期刊
CELL METABOLISM
卷 18, 期 4, 页码 519-532出版社
CELL PRESS
DOI: 10.1016/j.cmet.2013.09.010
关键词
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资金
- US National Institutes of Health (NIH) [AG043608, AI105097, DK090556]
- Pennington Foundation
- NIH [P20 RR02195, HD055528]
- Pennington Center of Biomedical Research Excellence [NIH 8P20 GM103528]
- Nutrition and Obesity Research Center [NIH P30 DK072476]
Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in the elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism by which the Nlrp3 inflammasome controls systemic low-grade age-related sterile'' inflammation in both periphery and brain independently of the noncanonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome, and astrogliosis. Consistent with the hypothesis that systemic low-grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome-mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome-dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer an innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.
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