Cited by 119Autophagy in Disease and TherapyTelomeres, Telomerase, and SenescenceCell death mechanisms and regulation

Senescent Keratinocytes Die by Autophagic Programmed Cell Death

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Gosselin, Karo, Deruy, Emeric, Martien, Sébastien, Vercamer, Chantal, Bouali, Fatima, Dujardin, Thibault, Slomianny, Christian, Houel-Renault, Ludivine +3 more·2009·The American Journal of Pathology

Abstract

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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Crossref · 10.2353/ajpath.2009.080332

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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
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2009-02
Volume
174
Issue
2
Pages
423-435
ISSN
0002-9440 (ISSN-L)
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
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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