%L uneatlantico122
%P 1457-1464
%X The NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-related diseases in NLRP3-deficient mice. In this article, we determine whether, in old mice C57BL6J, the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age-related metabolic syndrome to providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. In addition, MCC950 inhibited the Pi3K/AKT/mTOR pathway, enhanced autophagy, and activated peroxisome proliferator-activated receptor-α in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by the mammalian target of rapamycin inhibition, thus activating autophagy and peroxisome proliferator-activated receptor-α. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-related metabolic syndrome.
%R doi:10.1093/gerona/glz239
%N 8
%K NLRP3 inflammasome; Aging; Autophagy; MCC950; PPARα.
%J The Journals of Gerontology: Series A
%A Rozalyn Anderson
%A Mario D. Cordero
%A Pedro Bullón
%A Jesús Ruiz-Cabello
%A Avril A B Robertson
%A Bernhard Ryffel
%A Antonio J Pérez-Pulido
%A Jordi Muntané
%A Mónica Pérez-Alegre
%A Eloísa Andújar-Pulido
%A Patricia de la Cruz
%A Matthew A Cooper
%A Debora Lendines-Cordero
%A Elísabet Alcocer-Gómez
%A Beatriz Castejón-Vega
%A Fabiola Marín-Aguilar
%V 75
%D 2019
%T NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity