Lack of the aryl hydrocarbon receptor accelerates aging in mice
Lack of the aryl hydrocarbon receptor accelerates aging in mice
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DOI：
10.1096/fj.201901333r
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发表时间：
2019-11-01
期刊：
影响因子：
4.8
通讯作者：
Moro, Maria A.
中科院分区：
文献类型：
--
作者：
Bravo-Ferrer, Isabel;Cuartero, Maria I.;Moro, Maria A.
芳烃受体（AhR）是一种配体激活的转录因子，主要以其在异生物质代谢和解毒中的作用以及其作为炎症调节剂的关键作用而闻名。在这里，我们比较了一组野生型和AhR基因敲除小鼠沿着衰老，以研究这种受体和年龄相关炎症之间的关系，称为“炎症”，在全身和中枢神经系统水平。我们的研究结果表明，AhR缺乏症与过早老化的表型，其特征在于早期炎症，如血浆细胞因子水平的增加所示。AhR的缺乏也促进了脑老化解剖特征的出现，例如白色物质完整性的丧失。此外，与年龄匹配的AhR（+）（/+）对照组相比，AhR（-/-）小鼠出现更早的空间记忆障碍和海马中星形胶质细胞增生增强。重要的是，我们发现AhR蛋白水平随着年龄的增长而下降，这强烈表明AhR与衰老之间的联系。
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as "inflammaging," both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR(-/-) mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when compared with their age-matched AhR(+)(/+) controls. Importantly, we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging.