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Cell Metab. 2013 Oct 1;18(4):519-32. doi: 10.1016/j.cmet.2013.09.010.

Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.

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1
Pennington Biomedical Research Center, LSU System, Baton Rouge, LA 70808, USA.

Abstract

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.

PMID:
24093676
PMCID:
PMC4017327
DOI:
10.1016/j.cmet.2013.09.010
[Indexed for MEDLINE]
Free PMC Article

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