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Cyclin D1 Overexpression Permits the Reproducible Detection of Senescent Human Vascular Smooth Muscle Cells
Author(s) -
BURTON DOMINICK G. A.,
SHEERIN ANGELA N.,
OSTLER ELIZABETH L.,
SMITH KAYE,
GILES PETER J.,
LOWE JILL,
RHYSWILLIAMS WILLIAM,
KIPLING DAVID G.,
FARAGHER RICHARD G. A.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1404.026
Subject(s) - senescence , vascular smooth muscle , downregulation and upregulation , microbiology and biotechnology , biology , cyclin d1 , mitosis , myocyte , transcriptome , cell cycle , cell , gene expression , endocrinology , biochemistry , gene , smooth muscle
: 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 cellsin 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 β‐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.