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The AMPK/p27Kip1 Axis Regulates Autophagy/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells.


ABSTRACT: Skeletal muscle stem cell (MuSC) function declines with age and contributes to impaired muscle regeneration in older individuals. Acting through AMPK/p27Kip1, we have identified a pathway regulating the balance between autophagy, apoptosis, and senescence in aged MuSCs. While p27Kip1 is implicated in MuSC aging, its precise role and molecular mechanism have not been elucidated. Age-related MuSC dysfunction was associated with reduced autophagy, increased apoptosis, and hypophosphorylation of AMPK and its downstream target p27Kip1. AMPK activation or ectopic expression of a phosphomimetic p27Kip1 mutant was sufficient to suppress in vitro apoptosis, increase proliferation, and improve in vivo transplantation efficiency of aged MuSCs. Moreover, activation of the AMPK/p27Kip1 pathway reduced markers of cell senescence in aged cells, which was, in part, dependent on p27Kip1 phosphorylation. Thus, the AMPK/p27Kip1 pathway likely regulates the autophagy/apoptosis balance in aged MuSCs and may be a potential target for improving muscle regeneration in older individuals.

SUBMITTER: White JP 

PROVIDER: S-EPMC6093087 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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The AMPK/p27<sup>Kip1</sup> Axis Regulates Autophagy/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells.

White James P JP   Billin Andrew N AN   Campbell Milton E ME   Russell Alan J AJ   Huffman Kim M KM   Kraus William E WE  

Stem cell reports 20180719 2


Skeletal muscle stem cell (MuSC) function declines with age and contributes to impaired muscle regeneration in older individuals. Acting through AMPK/p27<sup>Kip1</sup>, we have identified a pathway regulating the balance between autophagy, apoptosis, and senescence in aged MuSCs. While p27<sup>Kip1</sup> is implicated in MuSC aging, its precise role and molecular mechanism have not been elucidated. Age-related MuSC dysfunction was associated with reduced autophagy, increased apoptosis, and hypo  ...[more]

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