title: Autophagy maintains stemness by preventing senescence.
abstract: During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: García-Prat
authors.affiliation: Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-CIBERNED, E-08035 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Vicente
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Perdiguero
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ortet
authors.affiliation: Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, E-08907 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Ubreva
authors.affiliation: Advanced Fluorescence Microscopy Unit, Molecular Biology Institute of Barcelona (IBMB-CSIC), E-08028 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Rebollo
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ruiz-Bonilla
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Gutarra
authors.affiliation: Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, E-08907 Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Serrano
authors.affiliation: Department of Biomedical Science, University of Padova, 35100 Padova, Italy.|Telethon Institute of Genetics and Medicine (TIGEM), 80131 Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain.|ICREA, E-08908 Barcelona, Spain.
authors.forename: Pura
authors.initials: P
authors.lastname: Muñoz-Cánoves
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002452:Cell Count; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D044127:Epigenesis, Genetic; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D015388:Organelles / Q000378:metabolism; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration; D055948:Sarcopenia / Q000473:pathology / Q000517:prevention & control; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000473:pathology
chemical_list: C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011506:Proteins; D017382:Reactive Oxygen Species