Ameliorating the hallmarks of cellular senescence in skeletal muscle myogenic progenitors in vitro and in vivo.
Ameliorating the hallmarks of cellular senescence in skeletal muscle myogenic progenitors in vitro and in vivo.
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DOI：
10.1126/sciadv.abe5671
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发表时间：
2021-09-03
期刊：
影响因子：
13.6
通讯作者：
Andreadis ST
中科院分区：
文献类型：
--
作者：
Shahini A;Rajabian N;Choudhury D;Shahini S;Vydiam K;Nguyen T;Kulczyk J;Santarelli T;Ikhapoh I;Zhang Y;Wang J;Liu S;Stablewski A;Thiyagarajan R;Seldeen K;Troen BR;Peirick J;Lei P;Andreadis ST
The embryonic factor NANOG reverses aging hallmarks and rejuvenates senescent skeletal muscle progenitors. Senescence of myogenic progenitors impedes skeletal muscle regeneration. Here, we show that overexpression of the transcription factor NANOG in senescent myoblasts can overcome the effects of cellular senescence and confer a youthful phenotype to senescent cells. NANOG ameliorated primary hallmarks of cellular senescence including genomic instability, loss of proteostasis, and mitochondrial dysfunction. The rejuvenating effects of NANOG included restoration of DNA damage response via up-regulation of DNA repair proteins, recovery of heterochromatin marks via up-regulation of histones, and reactivation of autophagy and mitochondrial energetics via up-regulation of AMP-activated protein kinase (AMPK). Expression of NANOG in the skeletal muscle of a mouse model of premature aging restored the number of myogenic progenitors and induced formation of eMyHC+ myofibers. This work demonstrates the feasibility of reversing the effects of cellular senescence in vitro and in vivo, with no need for reprogramming to the pluripotent state.
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