Cell Metab. 31, 580–591 (2020)

Age-associated chronic inflammation has been dubbed ‘inflammaging’ and is linked to persistent activation of the NLRP3 inflammasome. In Cell Metabolism, He et al. show that NLRP3 is post-translationally modified by acetylation of conserved lysines located within the pyrin domain. Acetylated NLRP3 assembles more readily into active inflammasomes. The deacetylase SIRT2 negatively regulates NLRP3 activation. Accordingly, loss of SIRT2 enhances NLRP3–caspase 1 activation of proinflammatory interleukin (IL)-1β and IL-18. Expression of Sirt2 decreases in macrophages from older mice as compared to young mice, a finding correlated with increased NLRP3 and IL-1β activation. Older mice, especially SIRT2-deficient mice, have decreased glucose tolerance and insulin resistance — hallmarks of metabolic syndrome. These findings suggest that some effects of inflammaging are due to decreased SIRT2-mediated control of NLRP3 activation.