NLRP3 inflammasome activity shifts toward regulating cell fate in aged macrophages

In aged bone marrow-derived macrophages, researchers investigated the functional remodeling of the NLRP3 inflammasome during aging. Upon stimulation with lipopolysaccharide, the cells did not show an increase in proinflammatory cytokine secretion. Instead, NLRP3 activation was accompanied by increased DNA fragmentation. Pharmacological inhibition of the inflammasome using MCC950 attenuated apoptosis, but it simultaneously increased the proportion of senescent cells. These results indicate a shift from apoptotic cell death toward cellular senescence. In aged macrophages, NLRP3 activity shifts away from a predominantly proinflammatory role to participating in the regulation of apoptosis, senescence, and cell survival.