Sustained activation of NLRP3 inflammasome contributes to delayed wound healing in aged mice

The cutaneous wounds in the elderly heal poorly, resulting in medical and economic burdens posed by defect repairing. Age-related delayed wound healing is associated with persistent inflammation and insufficient ECM deposition. The NLRP3 inflammasome has been proven to be a critical regulator of age-related inflammatory diseases, as well as impaired wound healing. Here, we create a 6 mm full-thickness cutaneous wound on the back of young and aged mice. Compared with young mice, aged counterparts display a retardation in wound healing, accompanied by increased activation of NLRP3 inflammasome. The application of the NLRP3 inhibitor (MCC950) ameliorates wound healing in aged mice. MCC950 inhibits sustained inflammation and reduces pyroptotic cell death in fibroblasts by blocking the abnormal activation of the NLRP3 inflammasome. Our findings illuminate that the NLRP3 inflammasome is a previously unrecognized regulator of aged wound healing and may be a potential target for the therapeutic strategy of delayed wound healing with aging.

Automated summary

Cutaneous wounds in the elderly heal poorly due to persistent inflammation and insufficient ECM deposition. The NLRP3 inflammasome plays a critical role in age-related inflammatory diseases and impaired wound healing. In this study, the activation of NLRP3 inflammasome was found to be increased in aged mice, causing a delay in wound healing. The application of NLRP3 inhibitor (MCC950) improved wound healing in aged mice by reducing inflammation and cell death.