Low oxygen delays fibroblast senescence despite shorter telomeres.
It has been widely accepted that telomere shortening acts as a cell division counting mechanism that beyond a set critical length signals cells to enter replicative senescence. In this study, we demonstrate that by simply lowering the oxygen content of the cell culture environment 10-fold (20-2%) extends the replicative lifespan of fetal bovine fibroblasts at least five-times (30-150 days). Although, low oxygen fibroblasts display a slightly slower rate (P > 0.05) of telomere attrition than their high oxygen counterparts (171 bp versus 182 bp/PD), late passage fibroblasts (>50 PD) that have extended their replicative capacity under low oxygen conditions exhibited significantly (P < 0.05) shorter telomere lengths (11,135 +/- 467 bp) compared to senescent cells (25-34 PD) cultured under high oxygen conditions (14,827 +/- 1173 bp). There was a significant increase (P < 0.05) in chromosomal abnormalities with continual cell division under both high and low oxygen environments, however, fibroblasts displayed a significant reduction (P < 0.001) in chromosomal abnormalities at low oxygen tensions compared to those under 20% oxygen. These apparent protective effects on telomere shortening, delayed senescence and reduced chromosomal aberrations may be attributed to the up-regulation of telomerase activity observed for fibroblasts cultured under low oxygen. These results are consistent with the idea that a critically short telomere length may not be the sole trigger of replicative senescence, but may be regulated by the integrity of telomere structure itself and/or the amount of oxidative DNA damage in the cell.
Betts
Dean H
DH
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, N1G 2W1. bettsd@uoguelph.ca
Perrault
Steven D
SD
King
W Allan
WA
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D010100:Oxygen / Q000378:metabolism*; D016615:Telomere
D010100:Oxygen