Autophagy maintains stemness by preventing senescence
| العنوان: | Autophagy maintains stemness by preventing senescence |
|---|---|
| المؤلفون: | Ruiz-Bonilla, Susana Gutarra, Marta Martinez-Vicente, Javier Rodríguez-Ubreva, Pura Muñoz-Cánoves, Laura García-Prat, Esteban Ballestar, Eusebio Perdiguero, Antonio L. Serrano, Marco Sandri, Laura Ortet, Elena Rebollo |
| المساهمون: | Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), European Commission, Instituto de Salud Carlos III, Fundació La Marató de TV3, Ministerio de Economía y Competitividad (España), Fondation Leducq |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Senescence, Aging, Sarcopenia, Satellite Cells, Skeletal Muscle, Cell Count, Biology, Epigenesis, Genetic, Mice, 03 medical and health sciences, 0302 clinical medicine, Mitophagy, Autophagy, medicine, Animals, Homeostasis, Humans, Regeneration, senescence, autophagy, stem cells, Muscle, Skeletal, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, 030304 developmental biology, Organelles, 0303 health sciences, Multidisciplinary, Proteins, medicine.disease, Mitochondria, Cell biology, Oxidative Stress, 030104 developmental biology, Proteostasis, Ageing, 030220 oncology & carcinogenesis, Stem cell, Reactive Oxygen Species, Cell aging |
| الوصف: | Laura García-Prat et al. 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. The authors acknowledge funding from MINECO, Spain (SAF2012-38547, SAF2015-67369-R, PLE2009-0124; SAF2009-08374; “María de Maeztu” Programme for Units of Excellence in R&D MDM-2014-0370), AFM, E-Rare/ERANET, Fundació Marató TV3, MDA, EU-FP7 (Myoage, Optistem and Endostem) and DuchennePP-NL. M.M.-V. acknowledges funding from ISCIII, Spain (FIS-PS09/01267, FIS-PI13/02512, CP09/00184, PI14/01529) and CIBERNED; and MS from the European Union ERC (282310-MyoPHAGY) and Foundation Leducq. L.G.-P. was supported by a Predoctoral Fellowship from Programa de Formación de Personal Investigador (Spain) |
| تدمد: | 1476-4687 0028-0836 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bb2aef883e8dde32b63cc52a0f897ccTest https://doi.org/10.1038/nature19415Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3bb2aef883e8dde32b63cc52a0f897cc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764687 00280836 |
|---|