Exploring the potential role of the aging macrophage in response to Francisella infections is a current area of investigation in our laboratory. The onset of cell death and subsequent hypercytokinemia are both hallmarks of the acute onset of severe sepsis associated with Francisella infections. Normally in young mice infected with Francisella, cell death is widespread initially at 3 DPI and continues to worsen with time post infection until death. TUNEL staining in these mice appears confluent, especially around blood vessels and highlighting large foci of necrotic infiltrates that have been shown to be rich sources of damage associated molecular patterns that can potentially further exacerbate host mediated tissue destruction. However, one observation we made in the aged mice was an increase in TUNEL staining initially in aged mice at 1 DPI. Notably, the pattern at this time point is confined to individual aggregates or cells in the lung. It could be hypothesized that the initial increase in apoptotic cells could be a more controlled response that allows for the apoptotic debris to be taken up more efficiently. We also found that both pro and anti-inflammatory cytokines were highly upregulated at 3 DPI and 5 DPI in young mice as is consistent with hypercytokinemia associated with severe sepsis. However, the response in aged mice appeared to be blunted. At day 3 post infection, mice could be separated based on their bacterial burdens and pulmonary cytokine expression into either slow progressors or potential aged survivors and those which were more likely to succumb to infection within the normal time frame. Cell death and hypercytokinemia were strikingly absent or reduced in mice that were deemed potential survivors. Further studies are necessary to dissect immune parameters associated with survival. In summary aged mice displayed an attenuated response to respiratory F. novicida infections. This included a reduction in lung bacterial burden early in the infection. In general, aged mice also displayed a less vigorous pulmonary cytokine response with aged survivors showing an even further reduction in production of pulmonary cytokines. Studies are ongoing to determine potential differences in kinetics, distribution and function of distinct leukocyte subsets in infected lungs of young and aged mice. UBF is acetylated in S and G2 phase and is deacetylated in mitosis and early G1. For Axitinib acetylation of UBF, CBP and Rb-HDAC are key regulators which function in a “flip-flop” manner. It has been found that acetylation and deacetylation regulate UBF activity without affecting its DNA binding properties. Instead, UBF acetylation activates Pol I transcription by enhancing the association between UBF and Pol I components.