Altered gene expression during cellular aging

The limited division potential of normal human diploid fibroblasts in culture represents a model system for cellular aging. Observations indicate cellular senescence is an active process. Senescent cells, although unable to divide, are actively metabolizing. Hybrids from fusion of normal and immortal human cells exhibit limited division potential, suggesting that the phenotype of cellular senescence is dominant and supporting the hypothesis that senescence is genetically programmed. Fusion of immortal human cell lines with each other has identified four complementation groups for indefinite division. This indicates that a limited number of specific genes or processes are involved in senescence. Senescent cells express highly abundant DNA synthesis inhibitory messenger RNAs and produce a surface membrane associated protein inhibitor of DNA synthesis not expressed in young cells. Senescent cell membranes were used as immunogen to generate three monoclonal antibodies reacting specifically with senescent but not young cells in several normal human cell lines. We have also found that fibronectin messenger RNA accumulates to high levels in senescent cells. The role of these changes in gene expression in senescence is being explored.Key words: cellular senescence, human cells.

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Faculty Opinions recommendation of Comprehensive sampling of gene expression in human cell lines with massively parallel signature sequencing.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1012584.188502 ◽

2003 ◽

Author(s):

Vishvanath Nene

Keyword(s):

Gene Expression ◽

Cell Lines ◽

Human Cell ◽

Massively Parallel Signature Sequencing ◽

Massively Parallel ◽

Human Cell Lines ◽

Parallel Signature Sequencing

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NTP-mediated changes of gene expression patterns in human cell lines

2013 Abstracts IEEE International Conference on Plasma Science (ICOPS) ◽

10.1109/plasma.2013.6633300 ◽

2013 ◽

Author(s):

Lena Bundscherer ◽

Anke Schmidt ◽

Annemarie Barton ◽

Sybille Hasse ◽

Kristian Wende ◽

...

Keyword(s):

Gene Expression ◽

Cell Lines ◽

Human Cell ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Human Cell Lines

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Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-1

Molecular and Cellular Biology ◽

10.1128/mcb.13.10.6036-6043.1993 ◽

1993 ◽

Vol 13 (10) ◽

pp. 6036-6043

Author(s):

T Ogata ◽

D Ayusawa ◽

M Namba ◽

E Takahashi ◽

M Oshimura ◽

...

Keyword(s):

Cell Lines ◽

Human Cell ◽

Human Fibroblasts ◽

Fibroblast Cell ◽

Chromosome 7 ◽

In Vitro Mutagenesis ◽

Human Cell Lines ◽

First Case ◽

Normal Human

Using nontumorigenic immortalized human cell lines KMST-6 (KMST) and SUSM-1 (SUSM), we attempted to identify the chromosome that carries a putative senescence-related gene(s). These cell lines are the only ones that have been established independently from normal human diploid fibroblasts following in vitro mutagenesis. We first examined restriction fragment length polymorphisms on each chromosome of these immortalized cell lines and their parental cell lines and found specific chromosomal alterations common to these cell lines (a loss of heterozygosity in KMST and a deletion in SUSM) on the long arm of chromosome 7. In addition to these, we also found that introduction of chromosome 7 into these cell lines by means of microcell fusion resulted in the cessation of cell division, giving rise to cells resembling cells in senescence. Introduction of other chromosomes, such as chromosomes 1 and 11, on which losses of heterozygosity were also detected in one of the cell lines (KMST), to either KMST or SUSM cells or of chromosome 7 to several tumor-derived cell lines had no effect on their division potential. These results strongly suggest that a gene(s) affecting limited-division potential or senescence of normal human fibroblasts is located on chromosome 7, probably at the long arm of the chromosome, representing the first case in which a specific chromosome reverses the immortal phenotype of otherwise normal human cell lines.

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