School of Health Studies, University of Memphis, 38152, USA.
School of Health Studies, University of Memphis, 38152, USA; Center for Nutraceutical and Dietary Supplement Research, University of Memphis, Memphis, TN 38152, USA.
Mech Ageing Dev. 2019 Oct;183:111146. doi: 10.1016/j.mad.2019.111146. Epub 2019 Sep 4.
Inflammaging is the chronic low-grade inflammation that occurs with age that contributes to the pathology of age-related diseases. Monocytes are innate immune cells that become dysregulated with age and which can contribute to inflammaging. Metabolism plays a key role in determining immune cell functions, with anti-inflammatory cells primarily relying on fatty acid oxidation and pro-inflammatory cells primarily relying on glycolysis. It was recently shown that lipopolysaccharide (LPS)-stimulated monocytes can compensate for a lack of glucose by utilizing fatty acid oxidation. Given that mitochondrial function decreases with age, we hypothesized that classical monocytes taken from aged individuals would have an impaired ability to upregulate oxidative metabolism along with impaired effector functions. Aging did not impair LPS-induced oxygen consumption rate during glucose deprivation as measured on a Seahorse XFp system. Additionally, aged classical monocytes maintained inflammatory gene expression responses and phagocytic capacity during LPS stimulation in the absence of glucose. In conclusion, aged classical monocytes maintain effector and metabolic functions during glucose deprivation, at least in an ex vivo context.
衰老相关炎症是指随着年龄增长而发生的慢性低度炎症，它会导致与年龄相关疾病的发生。单核细胞是先天免疫细胞，随着年龄的增长而失调，可能会导致衰老相关炎症。代谢在决定免疫细胞功能方面起着关键作用，抗炎细胞主要依赖于脂肪酸氧化，而促炎细胞主要依赖于糖酵解。最近的研究表明，脂多糖（LPS）刺激的单核细胞可以通过利用脂肪酸氧化来弥补葡萄糖的缺乏。鉴于线粒体功能随着年龄的增长而下降，我们假设从老年人中提取的经典单核细胞在上调氧化代谢方面的能力会受到损害，同时效应功能也会受损。在 Seahorse XFp 系统上测量时，衰老并没有损害 LPS 诱导的葡萄糖剥夺期间的耗氧量。此外，在没有葡萄糖的情况下，衰老的经典单核细胞在 LPS 刺激期间维持炎症基因表达反应和吞噬能力。总之，在葡萄糖剥夺期间，衰老的经典单核细胞至少在体外环境中维持效应和代谢功能。
