Senescent Keratinocytes Die by Autophagic Programmed Cell Death
Open accessAbstract
Normal cells reach senescence after a specific time and number of divisions, leading ultimately to cell death. Although escape from this fate may be a requisite step in neoplastic transformation, the mechanisms governing senescent cell death have not been well investigated. We show here, using normal human epidermal keratinocytes, that no apoptotic markers appear with senescence. In contrast, the expression of several proteins involved in the regulation of macroautophagy, notably Beclin-1 and Bcl-2, was found to change with senescence. The corpses occurring at the senescence growth plateau displayed a large central area delimited by the cytokeratin network that contained a huge quantity of autophagic vacuoles, the damaged nucleus, and most mitochondria. 3-methyladenine, an inhibitor of autophagosome formation, but not the caspase inhibitor zVAD, prevented senescent cell death. We conclude that senescent cells do not die by apoptosis, but as a result of high macroautophagic activity that targets the primary vital cell components.
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Increased cellular granularity is typically associated with senescence and autophagy.
“Increased cellular granularity is typically associated with senescence and autophagy15,16.”
From AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields) (2018) · cites this paper as [16]
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- Authors
- Gosselin, K., Deruy, E., Martien, S., Vercamer, C., Bouali, F., Dujardin, T., Slomianny, C., Houel-Renault, L., Chelli, F., De Launoit, Y., & Abbadie, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Corresponding author
- Abbadie, Corinne
- ORCID
- Abbadie, Corinne
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 174
- Issue
- 2
- Pages
- 423-435
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2630552
- OpenAlex
- W2059280539
- Cited by
- 119
- References
- 71
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- cellular senescence, macroautophagy, keratinocytes, Beclin-1, Bcl-2, apoptosis, 3-methyladenine, autophagosomes, epidermal keratinocytes, oncogenic transformation
- MeSH terms
- Beclin-1, Autophagy, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Membrane Proteins, Blotting, Western, Keratinocytes, Gene Expression, Cellular Senescence, Proto-Oncogene Proteins c-bcl-2, In Situ Nick-End Labeling, Microscopy, Electron, Transmission, Apoptosis Regulatory Proteins
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