Document Detail


Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch.
MedLine Citation:
PMID:  20231314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Regenerative capacity is progressively lost with age. Here we show that pregnancy markedly improved liver regeneration in aged mice concomitantly with inducing a switch from proliferation-based liver regeneration to a regenerative process mediated by cell growth. We found that the key mediator of this switch was the Akt/mTORC1 pathway; its inhibition blocked hypertrophy, while increasing proliferation. Moreover, pharmacological activation of this pathway sufficed to induce the hypertrophy module, mimicking pregnancy. This treatment dramatically improved hepatic regenerative capacity and survival of old mice. Thus, cell growth-mediated mass reconstitution, which is relatively resistant to the detrimental effects of aging, is employed in a physiological situation and holds potential as a therapeutic strategy for ameliorating age-related functional deterioration.
Authors:
Yuval Gielchinsky; Neri Laufer; Efi Weitman; Rinat Abramovitch; Zvi Granot; Yehudit Bergman; Eli Pikarsky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  24     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-16     Completed Date:  2010-03-26     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  543-8     Citation Subset:  IM    
Affiliation:
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Ein Kerem, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
Antibiotics, Antineoplastic / pharmacology
Cell Proliferation
Female
Hepatectomy
Hepatocytes / cytology,  drug effects
Hyperplasia / metabolism
Hypertrophy / metabolism
Liver / cytology,  drug effects,  growth & development,  metabolism*,  surgery
Liver Regeneration / drug effects,  physiology*
Male
Mice
Mice, Inbred C57BL
Pregnancy
Proteins
Signal Transduction / drug effects
Sirolimus / pharmacology
Transcription Factors / metabolism*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Proteins; 0/Transcription Factors; 0/mechanistic target of rapamycin complex 1; 53123-88-9/Sirolimus
Comments/Corrections

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