Increased cell-to-cell variation in gene expression in ageing mouse heart.

2.50
Hdl Handle:
http://hdl.handle.net/10029/5612
Title:
Increased cell-to-cell variation in gene expression in ageing mouse heart.
Authors:
Bahar, Rumana; Hartmann, Claudia H; Rodriguez, Karl A; Denny, Ashley D; Busuttil, Rita A; Dollé, Martijn E T; Calder, R Brent; Chisholm, Gary B; Pollock, Brad H; Klein, Christoph A; Vijg, Jan
Abstract:
The accumulation of somatic DNA damage has been implicated as a cause of ageing in metazoa. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by dissociating single cardiomyocytes from fresh heart samples of both young and old mice, followed by global mRNA amplification and quantification of mRNA levels in a panel of housekeeping and heart-specific genes. Although gene expression levels already varied among cardiomyocytes from young heart, this heterogeneity was significantly elevated at old age. We had demonstrated previously an increased load of genome rearrangements and other mutations in the heart of aged mice. To confirm that increased stochasticity of gene expression could be a result of increased genome damage, we treated mouse embryonic fibroblasts in culture with hydrogen peroxide. Such treatment resulted in a significant increase in cell-to-cell variation in gene expression, which was found to parallel the induction and persistence of genome rearrangement mutations at a lacZ reporter locus. These results underscore the stochastic nature of the ageing process, and could provide a mechanism for age-related cellular degeneration and death in tissues of multicellular organisms.
Citation:
Nature 2006, 441(7096):1011-4
Issue Date:
22-Jun-2006
URI:
http://hdl.handle.net/10029/5612
DOI:
10.1038/nature04844
PubMed ID:
16791200
Type:
Article
Language:
en
ISSN:
1476-4687
Appears in Collections:
Miscellaneous

Full metadata record

DC FieldValue Language
dc.contributor.authorBahar, Rumana-
dc.contributor.authorHartmann, Claudia H-
dc.contributor.authorRodriguez, Karl A-
dc.contributor.authorDenny, Ashley D-
dc.contributor.authorBusuttil, Rita A-
dc.contributor.authorDollé, Martijn E T-
dc.contributor.authorCalder, R Brent-
dc.contributor.authorChisholm, Gary B-
dc.contributor.authorPollock, Brad H-
dc.contributor.authorKlein, Christoph A-
dc.contributor.authorVijg, Jan-
dc.date.accessioned2006-10-26T13:21:47Z-
dc.date.available2006-10-26T13:21:47Z-
dc.date.issued2006-06-22-
dc.identifier.citationNature 2006, 441(7096):1011-4en
dc.identifier.issn1476-4687-
dc.identifier.pmid16791200-
dc.identifier.doi10.1038/nature04844-
dc.identifier.urihttp://hdl.handle.net/10029/5612-
dc.description.abstractThe accumulation of somatic DNA damage has been implicated as a cause of ageing in metazoa. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by dissociating single cardiomyocytes from fresh heart samples of both young and old mice, followed by global mRNA amplification and quantification of mRNA levels in a panel of housekeeping and heart-specific genes. Although gene expression levels already varied among cardiomyocytes from young heart, this heterogeneity was significantly elevated at old age. We had demonstrated previously an increased load of genome rearrangements and other mutations in the heart of aged mice. To confirm that increased stochasticity of gene expression could be a result of increased genome damage, we treated mouse embryonic fibroblasts in culture with hydrogen peroxide. Such treatment resulted in a significant increase in cell-to-cell variation in gene expression, which was found to parallel the induction and persistence of genome rearrangement mutations at a lacZ reporter locus. These results underscore the stochastic nature of the ageing process, and could provide a mechanism for age-related cellular degeneration and death in tissues of multicellular organisms.en
dc.format.extent395734 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.titleIncreased cell-to-cell variation in gene expression in ageing mouse heart.en
dc.typeArticleen
dc.format.digYES-

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