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Monocytes present age-related changes in phospholipid concentration and decreased energy metabolism.
Aging Cell ( IF 8.0 ) Pub Date : 2020-02-27 , DOI: 10.1111/acel.13127 Mario Saare 1 , Liina Tserel 1 , Liis Haljasmägi 1 , Egon Taalberg 2 , Nadežda Peet 3 , Margus Eimre 3 , Rait Vetik 1 , Külli Kingo 4, 5 , Kai Saks 6 , Riin Tamm 7 , Lili Milani 8 , Kai Kisand 1 , Pärt Peterson 1
Aging Cell ( IF 8.0 ) Pub Date : 2020-02-27 , DOI: 10.1111/acel.13127 Mario Saare 1 , Liina Tserel 1 , Liis Haljasmägi 1 , Egon Taalberg 2 , Nadežda Peet 3 , Margus Eimre 3 , Rait Vetik 1 , Külli Kingo 4, 5 , Kai Saks 6 , Riin Tamm 7 , Lili Milani 8 , Kai Kisand 1 , Pärt Peterson 1
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Age‐related changes at the cellular level include the dysregulation of metabolic and signaling pathways. Analyses of blood leukocytes have revealed a set of alterations that collectively lower their ability to fight infections and resolve inflammation later in life. We studied the transcriptomic, epigenetic, and metabolomic profiles of monocytes extracted from younger adults and individuals over the age of 65 years to map major age‐dependent changes in their cellular physiology. We found that the monocytes from older persons displayed a decrease in the expression of ribosomal and mitochondrial protein genes and exhibited hypomethylation at the HLA class I locus. Additionally, we found elevated gene expression associated with cell motility, including the CX3CR1 and ARID5B genes, which have been associated with the development of atherosclerosis. Furthermore, the downregulation of two genes, PLA2G4B and ALOX15B, which belong to the arachidonic acid metabolism pathway involved in phosphatidylcholine conversion to anti‐inflammatory lipoxins, correlated with increased phosphatidylcholine content in monocytes from older individuals. We found age‐related changes in monocyte metabolic fitness, including reduced mitochondrial function and increased glycose consumption without the capacity to upregulate it during increased metabolic needs, and signs of increased oxidative stress and DNA damage. In conclusion, our results complement existing findings and elucidate the metabolic alterations that occur in monocytes during aging.
中文翻译：
单核细胞呈现出与年龄相关的磷脂浓度变化和能量代谢降低。
在细胞水平上与年龄有关的变化包括代谢和信号通路的失调。对血液白细胞的分析显示出一系列变化，这些变化共同降低了它们抵抗感染和解决生活中的炎症的能力。我们研究了从年轻成年人和65岁以上人群中提取的单核细胞的转录组学，表观遗传学和代谢组学谱图，以描绘其细胞生理学中主要的年龄依赖性变化。我们发现，来自老年人的单核细胞显示出核糖体和线粒体蛋白质基因表达的减少，并且在HLA I类基因座处表现出低甲基化。此外，我们发现与细胞运动相关的基因表达升高，包括CX3CR1和ARID5B基因与动脉粥样硬化的发展有关。此外，两个基因，的下调PLA2G4B和ALOX15B，属于参与磷脂酰胆碱转化为消炎的脂氧素的花生四烯酸代谢途径，与来自老年个体在单核细胞增加磷脂酰胆碱含量相关。我们发现与年龄有关的单核细胞代谢适应性变化，包括线粒体功能降低和糖类消耗增加，而在代谢需求增加期间却无能力上调糖代谢，以及氧化应激和DNA损伤增加的迹象。总之，我们的结果补充了现有发现，并阐明了衰老过程中单核细胞发生的代谢改变。
更新日期：2020-02-27
中文翻译：
单核细胞呈现出与年龄相关的磷脂浓度变化和能量代谢降低。
在细胞水平上与年龄有关的变化包括代谢和信号通路的失调。对血液白细胞的分析显示出一系列变化，这些变化共同降低了它们抵抗感染和解决生活中的炎症的能力。我们研究了从年轻成年人和65岁以上人群中提取的单核细胞的转录组学，表观遗传学和代谢组学谱图，以描绘其细胞生理学中主要的年龄依赖性变化。我们发现，来自老年人的单核细胞显示出核糖体和线粒体蛋白质基因表达的减少，并且在HLA I类基因座处表现出低甲基化。此外，我们发现与细胞运动相关的基因表达升高，包括CX3CR1和ARID5B基因与动脉粥样硬化的发展有关。此外，两个基因，的下调PLA2G4B和ALOX15B，属于参与磷脂酰胆碱转化为消炎的脂氧素的花生四烯酸代谢途径，与来自老年个体在单核细胞增加磷脂酰胆碱含量相关。我们发现与年龄有关的单核细胞代谢适应性变化，包括线粒体功能降低和糖类消耗增加，而在代谢需求增加期间却无能力上调糖代谢，以及氧化应激和DNA损伤增加的迹象。总之，我们的结果补充了现有发现，并阐明了衰老过程中单核细胞发生的代谢改变。
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