Scholarlink

<p>Proteostasis supports stemness, and its loss correlates with the functional decline of diverse stem cell types. Chaperone-mediated autophagy (CMA) is a selective autophagy pathway implicated in proteostasis, but whether it plays a role in muscle stem cell (MuSC) function is unclear. Here we show that CMA is necessary for MuSC regenerative capacity throughout life. Genetic loss of CMA in young MuSCs, or failure of CMA in aged MuSCs, causes proliferative impairment resulting in defective skeletal muscle regeneration. Using comparative proteomics to identify CMA substrates, we find that actin cytoskeleton organization and glycolytic metabolism are key processes altered in aged murine and human MuSCs. CMA reactivation and glycolysis enhancement restore the proliferative capacity of aged mouse and human MuSCs, and improve their regenerative ability. Overall, our results show that CMA is a decisive stem cell-fate regulator, with implications in fostering muscle regeneration in old age.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Chaperone-mediated autophagy sustains muscle stem cell regenerative functions but declines with age

  • 期刊论文

  • 发表日期：

    2025年12月3日

查看全文
  • Ignacio Ramírez-Pardo,
  • Silvia Campanario,
  • Bhakti Chavda,
  • Olaya Santiago-Fernández,
  • Marta Flández,
  • Mercedes Grima-Terrén,
  • Andrés Cisneros,
  • Aina Calls-Cobos,
  • Daniel N. Itzhak,
  • Bryan Ngo,
  • Sudha Janaki-Raman,
  • Edward D. Kantz,
  • Laura Ortet,
  • Antonio Diaz,
  • Kristen Lindenau,
  • Julio Doménech-Fernández,
  • Mari Carmen Gómez-Cabrera,
  • Emilio Camafeita,
  • Jesús Vázquez,
  • Marta Martinez-Vicente,
  • Antonio L. Serrano,
  • Eusebio Perdiguero,
  • Joan Isern,
  • Ana Maria Cuervo,
  • Pura Muñoz-Cánoves

摘要

Proteostasis supports stemness, and its loss correlates with the functional decline of diverse stem cell types. Chaperone-mediated autophagy (CMA) is a selective autophagy pathway implicated in proteostasis, but whether it plays a role in muscle stem cell (MuSC) function is unclear. Here we show that CMA is necessary for MuSC regenerative capacity throughout life. Genetic loss of CMA in young MuSCs, or failure of CMA in aged MuSCs, causes proliferative impairment resulting in defective skeletal muscle regeneration. Using comparative proteomics to identify CMA substrates, we find that actin cytoskeleton organization and glycolytic metabolism are key processes altered in aged murine and human MuSCs. CMA reactivation and glycolysis enhancement restore the proliferative capacity of aged mouse and human MuSCs, and improve their regenerative ability. Overall, our results show that CMA is a decisive stem cell-fate regulator, with implications in fostering muscle regeneration in old age.