Cited by 603Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceSingle-cell and spatial transcriptomics

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

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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·2006·Nature

DOI 10.1038/nature04844

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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.

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Authors: Bahar, R., Hartmann, C. H., Rodriguez, K. A., Denny, A. D., Busuttil, R. A., Dollé, M. E. T., Calder, R. B., Chisholm, G. B., Pollock, B. H., Klein, C. A., & Vijg, J.
Affiliations: Buck Institute for Research on Aging (US)
Institut für Immunologie (DE)
The University of Texas at San Antonio Health Science Center (US)
National Institute for Public Health and the Environment (NL)
Corresponding author: Vijg, Jan
ORCID: Hartmann, Claudia H.
Busuttil, Rita A.
Dollé, Martijn E. T.
Calder, R. Brent
Chisholm, Gary B.
Pollock, Brad H.
Klein, Christoph A.
Vijg, Jan
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-06
Volume: 441
Issue: 7096
Pages: 1011-1014
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature04844
OpenAlex: W2067432938
Cited by: 603
References: 20
Citations by year: 2026: 22 · 2025: 20 · 2024: 26 · 2023: 38 · 2022: 25 · 2021: 29 · 2020: 35 · 2019: 42 · 2018: 29 · 2017: 40 · 2016: 28 · 2015: 35 · 2014: 28 · 2013: 22 · 2012: 29
FWCI: 10.70
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
Rivm (National Institute for Public Health and the Environment) (submittedVersion, other-oa)
Funders: National Institute on Aging (R36AG033401, P01AG017242)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords: aging, transcriptional noise, cardiomyocytes, genome rearrangement, genotoxic stress, hydrogen peroxide, stochastic gene expression, heart
MeSH terms: Aging, Animals, Heart, Hydrogen Peroxide, Male, Mice, Inbred C57BL, Myocardium, RNA, Messenger, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, Mice

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

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