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Cited by 209Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsGenomics and Chromatin Dynamics

Senescence-specific gene expression fingerprints reveal cell-type-dependent physical clustering of up-regulated chromosomal loci

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Zhang, Hong, Pan, Kuang-Hung, Cohen, Stanley N.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2627983100PMC PMC152278
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Abstract

Replicative senescence is the state of irreversible proliferative arrest that occurs as a concomitant of progressive telomere shortening. By using cDNA microarrays and the gabriel system of computer programs to apply domain-specific and procedural knowledge for data analysis, we investigated global changes in gene transcription occurring during replicative senescence in human fibroblasts and mammary epithelial cells (HMECs). Here we report the identification of transcriptional “fingerprints” unique to senescence, the finding that gene expression perturbations during senescence differ greatly in fibroblasts and HMECs, and the discovery that despite the disparate nature of the chromosomal loci affected by senescence in fibroblasts and HMECs, the up-regulated loci in both types of cells show physical clustering. This clustering, which contrasts with the random distribution of genes down-regulated during senescence or up-regulated during reversible proliferative arrest (i.e., quiescence), supports the view that replicative senescence is associated with alteration of chromatin structure.

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  • Senescent cells acquire many changes in gene expression, including increased expression of secreted proteins.

    “Senescent cells acquire many changes in gene expression, mostly documented as altered mRNA abundance, including increased expression of secreted proteins [ 33 – 41 ].”

    From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [33]

    The Results report hundreds of changes in transcript abundance during senescence in human fibroblasts, supporting the claim about altered gene expression measured as mRNA. They identify up-regulated genes encoding membrane-associated proteins, but the passages in our copy do not establish increased expression of secreted proteins; membrane-associated is not the same as secreted. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Among the genes that are upregulated by the senescence response, many encode secreted proteins that can alter the tissue microenvironment and thus alter tissue structure and function.

    “In addition, among the genes that are upregulated by the senescence response (Shelton et al., 1999; Chang et al., 2000; Zhang et al., 2003), many encode secreted proteins that can alter the tissue microenvironment thus alter tissue structure and function.”

    From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Zhang et al., 2003

    The Results report 376 genes up-regulated specifically during senescence in human fibroblasts. They describe many annotated up-regulated genes as membrane-associated, but do not establish that many encode secreted proteins or that those proteins alter the tissue microenvironment, structure, or function. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Many of the genes that are upregulated in senescent cells are physically clustered.

    “Whatever the case, it is interesting that many of the genes that are upregulated in senescent cells are physically clustered (Zhang et al., 2003).”

    From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Zhang et al., 2003

  • In senescence-associated transcriptome signatures, genes involved in growth factor signaling, cell cycle progression, DNA replication, and mitosis progression control are downregulated.

    “In these senescence-associated signatures, genes involved in growth factor signaling, cell cycle progression, DNA replication, and mitosis progression control are downregulated [68,136,137,138,139,140].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [138]

  • Fibroblasts undergoing replicative senescence in vitro also show gene expression changes caused by telomere shortening.

    “Gene expression changes due to telomere shortening also occur in vitro in fibroblasts undergoing replicative senescence122.”

    From The telomere syndromes (2012) · cites this paper as [122]

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Cited by

Sorted by citations

Authors
Zhang, H., Pan, K.-H., & Cohen, S. N.
Affiliations
Stanford Medicine (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-03-07
Volume
100
Issue
6
Pages
3251-3256
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2627983100
PMC
PMC152278
OpenAlex
W2085444106
Cited by
209
References
13
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 9 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 12 · 2015: 14 · 2014: 11 · 2013: 12 · 2012: 15
FWCI
7.47
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
replicative senescence, chromatin structure, telomere shortening, human fibroblasts, mammary epithelial cells, quiescence, transcriptional regulation
MeSH terms
Breast, Cell Division, Cell Line, Chromosomes, Human, Epithelial Cells, Female, Fibroblasts, Humans, Up-Regulation, Cellular Senescence, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling

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