Document Detail


Cyclin D1 overexpression permits the reproducible detection of senescent human vascular smooth muscle cells.
MedLine Citation:
PMID:  18056951     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The senescence of mitotic cells is hypothesized to play a causal role in organismal aging. Cultures of normal human cells become senescent in vitro as a result of a continuous decline in the mitotic fraction from cell turnover. However, one potential barrier to the evaluation of the frequency and distribution of senescent cells in tissues is the absence of a panel of robust markers for the senescent state. In parallel with an analysis of the growth kinetics of human vascular smooth muscle cells, we have undertaken transcriptomic comparisons of early- and late-passage cultures of human vascular smooth muscle cells to identify potential markers that can distinguish between senescent and growth-competent cells. A wide range of genes are upregulated at senescence in human vascular smooth muscle cells. In particular, we have identified a 12-fold upregulation of expression in the cyclin D1 message, which is reflected in a concomitant upregulation at the protein level. Quantitative cytochemical analysis of senescent and growing vascular smooth muscle cells indicates that cyclin D1 reactivity is a considerably better marker of replicative senescence than senescence-associated beta-galactosidase activity. We have applied this new marker (in combination with Ki67, COMET, and TUNEL staining) to the study of human vascular smooth muscle cells treated with resveratrol, a putative anti-aging molecule known to have significant effects on cell growth.
Authors:
Dominick G A Burton; Angela N Sheerin; Elizabeth L Ostler; Kaye Smith; Peter J Giles; Jill Lowe; William Rhys-Williams; David G Kipling; Richard G A Faragher
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1119     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-12-06     Completed Date:  2008-03-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20-31     Citation Subset:  IM    
Affiliation:
School of Pharmacy and Biomolecular Sciences, Cockcroft Building, University of Brighton, Brighton, East Sussex, BN2 4GJ, UK.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Biological Markers / metabolism
Cell Aging / physiology*
Cells, Cultured
Comet Assay
Cyclin D
Cyclins / biosynthesis*
Humans
In Situ Nick-End Labeling
Ki-67 Antigen / biosynthesis
Mitosis / physiology*
Muscle, Smooth, Vascular / cytology,  metabolism*
Myocytes, Smooth Muscle / cytology,  metabolism*
RNA, Messenger / biosynthesis
Transcription, Genetic / physiology*
Up-Regulation / physiology
beta-Galactosidase / biosynthesis
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cyclin D; 0/Cyclins; 0/Ki-67 Antigen; 0/RNA, Messenger; EC 3.2.1.23/beta-Galactosidase

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


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