Deep senescent human fibroblasts show diminished DNA damage foci but retain checkpoint capacity to oxidative stress.
Critically shortened telomeres trigger a DNA damage response in replicatively senescent cells. Here we report that while DNA damage foci can be detected in newly senescent cells, these foci eventually diminished in deep senescent cells. However, DNA checkpoint signalling and repair machinery in response to oxidative stress remain uncompromised in these deep senescent cells. Activation of p53 by oxidative stress is unaffected despite a marked decrease in expression of platelet-derived growth factor alpha-receptor. These findings suggest that cellular senescence is not a static process hence care must be taken in the selection of biomarkers of senescence in studies of ageing.
Chen
Jian-Hua
JH
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom. jh36@cam.ac.uk
Ozanne
Susan E
SE
D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D020796:Receptor, Platelet-Derived Growth Factor alpha