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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.
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
refterms.dateFOA2018-12-18T13:48:57Z
html.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.


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