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Updated: Jul 28, 2025

Single Myofiber Culture Assay for the Assessment of Adult Muscle Stem Cell Functionality Ex Vivo
Published on: February 15, 2021
BTG2 acts as an inducer of muscle stem cell senescence
Baozhou Peng1, Yihan Chen2, Yaning Wang1
1Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; The Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Background:
Muscle aging is associated with muscle stem cell (MuSC) senescence, a process of whose DNA damage accumulation is considered as one of the leading causes. BTG2 had been identified as a mediator of genotoxic and cellular stress signaling pathways, however, its role in senescence of stem cells, including MuSC, remains unknown.
Method:
We first compared MuSCs isolated from young and old mice to evaluate our in vitro model of natural senescence. CCK8 and EdU assays were utilized to assess the proliferation capacity of the MuSCs. Cellular senescence was further assessed at biochemical levels by SA-β-Gal and γHA2.X staining, and at molecular levels by quantifying the expression of senescence-associated genes. Next, by performing genetic analysis, we identified Btg2 as a potential regulator of MuSC senescence, which was experimentally validated by Btg2 overexpression and knockdown in primary MuSCs. Lastly, we extended our research to humans by analyzing the potential links between BTG2 and muscle function decline in aging.
Results:
BTG2 is highly expressed in MuSCs from elder mice showing senescent phenotypes. Overexpression and knockdown of Btg2 stimulates and prevents MuSCs senescence, respectively. In humans, high level of BTG2 is associated with low muscle mass in aging, and is a risk factor of aging-related diseases, such as diabetic retinopathy and HDL cholesterol.
Conclusion:
Our work demonstrates BTG2 as a regulator of MuSC senescence and may serve as an intervention target for muscle aging.
Insights
BTG2 regulates muscle stem cell (MuSC) senescence, a key factor in muscle aging. Targeting BTG2 may offer new strategies to combat age-related muscle decline and associated diseases.
Area of Science:
- Cellular Biology
- Aging Research
- Muscle Stem Cell Biology
Background:
- Muscle aging is linked to muscle stem cell (MuSC) senescence, often caused by DNA damage.
- The role of BTG2, a known stress response mediator, in stem cell senescence, particularly MuSCs, was previously unknown.
Purpose of the Study:
- To investigate the role of BTG2 in MuSC senescence.
- To explore the potential of BTG2 as a therapeutic target for muscle aging.
Main Methods:
- Compared MuSCs from young and old mice to model natural senescence.
- Assessed MuSC proliferation, senescence markers (SA-β-Gal, γH2AX), and gene expression.
- Identified and validated Btg2's regulatory role through overexpression and knockdown experiments in primary MuSCs.
- Analyzed the association between BTG2 and muscle function decline in aging humans.
Main Results:
- BTG2 expression is elevated in senescent MuSCs from older mice.
- Overexpressing Btg2 accelerates MuSC senescence, while its knockdown inhibits senescence.
- In humans, higher BTG2 levels correlate with reduced muscle mass and increased risk of aging-related diseases.
Conclusions:
- BTG2 is identified as a key regulator of muscle stem cell senescence.
- BTG2 represents a potential therapeutic target for interventions aimed at mitigating muscle aging.
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