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

Rumana Bahar, Claudia H. Hartmann, Karl A. Rodriguez, Ashley D. Denny, Rita A. Busuttil, Martijn E T Dollé, R. Brent Calder, Gary B. Chisholm, Bradley H Pollock, Christoph A. Klein, Jan Vijg

Research output: Contribution to journalArticle

336 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1011-1014
Number of pages4
JournalNature
Volume441
Issue number7096
DOIs
StatePublished - Jun 22 2006
Externally publishedYes

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Gene Expression
Genome
Cardiac Myocytes
DNA Damage
Housekeeping
Messenger RNA
Mutation
Hydrogen Peroxide
Noise
Fibroblasts
Genes

ASJC Scopus subject areas

  • General

Cite this

Bahar, R., Hartmann, C. H., Rodriguez, K. A., Denny, A. D., Busuttil, R. A., Dollé, M. E. T., ... Vijg, J. (2006). Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature, 441(7096), 1011-1014. https://doi.org/10.1038/nature04844

Increased cell-to-cell variation in gene expression in ageing mouse heart. / 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, Bradley H; Klein, Christoph A.; Vijg, Jan.

In: Nature, Vol. 441, No. 7096, 22.06.2006, p. 1011-1014.

Research output: Contribution to journalArticle

Bahar, R, Hartmann, CH, Rodriguez, KA, Denny, AD, Busuttil, RA, Dollé, MET, Calder, RB, Chisholm, GB, Pollock, BH, Klein, CA & Vijg, J 2006, 'Increased cell-to-cell variation in gene expression in ageing mouse heart', Nature, vol. 441, no. 7096, pp. 1011-1014. https://doi.org/10.1038/nature04844
Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dollé MET et al. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature. 2006 Jun 22;441(7096):1011-1014. https://doi.org/10.1038/nature04844
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, Bradley H ; Klein, Christoph A. ; Vijg, Jan. / Increased cell-to-cell variation in gene expression in ageing mouse heart. In: Nature. 2006 ; Vol. 441, No. 7096. pp. 1011-1014.
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