Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence.
Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays Cell Senescence.
复制标题
Nrip1 的缺失可延长雌性小鼠的寿命、增强自噬并延缓细胞衰老。
DOI：
10.1093/gerona/glx257
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Yuan,Rong
中科院分区：
文献类型：
--
作者：
Wang,Jinyu;Chen,Xundi;Osland,Jared;Gerber,SkylerJ;Luan,Chao;Delfino,Kristin;Goodwin,Leslie;Yuan,Rong
使用女性性成熟年龄作为生物标志物，我们先前确定核受体相互作用蛋白1（Nrip1）作为可能调节衰老和长寿的候选基因。在目前的报告中，我们发现Nrip1的缺失可以显着延长雌性小鼠的寿命（对数秩检验，p= .0004）。我们还发现Nrip1的表达在衰老和饮食限制的不同组织中有不同的变化。值得注意的是，内脏白色脂肪组织（WAT）中Nrip1的表达随着年龄的增长而升高，但在饮食限制4个月后显著降低。然而，在腓肠肌，Nrip1的表达显着上调后，饮食限制。在小鼠胚胎成纤维细胞中，我们发现Nrip 1的缺失可以抑制成纤维细胞增殖，增强正常培养或氨基酸饥饿条件下的自噬，并延缓氧化和复制衰老。重要的是，在老年动物的WAT中，Nrip的缺失可以显著上调自噬，减少衰老细胞的数量。这些结果表明，删除Nrip1可以延长女性寿命，但组织特异性删除可能对健康寿命有不同的影响。WAT中Nrip1的缺失可能延缓WAT的衰老，延长健康寿命。
Using age of female sexual maturation as a biomarker, we previously identified nuclear receptor interacting protein 1 (Nrip1) as a candidate gene that may regulate aging and longevity. In the current report, we found that the deletion ofNrip1can significantly extend longevity of female mice (log-rank test,p= .0004). We also found thatNrip1expression is altered differently in various tissues during aging and under diet restriction. Remarkably,Nrip1expression is elevated with aging in visceral white adipose tissue (WAT), but significantly reduced after 4 months of diet restriction. However, in gastrocnemius muscle,Nrip1expression is significantly upregulated after the diet restriction. In mouse embryonic fibroblasts, we found that the deletion ofNrip1can suppress fibroblast proliferation, enhance autophagy under normal culture or amino acid starvation conditions, as well as delay oxidative and replicative senescence. Importantly, in WAT of old animals, the deletion of theNripcould significantly upregulate autophagy and reduce the number of senescent cells. These results suggest that deletingNrip1can extend female longevity, but tissue-specific deletion may have varying effects on health span. The deletion ofNrip1in WAT may delay senescence in WAT and extend health span.