Nanog protein reverses signs of aging in new study in Science Advances from scientists at the University at Buffalo

Posted by Wendy Wise on

Scientists from the University of New York at Buffalo published a study in Science Advances that supports that overexpression of the transcription factor NANOG can reverse the signs of cellular aging in muscles without having to revert the cells to a stem-cell like state. The work could help lead to new treatments or therapies that help reverse cellular senescence, and aid the many people suffering from age-related disorders.

Read the study in Science Advances

Ameliorating the hallmarks of cellular senescence in skeletal muscle myogenic progenitors in vitro and in vivo

Aref Shahini, Nika Rajabian, Debanik Choudhury, Shahryar Shahini, Kalyan Vydiam, Thy Nguyen, Joseph Kulczyk, Tyler Santarelli, Izuagie Ikhapoh, Yali Zhang, Jianmin Wang, Song Liu, Aimee Stablewski, Ramkumar Thiyagarajan, Kenneth Seldeen, Bruce R. Troen, Jennifer Peirick, Pedro Leiand, Stelios T. Andreadis

September 3, 2022

Science Advances

Abstract:

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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