NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice
Metadatos
Afficher la notice complèteEditorial
Wiley
Materia
Autophagy Cardiac aging Longevity Morbidity Mortality
Date
2019Referencia bibliográfica
Marín‐Aguilar, F., Lechuga‐Vieco, A. V., Alcocer‐Gómez, E., Castejón‐Vega, B., Lucas, J., Garrido, C., ... & Ryffel, B. (2019). NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice. Aging Cell, e13050.
Patrocinador
Andalusian regional government; Consejería de Salud de la Junta de Andalucia, Grant/ Award Number: PI‐0036‐2014; Ministerio de economía y competitividad, Grant/Award Number: SAF2017‐84494‐C2‐1‐RRésumé
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 agedependent
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.