MCC950 Suppresses Hepatic Inflammaging by Inhibiting NLRP3 Inflammasome Activation in Spontaneously Aged Mice

BACKGROUND: Aging is frequently accompanied by chronic, low-grade inflammation, often referred to as "inflammaging", which contributes to functional decline of multiple organs including the liver. The NLRP3 inflammasome has emerged as a key mediator of age-related inflammation; however, its pharmacological inhibition in the context of hepatic aging remains insufficiently explored. In this study, we investigated the effects of the selective NLRP3 inflammasome inhibitor MCC950 on inflammatory responses in the liver of aged mice. METHODS: Aged C57BL/6 mice (18 months old) were administered MCC950 intraperitoneally for four weeks, and liver tissues were analyzed for inflammatory and stress-related markers. RESULTS: MCC950 treatment significantly reduced hepatic expression of NLRP3, caspase-1 activation, and IL-1β production, accompanied by a decrease in proinflammatory cytokines such as p-STAT3. Histological analysis demonstrated attenuation of age-associated hepatic inflammatory infiltration and improved tissue architecture. Furthermore, MCC950 administration restored autophagy-related proteins (LC3B, p62) indicating broader protective effects on liver homeostasis. CONCLUSION: These findings suggest that NLRP3 inflammasome inhibition with MCC950 alleviates age-associated hepatic inflammation and may represent a potential therapeutic strategy for mitigating inflammaging and preserving liver function in the elderly.