Figure 2.

iPS system for the study of epigenetic rejuvenation. In (A) is shown the relationship of epigenetic instability (the y-axis) after introduction of the ‘reprogramming factors’ to the developmental potential of cells (the x-axis). After introduction of the reprogramming factors, cells set out on the path toward iPS cells and pass, after 4–7 days a zone of ‘epigenetic instability’ where the fate of the cells undergoing reprogramming is pliant. Using defined media, the ‘unstable’ cells can be forced down different developmental pathways giving rise to other cell linages (Efe et al. 2011). Of interest is the fact that if the expression of the reprogramming factors is silenced in the ‘zone of epigenetic instability’, the cells return back to being fibroblasts (Nagy & Nagy 2010). In (B), reprogramming factors have been introduced into an old senescent fibroblast (with SAHF represented by ‘dots’ in the nucleus) that has a low potential to age (y-axis) as it is already old. It then sets out on the path toward becoming an iPS cell. As it does so its epigenetic instability increases (x-axis) and passes through the ‘zone of epigenetic instability’. On reaching the ‘zone of epigenetic instability’, reprogramming factor expression is silenced and the cells return back to the fibroblast ‘ground-state’. In the diagram given, the fibroblast produced after passage through the ‘zone of epigenetic instability’ is a young fibroblast (with no SAHF) with a high potential to age. This is to be tested.