年轻小鼠纤维脂肪祖细胞通过旁分泌作用改善肌肉干细胞的衰老

doi:10.16352/j.issn.1001-6325.2026.06.0747

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (6): 747-754.doi: 10.16352/j.issn.1001-6325.2026.06.0747

年轻小鼠纤维脂肪祖细胞通过旁分泌作用改善肌肉干细胞的衰老

朱星雨¹, 肖雨桢¹, 陈运华¹, 孙若曦¹, 孙昭², 韩钦^1*, 赵春华^1*

1.中国医学科学院北京协和医学院基础医学研究所人工智能细胞医药工程技术交叉创新与临床转化北京市重点实验室, 北京 100005;
2.中国医学科学院北京协和医学院北京协和医院肿瘤内科,北京 100730

收稿日期:2026-03-06 修回日期:2026-03-27 出版日期:2026-06-05 发布日期:2026-05-27
通讯作者: ^*hanqin@ibms.pumc.edu.cn;zhaochunhua@ibms.pumc.edu.cn
基金资助:
国家自然科学基金(82471598)

Fibro-adipogenic progenitors from young mice alleviate senescence of muscle stem cells via paracrine regulation

ZHU Xingyu¹, XIAO Yuzhen¹, CHEN Yunhua¹, SUN Ruoxi¹, SUN Zhao², HAN Qin^1*, ZHAO Chunhua^1*

1. Beijing Key Laboratory of Artificial Intelligence and Cell-based Medical Engineering for Interdisciplinary Innovation and Clinical Translation, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005;
2. Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Received:2026-03-06 Revised:2026-03-27 Online:2026-06-05 Published:2026-05-27
Contact: ^*hanqin@ibms.pumc.edu.cn;zhaochunhua@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探讨纤维脂肪祖细胞(FAPs)年龄相关变化对肌肉干细胞(MuSCs)衰老的影响。方法分离年轻和衰老小鼠骨骼肌来源的MuSCs和FAPs,比较年轻与衰老FAPs的增殖能力、成纤维分化能力及相关基因表达水平。建立D-半乳糖(D-gal)诱导的C2C12细胞衰老模型和MuSCs复制性衰老模型,采用年轻FAPs条件培养基进行干预,通过EdU、SA-β-gal染色及qPCR检测MuSCs的增殖及衰老水平。进一步利用不同来源FAPs条件培养基处理原代MuSCs,评价FAPs年龄对MuSCs功能的影响。结果与年轻FAPs相比,衰老小鼠来源FAPs的增殖能力显著降低,成纤维分化能力增强,且p21表升高而IGF1表达降低。年轻FAP条件培养基可显著降低D-gal诱导的C2C12细胞衰老水平,并在复制性衰老MuSCs中降低SA-β-gal阳性率及p21表达,同时恢复细胞增殖能力。此外,年轻FAP条件培养基可显著改善衰老小鼠来源MuSCs的衰老表型,而衰老FAP条件培养基未见明显作用。结论衰老可显著改变FAPs的功能状态,而年轻FAPs分泌的因子能够在一定程度上恢复衰老MuSCs的增殖能力并降低其衰老水平,提示FAPs年龄相关变化是调控肌肉干细胞衰老的重要微环境因素。

关键词: 肌少症, 肌肉干细胞, 成纤维/脂肪祖细胞

Abstract: Objective To investigate the effects of age-related changes in fibro-adipogenic progenitors (FAPs) on the senescence of muscle stem cells (MuSCs). Methods MuSCs and FAPs were isolated from skeletal muscle of young and aged mice. The proliferative capacity, fibrogenic differentiation potential, and expression of related genes were compared between FAPs from young and aged mice. A D-galactose-induced senescence model in C2C12 cells and a replicative senescence model in MuSCs were established. The conditioned medium of young mice-derived FAPs was used for intervention of the model cells, and the proliferation and senescence of MuSCs were evaluated by EdU incorporation, senescence-associated β-galactosidase (SA-β-gal) staining, and qPCR. In addition, conditioned media of FAPs from mice of different ages were used to treat primary MuSCs to evaluate the effect of the age of FAPs on the function of MuSCs. Results Compared with the FAPs from young mice, the FAPs from aged mice exhibited significantly reduced proliferative capacity and enhanced fibrogenic differentiation, accompanied by increased expression of p21 and decreased expression of IGF1. The conditioned medium of FAPs from young mice markedly alleviated D-galactose-induced senescence in C2C12 cells. In the MuSC model of replicative senescence, treatment with the conditioned medium of FAPs from young mice decreased the proportion of SA-β-gal-positive cells and reduced p21 expression while restoring proliferative capacity. Furthermore, the conditioned medium of FAPs from young mice significantly ameliorated the senescent phenotype of MuSCs isolated from aged mice, whereas the conditioned medium of FAPs from aged mice showed no obvious effect. Conclusions Aging significantly alters the functional state of FAPs. Factors secreted by FAPs from young mice can partially restore the proliferative capacity of aged MuSCs and reduce their senescence level, which suggests that age-related alterations in FAPs represent a key microenvironmental factor regulating the senescence of muscle stem cells.

Key words: sarcopenia, muscle stem cells, fibro-adipogenic progenitors

中图分类号:

朱星雨, 肖雨桢, 陈运华, 孙若曦, 孙昭, 韩钦, 赵春华. 年轻小鼠纤维脂肪祖细胞通过旁分泌作用改善肌肉干细胞的衰老[J]. 基础医学与临床, 2026, 46(6): 747-754.

ZHU Xingyu. Fibro-adipogenic progenitors from young mice alleviate senescence of muscle stem cells via paracrine regulation[J]. Basic & Clinical Medicine, 2026, 46(6): 747-754.

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年轻小鼠纤维脂肪祖细胞通过旁分泌作用改善肌肉干细胞的衰老

Fibro-adipogenic progenitors from young mice alleviate senescence of muscle stem cells via paracrine regulation

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