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Restoration of senescent human diploid fibroblasts by modulation of extracellular matrix
Hae Ri Choi, Kyung a Cho, Hyun Tae Kang, Jung Bin Lee, Matt Kaeberlein, Yousin Suh, In Kwon Chung and Sang Chul Park
Aging Cell 2011, 10, ppp148-157 (doi:10.1111/j.1474-9726.2010.00654.x)

Thoughts/Implications/Summary
Cells not expressing telomerase eventually begin to show evidence of a DNA damage response (DDR) resulting in terminal arrest of the cell cycle limiting further replication. This replication limit is known as the 'Hayflick' limit. Senescence is the upshot of reaching the Hayflick limit and senescence is associated with phenotypic traits including an increase in senescence associated β galactosidase staining, increase in intracellular reactive oxygen species (ROS), decrease in BrdU staining, decreased response to apoptotic signals, and decreased response to epidermal growth factor (EGF). Additional markers include sets of secretory proteins, structural changes in nuclear lamina, and gamma-H2AX staining on uncapped telomeres. It is thought that the senescent state is one that is, for the most part, irreversible. However, previously a study by Conboy, et al. provided evidence that it may be possible to restore old (and, possibly, senescent) cells to a more youthful state[1]. The mechanism mediating a reversion from a senescent state to a more youthful state could be contingent on the microenvironment which is composed of the extracellular matrix (ECM). Building on previous observations the authors sought to test the idea that old (i.e., senescent) cells that have reached their replication limit can be restored to a more youthful state.

Slow stochastic transgene repression with properties of a timer
Clifford L Wang, Desiree C Yang and Matthias Wabl
Genome Biology 2006, 7:R47 (doi:10.1186/gb-2006-7-6-r47)

Thoughts/Implications/Summary
The ability to identify clonal populations exhibiting predictable repression kinetics is intriguing. This finding has implications in the context of retroviral-mediated gene therapy. In this paper the location of integration was associated with the decay kinetics observed. This phenomenon is most likely cell-type/individual dependent. It may be possible to screen cells during retroviral-mediated gene therapy for the kinetics of transgene repression and identify those cells bearing an integration event at a genomic position allowing for predictable/reproducible expression kinetics and selection of clones with a low probability of tumorigenicity. One could envision a scenario where cells are isolated from an individual, "corrected" by way of retroviral integration of the functional gene in question, clonal populations of cells are identified that exhibit predictable expression/repression kinetics with subsequent use of these cells to treat the individual. If in vitro expression/repression kinetics are exhibited in vivo then one could tailor a treatment plan based on these kinetics. (That is assuming that repression is an issue of concern in individuals undergoing gene therapeutic modalities to treat the disease in question. I am ignorant of the long-term prognoses of individuals undergoing these treatments...) As an aside, one could also monitor these cells for things such as aneuploidy.