Document Detail


Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver.
MedLine Citation:
PMID:  22504828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in "normal" liver tissue, but these studies were compromised by small sample size, limited age range, tissue derived from individuals with an increased risk of senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range (P < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [P = 0.0054] and stellate cells [P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells.
Authors:
Suman Verma; Phaedra Tachtatzis; Sue Penrhyn-Lowe; Cinzia Scarpini; Diana Jurk; Thomas Von Zglinicki; Nick Coleman; Graeme J M Alexander
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-27
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  56     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-05     Completed Date:  2013-01-17     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1510-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aging / genetics*
Bile Ducts / cytology*,  physiology
Cell Aging / genetics*
Cells, Cultured
Child, Preschool
Female
Hepatocytes / metabolism,  physiology*
Humans
In Situ Hybridization, Fluorescence
Kupffer Cells / cytology,  physiology
Liver / pathology*
Male
Middle Aged
Real-Time Polymerase Chain Reaction / methods
Reference Values
Reproducibility of Results
Risk Assessment
Sampling Studies
Sensitivity and Specificity
Telomere / genetics*,  physiology
Telomere Shortening / genetics
Young Adult
Grant Support
ID/Acronym/Agency:
G0900686//Medical Research Council

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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