Senescent fibroblasts resist apoptosis by downregulating caspase-3

Richard Marcotte, Chantale Lacelle, Eugenia Wang

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

In replicative senescence, cells undergo permanent exit from cell cycle traverse; this is traditionally thought to occur at the end of a culture's in vitro life span, after serial passaging. In general, the checkpoint for replicative senescence is found at the G 1/S border, controlled by the modulation of a battery of proteins, typified by gaining inhibitors of cell cycle traverse, such as cyclin-dependent kinases or RB hyperphosphorylation, and losing pro-proliferation gene expressions such as c-fos, c-myc, and a cadre of proliferation-dependent kinases. Here, we present evidence that replicatively senescent fibroblasts are resistant to apoptotic death, associated with a lack of key enzyme activities, caspase-3 being the chief executioner. This observation, coupled with our earlier report that senescent fibroblasts maintain persistently high levels of pro-survival factor Bcl-2, suggests that the molecular signaling program present in fibroblasts at the end of their in vitro life span may not only cater to the state of permanent exit from cell cycle traverse, but also dictate an inability to commit cellular suicide. Future experiments will reveal whether replicatively senescent fibroblasts that can neither proliferate nor die contribute to organismic aging, and whether their accumulation over time in tissue becomes detrimental to the normal aging process.

Original languageEnglish (US)
Pages (from-to)777-783
Number of pages7
JournalMechanisms of Ageing and Development
Volume125
Issue number10-11 SPEC. ISS.
DOIs
StatePublished - Oct 1 2004

Keywords

  • Microarray
  • Population doubling level
  • RT-PCR
  • Replicative senescence
  • Staurosporine

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Fingerprint Dive into the research topics of 'Senescent fibroblasts resist apoptosis by downregulating caspase-3'. Together they form a unique fingerprint.

  • Cite this