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.

Abstract

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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