Low oxygen delays fibroblast senescence despite shorter telomeres |
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Authors: | Dean H Betts Steven D Perrault W Allan King |
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Institution: | (1) Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, N1G 2W1 |
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Abstract: | 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. |
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Keywords: | Bovine Cellular senescence Chromosome Oxygen tension Proliferative lifespan Telomere and Telomerase |
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