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Publication : Autophagy maintains stemness by preventing senescence.

First Author  García-Prat L Year  2016
Journal  Nature Volume  529
Issue  7584 Pages  37-42
PubMed ID  26738589 Mgi Jnum  J:228495
Mgi Id  MGI:5707520 Doi  10.1038/nature16187
Citation  Garcia-Prat L, et al. (2016) Autophagy maintains stemness by preventing senescence. Nature 529(7584):37-42
abstractText  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.
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