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

Autor(es)

Cotrim Guerreiro da Silva, Ismael Dale ^[1] ; Lobo Marchioni, Dirce Maria ^[2] ; Ferreira Carioca, Antonio Augusto ^{[3, 2]} ; Bueno, Valquiria ^[4] ; Braga Colleoni, Gisele Wally ^[5]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Gynecol, Escola Paulista Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Publ Hlth, Nutr Dept, Sch Med FMUSP, Sao Paulo - Brazil

^[3] Univ Fortaleza UNIFOR, Nutr Dept, Fortaleza, Ceara - Brazil

^[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Dept Clin & Expt Oncol, Escola Paulista Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: IMMUNITY & AGEING; v. 18, n. 1 AUG 13 2021.
• Citações Web of Science: 0

Resumo

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 Sao 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. (AU)

• Processo FAPESP: 17/21801-2 - Preditores de gravidade e novos tratamentos para neoplasias da medula óssea
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático