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.
