2026-07-26T08:12:56Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/276032026-07-17T00:17:56Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
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
2026-07-16T12:20:23Z
2026-07-16T12:20:23Z
2025-12
Nat Metab. 2025 Dec;7(12):2571-2588.
NATURE METABOLISM
41339968
https://hdl.handle.net/20.500.12105/27603
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.
eng
Chaperone-mediated autophagy sustains muscle stem cell regenerative functions but declines with age.
research article
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URL
https://repisalud.isciii.es/bitstreams/42d209d9-05b7-47c9-87ad-c6b6dae21af3/download
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45e76e18453578233a991a6d6dfd6cac
257866
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Chaperone_mediated autophagy sustains_Nat Metab_2025.pdf