The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Increased cell-to-cell variation in gene expression in ageing mouse heart
Open accessAbstract
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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In the citing paper
“Aging is associated with an increase in transcriptional noise (Bahar et al., 2006), and an aberrant production and maturation of many mRNAs (Harries et al., 2011; Nicholas et al., 2010).”
From The Hallmarks of Aging (2013) · cites this paper as Bahar et al., 2006
In the citing paper
“stochastic variations in gene expression in aged tissues are thought to be a contributing factor to age-associated organ decline even if gene expression across the tissue remains unaltered (59).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [59]
In the citing paper
“In a groundbreaking single cell study, RNA isolated from individual cardiomyocytes of young and old mice showed broad mosaicism in gene expression among cells within individual mice and increased differences in expression between cells.45.”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [45]
Citations
Cites
Stochasticity in gene expression: from theories to phenotypes
Kærn, M., Elston, T. C., Blake, W. J., & Collins, J. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1615 · Cited by 2,318
Understanding the odd science of aging
Kirkwood, T. B. L. (2005) · Cell · doi:10.1016/j.cell.2005.01.027 · Cited by 1,984
Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003) · Nature Cell Biology · doi:10.1038/ncb1024 · Cited by 1,116
THE MAINTENANCE OF THE ACCURACY OF PROTEIN SYNTHESIS AND ITS RELEVANCE TO AGEING
Orgel, L. E. (1963) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.49.4.517 · Cited by 968
Single-Cell Gene Expression Profiling
Levsky, J. M., Shenoy, S. M., Pezo, R. C., & Singer, R. H. (2002) · Science · doi:10.1126/science.1072241 · Cited by 526
Noise Minimization in Eukaryotic Gene Expression
Fraser, H. B., Hirsh, A. E., Giaever, G. N., Kumm, J., & Eisen, M. B. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020137 · Cited by 429
A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans
Rea, S. L., Wu, D., Cypser, J. R., Vaupel, J. W., & Johnson, T. E. (2005) · Nature Genetics · doi:10.1038/ng1608 · Cited by 414
Kang, P. M., Haunstetter, A., Aoki, H., Usheva, A., & Izumo, S. (2000) · Circulation Research · doi:10.1161/01.res.87.2.118 · Cited by 323
Contributions of low molecule number and chromosomal positioning to stochastic gene expression
Becskei, A., Kaufmann-Malaga, B., & van Oudenaarden, A. (2005) · Nature Genetics · doi:10.1038/ng1616 · Cited by 321
Combined transcriptome and genome analysis of single micrometastatic cells
Klein, C. A., Seidl, S., Petat‐Dutter, K., Offner, S., Geigl, J. B., Schmidt‐Kittler, O., Wendler, N., Passlick, B., Huber, R. M., Schlimok, G., et al. (2002) · Nature Biotechnology · doi:10.1038/nbt0402-387 · Cited by 303
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Zhang, J., Su, W., Duan, J., Sun, Y., & Liu, B. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100262
Quantitative Visualization of Sex Steroid Receptor Functions: AR and ERα
Bolt, M. J., Hartig, S. M., Szafran, A. T., Mediwala, S. N., Marcelli, M., & Mancini, M. A. (2011) · Springer eBooks · doi:10.1007/978-1-4614-1764-4_14
Signaling Pathways in Eukaryotic Stress, Aging, and Senescence: Common and Distinct Pathways
Das, R., Pandey, A., & Pandey, G. K. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2540-7_13
Metadata
- 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
- Venue
- Nature
- Published
- 2006-06
- Volume
- 441
- Issue
- 7096
- Pages
- 1011-1014
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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