Although reactive oxygen species have been proposed to play a major role in the 
aging process, the exact molecular mechanisms remain elusive. In this study we 
investigate the effects of a perturbation in the ratio of Cu/Zn-superoxide 
dismutase activity (Sod1 dismutases .O2-to H2O2) to glutathione peroxidase 
activity (Gpx1 catalyses H2O2 conversion to H2O) on cell growth and development. 
Our data demonstrate that Sod1 transfected cell lines that have an elevation in 
the ratio of Sod1 activity to Gpx1 activity produce higher levels of H2O2 and 
exhibit well characterised markers of cellular senescence viz. slower 
proliferation and altered morphology. On the contrary, Sod1 transfected cell 
lines that have an unaltered ratio in the activity of these two enzymes, have 
unaltered levels of H2O2 and fail to show characteristics of senescence. 
Furthermore, fibroblasts established from individuals with Down syndrome have an 
increase in the ratio of Sod1 to Gpx1 activity compared with corresponding 
controls and senesce earlier. Interestingly, cells treated with H2O2 also show 
features of senescence and/or senesce earlier. We also show that Cip1 mRNA 
levels are elevated in Down syndrome cells, Sod1 transfectants with an altered 
Sod1 to Gpx1 activity ratio and those treated with H2O2, thus suggesting that 
the slow proliferation may be mediated by Cip1. Furthermore, our data 
demonstrate that Cip1 mRNA levels are induced by exposure of cells to H2O2. 
These data give valuable insight into possible molecular mechanisms that 
contribute tribute to cellular senescence and may be useful in the evolution of 
therapeutic strategies for aging.