Monocytes present age‐related changes in phospholipid concentration and decreased energy metabolism

• Published in: Aging cell Vol. 19; no. 4; pp. e13127 - n/a
• Main Authors: Saare, Mario, Tserel, Liina, Haljasmägi, Liis, Taalberg, Egon, Peet, Nadežda, Eimre, Margus, Vetik, Rait, Kingo, Külli, Saks, Kai, Tamm, Riin, Milani, Lili, Kisand, Kai, Peterson, Pärt
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2020; John Wiley and Sons Inc
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aging; Arachidonic acid; Arteriosclerosis; Cellular Senescence; CX3CR1 protein; Development and progression; DNA damage; DNA methylation; Energy Metabolism; Epigenetic inheritance; Epigenetics; Gene expression; Genes; glucose metabolism; Health aspects; Histocompatibility antigen HLA; Humans; Inflammation; Lecithin; Leukocytes; Metabolism; Metabolomics; Mitochondria; Monocytes; Monocytes - metabolism; Older people; Original; Oxidative stress; Phosphatidylcholine; phosphatidylcholines; Phospholipids; Phospholipids - metabolism; transcriptome; Unsaturated fatty acids; DNA methylation; monocytes; phosphatidylcholines; aging; glucose metabolism; transcriptome
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13127

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. We find age‐related changes in monocyte metabolic fitness, including increased glucose consumption without the capacity to upregulate it during increased metabolic needs, and reduced mitochondrial function together with signs of increased oxidative stress and DNA damage. Downregulation of PLA2G4B and ALOX15B expression correlates with increased phosphatidylcholine content in monocytes from older individuals and possibly lower synthesis of anti‐inflammatory lipoxins.