| Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver. | |
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MedLine Citation:
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PMID: 22504828 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIM: Telomeres, a validated biomarker of ageing, 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 studied the effect of aging in "normal" liver tissue, but 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. METHOD: We developed a robust large volume four-colour quantitative fluorescent in situ hybridisation (Q-FISH) technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4+ and CD8+ 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 post transplant. RESULTS: Cholangiocytes had significantly longer telomeres compared to all other intrahepatic lineages over a wide age range (p < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e. Kupffer (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. (HEPATOLOGY 2012.). |
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Authors:
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Suman Verma; Phaedra Tachtatzis; Sue Penrhyn-Lowe; Cinzia Scarpini; Diana Jurk; Thomas Von Zglinicki; Nick Coleman; Graeme Jm Alexander |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-13 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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Division of Gastroenterology & Hepatology, University Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK, CB2 2QQ. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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