New implications of the inflammasomes in aging and age-related diseases
Mario D. Cordero
Institute of Nutrition and Food Technology "José Mataix Verdú", Department of Physiology, Biomedical Research Center, University of Granada, 18100 Granada, Spain. +34-958-241-000 (ext. 20316), Email: [email protected]
Abstract
Aging is the major risk factor for cardiovascular and many other chronic diseases. During this natural process, many alterations ocurr in the organism which are associated to the progressive impairment of several metabolic pathways related to body composition, insulin resistance, mitochondrial and autophagy dysfunction and inflammation. Since inhibition of low-grade chronic inflammation may provide health benefits, the role of NLRP3-inflammasome has been studied in metabolic and cardiovascular diseases. However, the implication of NLRP3-inflammasome in cardiac aging has been less studied. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate cardiac aging and improve healthspan. Ablation of NLRP3-inflammasome improved mice from age-related increased insulin sensitivity, showed 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 to atrial fibrillation by cardiovascular aging. Furthermore, aged NLRP3 knockout mice showed an inhibition of PI3K/AKT/mTOR pathway and autophagy improvement compared with old wild type mice. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart and preserved cardiac function and healthspan of aged mice.
Institute of Nutrition and Food Technology "José Mataix Verdú", Department of Physiology, Biomedical Research Center, University of Granada, 18100 Granada, Spain. +34-958-241-000 (ext. 20316), Email: [email protected]
Abstract
Aging is the major risk factor for cardiovascular and many other chronic diseases. During this natural process, many alterations ocurr in the organism which are associated to the progressive impairment of several metabolic pathways related to body composition, insulin resistance, mitochondrial and autophagy dysfunction and inflammation. Since inhibition of low-grade chronic inflammation may provide health benefits, the role of NLRP3-inflammasome has been studied in metabolic and cardiovascular diseases. However, the implication of NLRP3-inflammasome in cardiac aging has been less studied. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate cardiac aging and improve healthspan. Ablation of NLRP3-inflammasome improved mice from age-related increased insulin sensitivity, showed 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 to atrial fibrillation by cardiovascular aging. Furthermore, aged NLRP3 knockout mice showed an inhibition of PI3K/AKT/mTOR pathway and autophagy improvement compared with old wild type mice. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart and preserved cardiac function and healthspan of aged mice.
