2026-06-14T03:37:45Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/93272024-10-31T11:39:39Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Marín-Aguilar, Fabiola author Lechuga-Vieco, Ana V. author Alcocer-Gómez, Elísabet author Castejón-Vega, Beatriz author Lucas, Javier author Garrido, Carlos author Peralta-Garcia, Alejandro author Pérez-Pulido, Antonio J author Varela-López, Alfonso author Quiles, José L author Ryffel, Bernhard author Flores, Ignacio author Bullón, Pedro author Ruiz-Cabello, Jesus author Cordero, Mario D author 2020-01 While NLRP3-inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3-inflammasome 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 the age-dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild 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, preserved cardiac function of aged mice and increased lifespan. Aging Cell. 2020; 19(1):e13050 10.1111/acel.13050 1474-9726 1474-9718 Aging cell 31625260 http://hdl.handle.net/20.500.12105/9327 NLRP3-inflammasome Autophagy Cardiac aging Longevity Morbidity Mortality NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice