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NLRP3-inflammasome suppression improves longevity and prevents cardiac aging in mice

ABSTRACT: Aging is the major risk factor for cardiovascular and many other chronic diseases. During this natural process, many alterations occur in the organism which are associated with progressive impairment of several metabolic pathways related to body composition, insulin resistance, mitochondrial and autophagy dysfunction and inflammation. Recently, the role of NLRP3 inflammasome has been studied in cardiovascular diseases showing its implication in the pathological progression of atherosclerosis, heart failure, and hypertension. However, the role of the NLRP3 inflammasome in cardiac aging has been less well studied. Herein, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3 inflammasome increased lifespan and protected mice from age-related increased insulin sensitivity, reduced IGF-1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of age–dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging. Furthermore, old NLRP3 KO mice showed an inhibition of PI3K/AKT/mTOR pathway and autophagy improvement compared with old wild type mice and preserved Nampt-mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart and preserved cardiac function of aged mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE124483 | GEO | 2019/10/01

REPOSITORIES: GEO

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