Functional Shift of NLRP3 Inflammasome Activity in Aged Macrophages

The present study investigates the functional remodeling of the NLRP3 inflammasome in bone marrow-derived macrophages during aging. Upon LPS stimulation, no increase in proinflammatory cytokine secretion was detected; however, NLRP3 activation was accompanied by an increase in DNA fragmentation. Pharmacological inhibition of the inflammasome with MCC950 attenuated apoptosis while simultaneously increasing the proportion of senescent cells, indicating a shift from apoptosis toward senescence. These findings suggest a functional shift in NLRP3 activity during aging: rather than playing a predominantly proinflammatory role, it participates in the regulation of the balance between apoptosis, senescence, and cell survival. This highlights the need for a cautious approach to the therapeutic inhibition of NLRP3 in age-associated pathologies.