Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.
Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.
复制标题
规范的NLRP3炎性体将系统性低级炎症与衰老功能下降联系起来。
DOI：
10.1016/j.cmet.2013.09.010
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发表时间：
2013-10-01
期刊：
影响因子：
29
通讯作者：
Dixit VD
中科院分区：
文献类型：
--
作者：
Youm YH;Grant RW;McCabe LR;Albarado DC;Nguyen KY;Ravussin A;Pistell P;Newman S;Carter R;Laque A;Münzberg H;Rosen CJ;Ingram DK;Salbaum JM;Dixit VD
尽管大量临床数据显示炎症与老年退行性疾病之间存在关联，但将全身炎症与衰老因果联系起来的免疫传感器仍不清楚。在这里，我们详细说明了Nlrp 3炎性体控制系统性低级别年龄相关的“无菌”炎症在外周和大脑独立的非经典的半胱天冬酶-11炎性体的机制。Nlrp 3炎性体的消融保护小鼠免受先天免疫激活、CNS转录组改变和星形胶质细胞增生中的年龄相关增加。与全身性低度炎症促进与年龄相关的退行性变化的假设一致，Nlrp 3炎性体缺陷介导的半胱天冬酶-1活性改善了血糖控制并减轻了骨丢失和胸腺死亡。值得注意的是，IL-1仅介导老年小鼠中认知功能和运动表现的Nlrp 3炎性体依赖性改善。这些研究揭示了Nlrp 3炎性体作为控制年龄相关炎症的上游靶标，并提供了降低Nlrp 3活性以延迟多种年龄相关慢性疾病的创新治疗策略。
Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related ‘sterile’ inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases.
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影响因子：
29
作者：
Chalkiadaki A;Guarente L
通讯作者：
Guarente L
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
9.1
作者：
Broderick, Lori;Gandhi, Chhavi;Mueller, James L.;Putnam, Christopher D.;Shayan, Katayoon;Giclas, Patricia C.;Peterson, Karin S.;Aceves, Seema S.;Sheets, Robert M.;Peterson, Bradley M.;Newbury, Robert O.;Hoffman, Hal M.;Bastian, John F.
通讯作者：
Bastian, John F.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Green DR;Galluzzi L;Kroemer G
通讯作者：
Kroemer G