A continuous correlation between oxidative stress and telomere shortening in fibroblasts.
Telomere shortening in cells with low intrinsic telomerase activity like fibroblasts is governed by various mechanisms including the so-called end-replication problem, end processing and oxidative DNA damage. To assess the impact of oxidative stress on telomere shortening rates, we compared telomere shortening rates measured in fibroblasts from two different donor species (human and sheep) under both pro- and antioxidative culture regimes. Over an almost 50-fold change in peroxide indicator dye fluorescence intensity, we found a continuous, exponential correlation between cellular oxidative stress levels and telomere shortening rates, which was independent of donor species and cell strain. This correlation suggests stress-mediated telomere DNA damage as an important determinant of telomere shortening.
Richter
Torsten
T
Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne NE4 6BE, UK.
von Zglinicki
Thomas
T
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology; D010545:Peroxides / Q000032:analysis; D012756:Sheep; D016615:Telomere / Q000648:ultrastructure*
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D010545:Peroxides; C029217:phenyl-N-tert-butylnitrone; D010100:Oxygen