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- Title
Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts.
- Authors
Parrinello, Simona; Samper, Enrique; Krtolica, Ana; Goldstein, Joshua; Melov, Simon; Campisi, Judith
- Abstract
Most mammalian cells do not divide indefinitely, owing to a process termed replicative senescence. In human cells, replicative senescence is caused by telomere shortening, but murine cells senesce despite having long stable telomeres[SUP1]. Here, we show that the phenotypes of senescent human fibroblasts and mouse embryonic fibroblasts (MEFs) differ under standard culture conditions, which include 20% oxygen. MEFs did not senesce in physiological (3%) oxygen levels, but underwent a spontaneous event that allowed indefinite proliferation in 20% oxygen. The proliferation and cytogenetic profiles of DNA repair-deficient MEFs suggested that DNA damage limits MEF proliferation in 20% oxygen. Indeed, MEFs accumulated more DNA damage in 20% oxygen than 3% oxygen, and more damage than human fibroblasts in 20% oxygen. Our results identify oxygen sensitivity as a critical difference between mouse and human cells, explaining their proliferative differences in culture, and possibly their different rates of cancer and ageing.
- Subjects
FIBROBLASTS; OXYGEN; TELOMERES; DNA damage
- Publication
Nature Cell Biology, 2003, Vol 5, Issue 8, p741
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1024