Departamento de Farmacología y Toxicología, Facultad de Medicina, Madrid, Spain.
Instituto Universitario de Investigación en Neuroquímica (IUIN), Madrid, Spain.
FASEB J. 2019 Nov;33(11):12644-12654. doi: 10.1096/fj.201901333R. Epub 2019 Sep 4.
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.-Bravo-Ferrer, I., Cuartero, M. I., Medina, V., Ahedo-Quero, D., Peña-Martínez, C., Pérez-Ruíz, A., Fernández-Valle, M. E., Hernández-Sánchez, C., Fernández-Salguero, P. M., Lizasoain, I., Moro, M. A. Lack of the aryl hydrocarbon receptor accelerates aging in mice.
芳香烃受体 (AhR) 是一种配体激活的转录因子，主要因其在异生物质代谢和解毒中的作用以及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 缺失小鼠随年龄增长的情况，以研究该受体与称为“炎症衰老”的年龄相关炎症之间的关系，这在系统和中枢神经系统 (CNS) 水平上都有研究。我们的结果表明，AhR 缺乏与过早衰老表型有关，表现为炎症衰老的早期表现，如血浆细胞因子水平升高。AhR 的缺失还促进了脑衰老的解剖特征的出现，例如白质完整性的丧失。此外，与同龄的 AhR 对照相比，AhR 小鼠表现出更早的空间记忆障碍和海马中的星形胶质细胞增生增强。重要的是，我们发现 AhR 蛋白水平在该脑结构中随年龄增长而下降，这强烈表明 AhR 与衰老之间存在联系。
