Open AccessMonocytes present age‐related changes in phospholipid concentration and decreased energy metabolism
Author(s) -
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
Publication year - 2020
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13127
Subject(s) - biology , downregulation and upregulation , transcriptome , inflammation , oxidative stress , lipid metabolism , arachidonic acid , epigenetics , endocrinology , gene expression , gene , medicine , immunology , biochemistry , enzyme
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.