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Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

MnSOD upregulation induces autophagic programmed cell death in senescent keratinocytes

Emeric Deruy1, Karo Gosselin, Chantal Vercamer

  • 1Université Lille Nord de France, Lille, France.

Plos One
|September 22, 2010
PubMed

Insights

Senescent keratinocytes undergo programmed cell death via autophagy, not apoptosis. This process is triggered by increased oxidative stress and damage to mitochondria and the nucleus.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • Cellular senescence is a state of irreversible growth arrest.
  • Oxidative stress and telomere attrition are key inducers of senescence.
  • Senescent keratinocytes exhibit high macroautophagic activity leading to cell death.

Purpose of the Study:

  • To investigate the mechanisms activating autophagic cell death in senescent keratinocytes.
  • To elucidate the role of oxidative stress and specific molecular pathways in this process.

Main Methods:

  • Analysis of senescent keratinocyte corpses for oxidative damage and autophagic markers.
  • Manipulation of hydrogen peroxide (H2O2) levels using catalase, MnSOD overexpression, and exogenous H2O2.
  • Assessment of autophagy using Lysotracker staining, LC3 vesiculation, and transmission electron microscopy.
  • Inhibition of autophagy using 3-methyladenine and anti-Atg5 siRNAs.

Main Results:

  • Senescent keratinocyte corpses show oxidatively damaged mitochondria and nuclei co-localized with autophagosomes.
  • Reducing H2O2 levels decreased corpse formation, while increasing H2O2 or MnSOD reproduced it.
  • H2O2-induced cell death involved autophagosome accumulation and was partially blocked by autophagy inhibitors.
  • Autophagic cell death was linked to upregulated MnSOD and subsequent oxidative damage.

Conclusions:

  • Autophagic cell death is activated in senescent keratinocytes.
  • Upregulation of MnSOD leads to oxidative damage, triggering this autophagic death pathway.
  • This pathway represents a novel mechanism of cell death in senescent skin cells.

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