Senescent keratinocytes die by autophagic programmed cell death.
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.
Gosselin
Karo
K
UMR8161, Institut de Biologie de Lille, Lille Cedex, France.
Deruy
Emeric
E
Martien
Sébastien
S
Vercamer
Chantal
C
Bouali
Fatima
F
Dujardin
Thibault
T
Slomianny
Christian
C
Houel-Renault
Ludivine
L
Chelli
Fazia
F
De Launoit
Yvan
Y
Abbadie
Corinne
C
D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D015153:Blotting, Western; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000473:pathology* / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis; D046529:Microscopy, Electron, Transmission; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2