细胞生物学
同源盒蛋白纳米
生物
骨骼肌
衰老
重编程
心肌细胞
DNA损伤
肌生成素
蛋白质稳态
MyoD公司
祖细胞
DNA修复
早熟
肌发生
基因组不稳定性
诱导多能干细胞
干细胞
胚胎干细胞
遗传学
细胞
解剖
DNA
基因
作者
Aref Shahini,Nika Rajabian,Debanik Choudhury,Shahryar Shahini,Kalyan Vydiam,T M Nguyen,Joseph Kulczyk,Tyler Santarelli,Izuagie Ikhapoh,Yali Zhang,Jianmin Wang,Song Liu,Aimee Stablewski,Ramkumar Thiyagarajan,Kenneth L. Seldeen,Bruce R. Troen,Jennifer Peirick,Pedro Lei,Stelios T. Andreadis
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-09-03
卷期号:7 (36)
被引量:17
标识
DOI:10.1126/sciadv.abe5671
摘要
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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