Premature senescence of mesothelial cells is associated with non-telomeric DNA damage

Krzysztof Ksiazek, João F. Passos, Sharon Olijslagers, Gabriele Saretzki, Carmen Martin-Ruiz, Thomas von Zglinicki

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Human peritoneal mesothelial cells (HPMCs) senesce in vitro after barely few population doublings. In this report, we show that senescence of HPMCs is associated with increased accumulation of γ-H2A.X foci, which reveal DNA double-strand breaks. Of note, already early-passage cultures contain a considerable fraction (44 ± 10%) of cells bearing γ-H2A.X foci. The γ-H2A.X foci localize predominantly to non-telomeric DNA, either in young or senescent cells. Moreover, HPMCs seem to have unusually short telomeres (∼3.5 kbp) despite the presence of active telomerase. These telomeres do not shorten during senescence, but the activity of telomerase decreases to undetectable levels. In addition, senescence of HPMCs is associated with mitochondrial dysfunction, as manifested by increased production of reactive oxygen species and reduced mitochondrial membrane potential. These results may indicate that premature senescence of HPMCs is largely related to oxidative stress-induced DNA damage in non-telomeric regions of the genome.

Original languageEnglish (US)
Pages (from-to)707-711
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume362
Issue number3
DOIs
StatePublished - Oct 26 2007

Keywords

  • DNA damage
  • Mesothelial cells
  • Oxidative stress
  • Premature senescence
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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