Ordinary somatic cells can be reprogrammed into a state similar to that of embryonic stem cells, and the results are known as induced pluripotent stem cells (iPSCs). These can in theory be used to generate any type of cell, once a specific recipe of signals and environment is established for that cell type. One goal is to generate sources of patient-matched cells to order so as to facilitate regenerative therapies, but at this stage it is just as important to be able to generate cells for research - to build useful models of specific age-related and genetic conditions and thus rigorously investigate the underlying biochemistry.
It has been established that some properties exhibited by cells in old tissue are removed or lessened by the process of generating IPSCs. This is most interesting and probably a bonus when it comes to use in therapies, but quite inconvenient if your interest lies in building models of age-related or genetic conditions, as some of the basis for the condition is stripped out by the process of generating the cells that you want to use. Here is a discussion on this topic, in which researchers involved in studying Hutchinson-Gilford progeria syndrome (HGPS) seek ways to "re-age" the cells they are work with:
Age is the most important risk factor in many late-onset disorders such as Parkinson's disease (PD) as illustrated by the fact that PD patients do not develop symptoms until later in life. Therefore, it is imperative to consider age as well as genetic mutations when attempting to model these diseases in vitro.
Previously, it was unclear whether a donor cell from an old individual would maintain its age-associated properties following conversion into other cell fates ex vivo. However, recent studies have presented evidence that markers of cellular age, including mitochondrial fitness and telomere length, are reset to a young-like state when old donor fibroblasts are reprogrammed to iPSCs.
Indeed, our own study defines a broad set of age-associated markers, and we demonstrate the rejuvenation of old donor fibroblasts based on those markers. The corresponding iPSCs derived from old donors no longer exhibit features that distinguish old from young primary cells including abnormal nuclear morphologies, accumulated DNA damage, increased reactive oxygen specifies (ROS), reduced levels of a set of nuclear organization proteins, and loss of heterochromatin markers. We could not be sure, however, whether pluripotency simply suppresses "age" by downregulating age-related proteins such as progerin. Indeed HGPS iPSCs also show a loss of the age-associated markers at the pluripotency stage.
Therefore, iPSCs were differentiated into a fibroblast-like cell in order to match the phenotype of the donor fibroblasts used for reprogramming. We were able to show that similar to the pluripotency stage, iPSC-derived fibroblasts from old donors appear "young", suggesting that the cell's intrinsic molecular clock is reset following the reprogramming step. In contrast, HGPS iPSC-derived fibroblasts quickly upregulate progerin (the disease-causing protein) during differentiation, resulting in the re-induction of age-associated phenotypes. Based on these findings we hypothesized then that the difficulties of modeling late-onset disease in differentiated iPSCs could be caused by the fact that they are too "young" and that the implementation of defined genetic cues such as progerin overexpression may be sufficient to reintroduce age-associated markers.