Document Detail

Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells.
MedLine Citation:
PMID:  12881434     Owner:  NLM     Status:  MEDLINE    
Telomere shortening limits the regenerative capacity of primary cells in vitro by inducing cellular senescence characterized by a permanent growth arrest of cells with critically short telomeres. To test whether this in vitro model of cellular senescence applies to impaired organ regeneration induced by telomere shortening in vivo, we monitored liver regeneration after partial hepatectomy in telomerase-deficient mice. Our study shows that telomere shortening is heterogeneous at the cellular level and inhibits a subpopulation of cells with critically short telomeres from entering the cell cycle. This subpopulation of cells with impaired proliferative capacity shows senescence-associated beta-galactosidase activity, while organ regeneration is accomplished by cells with sufficient telomere reserves that are capable of additional rounds of cell division. This study provides experimental evidence for the existence of an in vivo process of cellular senescence induced by critical telomere shortening that has functional impact on organ regeneration.
A Satyanarayana; S U Wiemann; J Buer; J Lauber; K E J Dittmar; T Wüstefeld; M A Blasco; M P Manns; K L Rudolph
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  22     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-25     Completed Date:  2003-09-23     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  4003-13     Citation Subset:  IM    
Department of Gastroenterology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
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MeSH Terms
Cell Cycle*
Cell Division
Liver / cytology,  ultrastructure
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
RNA / genetics,  physiology
Telomerase / genetics,  physiology
Reg. No./Substance:
0/telomerase RNA; 63231-63-0/RNA; EC

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