(A) SirT1 intervenes in the four category model of inflammation by modifying the output of inflammatory mediators in response to sensor activation, or of effector activity in response to secreted mediators. NR, other network regulators. (B) Recent investigations suggest that SirT1 may influence inflammation through multiple means. For example, it is reported to deactylate NFκB, encouraging exit from the nucleus. Additionally, it may deacetylate multiple histones and thus change chromatin accessibility in a gene-specific manner. Thus, a similar stimulus (in this case LPS binding to TLR4), can lead to a quantitatively or qualitatively different inflammatory outcome. By the same mechanism, a different effector response may result after cytokine stimulation.