略。它为未来研究成骨细胞衰老驱动的年龄相关性骨质疏松症的复杂机制提供了更全面的信息。成骨细胞衰老是年龄相关性骨质疏松症的关键驱动因素，破坏骨形成和体内平衡。衰老通过多种途径影响成骨细胞，包括端粒缩短、基因组不稳定、SASP分泌等。与成骨细胞衰老相关的骨质流失涉及多种信号通路的激活和串扰。对抗和治疗成骨细胞衰老以达到抗骨质疏松症的选择很多，但仍然具有挑战性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.