Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging
By Y. Youm, R. Grant, L. McCabe, Diana C. Albarado, K. Nguyen, A. Ravussin, P. Pistell, S. Newman, R. Carter, Amanda Laque and 5 more. Cell Metabolism, 2013
631 citations recorded by the source corpus.
SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical 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 innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.
Subfields: Biological Psychiatry, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/68d2d8833021f69949bff3f610add191f90a352f
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In Immunology
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Citations in the corpus
- Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “It responds to a wide range of cellular stress and is considered to contribute to the aging process and to age-related diseases (133).”
- The Mitochondrial Basis of Aging (2016, background): “Moreover, genetic ablation of Nlrp3 resulted in a diminished age-dependent activation of the innate immune system and protected animals from a number of age-related pathologies including bone loss, thymic involution, and loss of glycemic control (Youm et al., 2013).”
- Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. (2014, background): “In a mouse model, reduction in the Nlrp3 inflammasome-dependent proinflammatory cascade attenuated age-related degenerative changes across multiple organs (39).”