| In response to external oxidative stress/DNA damaging agents, mammalian cells may choose one of the following pathways to avoid propagation of the damaged cells: repair the DNA and proceed with the normal cell cycle trigger apoptosis or undergo senescence to block cell division. Working with NHFs, we have observed that quiescent fibroblasts, unlike dividing fibroblasts, do not undergo apoptosis when subjected to a high dose of external oxidative stress but become senescent instead. Our results have indicated that p21 and MnSOD over-expression in quiescent cells is highly correlated to resistance to external oxidative stress and senescence induction. Furthermore, we observed that fibroblasts harvested from individuals diagnosed with Alzheimer's disease have a higher amount of endogenous ROS and double stranded DNA breaks than NHFs, leading to an earlier onset of replicative senescence. Consistent with higher ROS levels, AD fibroblasts have up-regulated expression of MnSOD and decreased levels of non-selenium glutathione peroxidase. |
