Autophagy maintains stemness by preventing senescence

Laura García-Prat, Marta Martínez-Vicente, Eusebio Perdiguero, Laura Ortet, Javier Rodríguez-Ubreva, Elena Rebollo, Vanessa Ruiz-Bonilla, Susana Gutarra, Esteban Ballestar, Antonio L. Serrano, Marco Sandri and Pura Muñoz-Cánoves
Additional contact information
Marta Martínez-Vicente: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Eusebio Perdiguero: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Laura Ortet: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Javier Rodríguez-Ubreva: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Elena Rebollo: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Vanessa Ruiz-Bonilla: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Susana Gutarra: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Esteban Ballestar: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Antonio L. Serrano: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Marco Sandri: Cell Biology Group, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), E-08003 Barcelona, Spain. Present address: Tissue Regeneration Laboratory, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.

Nature, 2016, vol. 534, issue 7607, S3-S4

Abstract: 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.

Date: 2016
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DOI: 10.1038/nature19415

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