Senescent fibroblasts resist apoptosis by downregulating caspase-3.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Marcotte, R; Lacelle, C; Wang, E

Published Date

  • October 2004

Published In

Volume / Issue

  • 125 / 10-11

Start / End Page

  • 777 - 783

PubMed ID

  • 15541772

Pubmed Central ID

  • 15541772

International Standard Serial Number (ISSN)

  • 0047-6374

Digital Object Identifier (DOI)

  • 10.1016/j.mad.2004.07.007

Language

  • eng

Conference Location

  • Ireland