Oxidative Stress Increases the Number of Stress Granules in Senescent Cells and Triggers a Rapid Decrease in p21waf1/cip1 Translation

Very little is known as to how the accumulation of senescent cells during aging may affect our ability to cope with various stresses. Here we show that the assembly of stress granules (SGs) is part of the early events used by senescent cells to respond to certain stresses. Although SGs can form in response to stress during senescence activation, their number significantly increases once the cells are fully senescent. This increase correlates with a rapid decrease in the expression levels of the cyclin kinase inhibitor p21, an important activator of senescence. Throughout stress, p21 mRNA is stabilized and localizes to SGs, but only during late senescence does this localization interferes with its translation. Additionally, we observed that when the stress is relieved, senescent cells produce lower levels of p21 protein, which correlates with a small delay in SG disassembly. Therefore, our data suggest that SG formation and the reduction in p21 protein levels represent two main events by which senescent cells respond to stress.