Reversibility of cellular aging by reprogramming through an embryonic-like state: a new paradigm for human cell rejuvenation


 

 

New articles in this journal are licensed under a Creative Commons Attribution 3.0 United States License. 

 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

 

 

 

 

 

 
 

 

 

 

Reversibility of cellular aging by 

reprogramming through an 

embryonic-like state: a new 

paradigm for human cell 

rejuvenation 

 

Jean-Marc Lemaitre 

 
Director of INSERM Laboratory, Genome 
Plasticity and Aging, Institute of 
Functional Genomics, Montpellier, France

 

Vol. 2, Suppl. (2013)   |   ISSN 2166-7403 (online)    

DOI 10.5195/cajgh.2013.88   |   http://cajgh.pitt.edu 

http://www.library.pitt.edu/
http://www.pitt.edu/
http://www.library.pitt.edu/articles/digpubtype/index.html
http://www.upress.pitt.edu/upressIndex.aspx
http://creativecommons.org/licenses/by/3.0/us/


 

 

LEMAITRE 

 

 

This work is licensed under a Creative Commons Attribution 3.0 United States License. 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, Suppl. (2013)  |  ISSN 2166-7403 (online)  |  DOI 10.5195/cajgh.2013.88  |  http://cajgh.pitt.edu 

  

 

Abstract 

Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive 

patient-specific stem cells with potential application in autologous tissue replacement therapies and without the ethical concerns 

of Embryonic Stem Cells (hESC). However, this strategy still suffers from several hurdles that need to be overcome before 

clinical applications. Among them, cellular senescence, which contributes to aging and restricted longevity, has been described as 

a barrier to the derivation of iPSCs. This suggests that aging might be an important limitation for therapeutic purposes for elderly 

individuals. Senescence is characterized by an irreversible cell cycle arrest in response to various forms of stress, including 

activation of oncogenes, shortened telomeres, DNA damage, oxidative stress, and mitochondrial dysfunction. To overcome this 

barrier, we developed an optimized 6-factor-based reprogramming protocol that is able to cause efficient reversing of cellular 

senescence and reprogramming into iPSCs. We demonstrated that iPSCs derived from senescent and centenarian fibroblasts have 

reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from 

hESC. Finally, we demonstrate that re-differentiation led to rejuvenated cells with a reset cellular physiology, defining a new 

paradigm for human cell rejuvenation. We discuss the molecular mechanisms involved in cell reprogramming of senescent cells.  

Keywords: embryonic stem cells, aging, longevity, cell rejuvination 

 

 

 

http://www.library.pitt.edu/
http://www.pitt.edu/
http://www.library.pitt.edu/articles/digpubtype/index.html
http://www.upress.pitt.edu/upressIndex.aspx