May critical molecular cross-talk between indoleamine 2,3-dioxygenase (IDO) and arginase during human aging be targets for immunosenescence control?

Background This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any...

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Published in:Immunity & ageing 2021-08, Vol.18 (1), p.1-33, Article 33
Main Authors: da Silva, Ismael Dale Cotrim Guerreiro, Marchioni, Dirce Maria Lobo, Carioca, Antonio Augusto Ferreira, Bueno, Valquiria, Colleoni, Gisele Wally Braga
Format: Article
Language:English
Subjects:
Age
Aging
Amino acids
Arginase
Biomarkers
Dendritic cells
Discriminant analysis
Fatty acids
Glycerol
Health surveys
Hyperactivity
Hypotheses
IDO
Immune system
Immunosenescence
Ionization
Life sciences
Lymphocytes T
Macrophages
Mass spectrometry
Mass spectroscopy
Measurement techniques
Metabolism
Metabolites
Methylation
Oxidation
Peripheral blood
Phenotyping
Plasma
Population
Scientific imaging
Senescence
Suppressor cells
T cells
Tryptophan 2,3-dioxygenase
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Summary:Background This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any eventual perturbed biochemical pathway by the aging process in prospectively collected peripheral blood plasma from 166 individuals representing the population of São Paulo city, Brazil. Results Indoleamine 2,3-dioxygenase (IDO) activity (Kyn/Trp) was significantly elevated with age, and among metabolites most associated with elevations in IDO, one of the strongest correlations was with arginase (Orn/Arg), which could also facilitate the senescence process of the immune system. Hyperactivity of IDO was also found to correlate with increased blood concentrations of medium-chain acylcarnitines, suggesting that deficiencies in beta-oxidation may also be involved in the immunosenescence process. Finally, our study provided evidence that the systemic methylation status was significantly increased and positively correlated to IDO activity. Conclusions In the present article, besides identifying elevated IDO activity exhibiting striking parallel association with the aging process, we additionally identified increased arginase activity as an underlying biochemical disturbance closely following elevations in IDO. Our findings support interventions to reduce IDO or arginase activities in an attempt to preserve the functionality of the immune system, including modulation of myeloid-derived suppressor cells (MDSCs), T cells, macrophages, and dendritic cells' function, in old individuals/patients. Keywords: IDO, Arginase, Aging, Senescence, Immune system
ISSN:1742-4933
1742-4933
DOI:10.1186/s12979-021-00244-x