The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions
Open accessAbstract
Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16 INK4a/pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions by cultivating the telomerase-expressing cells on feeder layers avoids the growth arrest associated with increased p16 INK4a. These results do not support a telomere-independent mechanism of replicative aging.
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“Likewise, telomere-dependent replicative senescence is thought to depend primarily on the p53 pathway (Ramirez et al., 2001; Herbig et al., 2004).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Ramirez et al., 2001
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“although cellular senescence in vitro may also occur without detectable DDR [31,32].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [31]
In the citing paper
“Telomerase activation and the resulting telomere-length maintenance leads to the bypass of senescence and ultimately to cell immortalization23,26,27.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [26]
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Cited by
Sorted by citations
Cellular senescence: when bad things happen to good cells
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BackgroundThe essence of senescence: Figure 1.
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Metadata
- Authors
- Ramirez, R. D., Morales, C. P., Herbert, B.-S., Rohde, J. M., Passons, C., Shay, J. W., & Wright, W. E.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2001-02-15
- Volume
- 15
- Issue
- 4
- Pages
- 398-403
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC312628
- OpenAlex
- W2136840198
- Cited by
- 444
- References
- 0
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 11 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 12 · 2015: 9 · 2014: 14 · 2013: 8 · 2012: 12
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institute on Aging (AG 01228, R01AG001228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- replicative senescence, telomere shortening, telomerase, p16INK4a, retinoblastoma protein, cell immortalization, feeder layer, epithelial-mesenchymal interactions, keratinocytes, breast epithelial cells, fibroblasts, culture conditions
- MeSH terms
- Animals, Cell Division, Cell Line, Transformed, Culture Media, Epithelial Cells, Female, Fibroblasts, Humans, Mammary Glands, Animal, Skin, Keratinocytes, 3T3 Cells, Telomere, Cellular Senescence, Telomerase, Cyclin-Dependent Kinase Inhibitor p16, Mice
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