| Literature DB >> 24093676 |
Yun-Hee Youm1, Ryan W Grant, Laura R McCabe, Diana C Albarado, Kim Yen Nguyen, Anthony Ravussin, Paul Pistell, Susan Newman, Renee Carter, Amanda Laque, Heike Münzberg, Clifford J Rosen, Donald K Ingram, J Michael Salbaum, Vishwa Deep Dixit.
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.Entities:
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Year: 2013 PMID： 24093676 PMCID： PMC4017327 DOI： 10.1016/j.cmet.2013.09.010
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287