When cells get stressed: an integrative view of cellular senescence
Open accessAbstract
Cells entering a state of senescence undergo a permanent cell cycle arrest, accompanied by a set of functional and morphological changes. Senescence of cells occurs following an extended period of proliferation in culture or in response to various physiologic stresses, yet little is known about the role this phenomenon plays in vivo. The study of senescence has focused largely on its hypothesized role as a barrier to extended cell division, governed by a division-counting mechanism in the form of telomere length. Here, we discuss the biological functions of cellular senescence and suggest that it should be viewed in terms of its role as a general cellular stress response program, rather than strictly as a barrier to unlimited cycles of cell growth and division. We also discuss the relative roles played by telomere shortening and telomere uncapping in the induction of senescence.
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Critically short telomeres trigger the onset of senescence through a process that may involve loss of the t loop structure and/or loss of protective proteins.
“Critically short telomeres trigger the onset of senescence through a process that may involve loss of the t loop structure and/or loss of protective proteins (referred to as “uncapping”).”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Ben-Porath and Weinberg, 2004
Uncapped telomeres are recognized by the cell cycle checkpoint machinery as DNA damage, leading to cell cycle arrest.
“Such uncapped telomeres are then recognized by the cell cycle checkpoint machinery as DNA damage, leading to cell cycle arrest (Ben-Porath and Weinberg, 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Ben-Porath and Weinberg, 2004
ROS and many other DNA-damaging agents can cause cells to enter senescence.
“ROS and many other DNA-damaging agents can cause cells to enter a state of irreversible cell cycle arrest accompanied by characteristic morphologic and functional alterations, termed senescence (Ben-Porath and Weinberg, 2004”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Ben-Porath and Weinberg, 2004
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- Authors
- Ben-Porath, I., & Weinberg, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Weinberg, Robert A.
- ORCID
- Weinberg, Robert A.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-01-01
- Volume
- 113
- Issue
- 1
- Pages
- 8-13
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC300889
- OpenAlex
- W2079742382
- Cited by
- 404
- References
- 54
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 12 · 2023: 9 · 2022: 14 · 2021: 15 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 14 · 2015: 13 · 2014: 22 · 2013: 19 · 2012: 20
- FWCI
- 21.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cell death mechanisms and regulation
- Keywords
- cellular senescence, cell cycle arrest, cellular stress response, telomere shortening, telomere uncapping, senescence-associated secretory phenotype
- MeSH terms
- Animals, Cell Cycle, Cell Division, Humans, Models, Biological, Models, Genetic, Genes, Tumor Suppressor, Telomere, Cellular Senescence
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