Details

Autor(en) / Beteiligte

• García-Prat, Laura
• Martínez-Vicente, Marta
• Perdiguero, Eusebio
• Ortet, Laura
• Rodríguez-Ubreva, Javier
• Rebollo, Elena
• Ruiz-Bonilla, Vanessa
• Gutarra, Susana
• Ballestar, Esteban
• Serrano, Antonio L.
• Sandri, Marco
• Muñoz-Cánoves, Pura

Titel

Autophagy maintains stemness by preventing senescence

Ist Teil von

• Nature (London), 2016-01, Vol.529 (7584), p.37-42

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• The regenerative properties of muscle stem cells decline with age as the stem cells enter an irreversible state of senescence; a study of mouse muscle stem cells reveals that entry into senescence is an autophagy-dependent process and promoting autophagy in old satellite cells can reverse senescence and restore their regenerative properties in an injury model. 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. Stemness maintained by autophagy The regenerative properties of muscle stem cells decline with age, as they enter an irreversible senescence state. Pura Muñoz-Cánoves and colleagues show that before entering senescence, mouse muscle stem cells preserve their repair properties by returning to a reversible quiescence state in an autophagy-dependent manner. Preventing autophagy in young satellite stem cells promotes their entry into senescence and correlates with an increase in mitochondrial dysfunction and oxidative stress. Conversely, promoting autophagy in old satellite cells reverses senescence and restores their regenerative properties in an injury model.