2026-07-26T08:12:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/276032026-07-17T00:17:56Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Ramírez-Pardo, Ignacio author Campanario, Silvia author Chavda, Bhakti author Santiago-Fernández, Olaya author Flández, Marta author Grima-Terrén, Mercedes author Cisneros, Andrés author Calls-Cobos, Aina author Itzhak, Daniel N author Ngo, Bryan author Janaki-Raman, Sudha author Kantz, Edward D author Ortet, Laura author Diaz, Antonio author Lindenau, Kristen author Doménech-Fernández, Julio author Gómez-Cabrera, Mari Carmen author Camafeita, Emilio author Vázquez, Jesús author Martinez-Vicente, Marta author Serrano, Antonio L author Perdiguero, Eusebio author Isern, Joan author Cuervo, Ana Maria author Muñoz-Cánoves, Pura author 2025-12 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. Nat Metab. 2025 Dec;7(12):2571-2588. NATURE METABOLISM 41339968 https://hdl.handle.net/20.500.12105/27603 Chaperone-mediated autophagy sustains muscle stem cell regenerative functions but declines with age.