NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice
NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice
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DOI：
10.1111/acel.13050
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发表时间：
2019-10-18
期刊：
影响因子：
7.8
通讯作者：
Cordero, Mario D.
中科院分区：
文献类型：
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作者：
Marin-Aguilar, Fabiola;Lechuga-Vieco, Ana V.;Cordero, Mario D.
虽然NLRP 3-炎性体与心血管疾病有关，但其在生理性心脏衰老中的作用在很大程度上是未知的。在衰老过程中，生物体中发生许多变化，这些变化与胰岛素抵抗、自噬功能障碍和炎症相关的代谢途径的进行性损害有关。在这里，我们研究了NLRP 3抑制可以减轻心脏衰老的分子机制。NLRP 3-炎性体的消融保护小鼠免受年龄相关的胰岛素敏感性增加，IGF-1和瘦素/脂联素比率水平降低，并减少心脏损伤，保护年龄依赖性PR间期的延长，这与心血管老化和端粒缩短减少引起的心房颤动相关。此外，与老年野生小鼠相比，老年NLRP 3 KO小鼠显示出PI 3 K/AKT/mTOR通路的抑制和自噬的改善，并保持了Nampt介导的NAD（+）水平，同时SIRT 1蛋白表达增加。这些发现表明，抑制NLRP 3可以防止心脏中许多与年龄相关的变化，保护老年小鼠的心脏功能并延长寿命。
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.