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3. Biomarkers of aging-associated chronic inflammation as a prognostic factor for human longevity

Author

Leposavić Gordana and Stojić-Vukanić Zorica

Subjects
longevity, low-grade chronic inflammation, non-communicable diseases, oxi-inflamm-aging, biomarkers of chronic inflammation, Pharmacy and materia medica, RS1-441
Abstract

It has been well-established that age-associated low-grade chronic inflammation contributes to the development of a spectrum of chronic diseases, including diabetes mellitus, ischemic heart disease, stroke, cancer, chronic kidney disease, non-alcoholic fatty liver disease and neurodegenerative diseases, which affect the quality of life of the elderly and influence their life span. This phenomenon is suggested to arise due to the weakening of the regulatory mechanisms of the immune response, and the persistence of exogenous and endogenous (reflecting oxidative cell injury) antigenic challenges, so it is referred to as oxi-inflamm-aging. Considering that the development of age-associated chronic inflammation is "silent", i.e., without clinical signs until the aforementioned complications become apparent, it is important to identify the biomarker(s) or pattern/cluster of biomarkers for this inflammation. It is also important to define new strategies to combat the "silent" damage induced by chronic inflammation. Given that at present there are no reliable biomarkers for chronic inflammation, this review points out the problems in defining biomarker(s) or patterns/clusters of biomarkers for chronic inflammation in order to stimulate further research and points to some possible routes of investigation.

Published
2022
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12. Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation.

Author

Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Ćuruvija, Ivana, Blagojević, Veljko, Dragačević, Luka, Kovačević, Ana, Kotur-Stevuljević, Jelena, and Leposavić, Gordana

Subjects
FLU vaccine efficacy, HUMORAL immunity, GERMINAL centers, ANTIBODY formation, VACCINE effectiveness
Abstract

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Biomarkers of aging-associated chronic inflammation as a prognostic factor for human longevity

Author

Leposavić, Gordana, Leposavić, Gordana, Stojić-Vukanić, Zorica, Leposavić, Gordana, Leposavić, Gordana, and Stojić-Vukanić, Zorica

Abstract

It has been well-established that age-associated low-grade chronic inflammation contributes to the development of a spectrum of chronic diseases, including diabetes mellitus, ischemic heart disease, stroke, cancer, chronic kidney disease, non-alcoholic fatty liver disease and neurodegenerative diseases, which affect the quality of life of the elderly and influence their life span. This phenomenon is suggested to arise due to the weakening of the regulatory mechanisms of the immune response, and the persistence of exogenous and endogenous (reflecting oxidative cell injury) antigenic challenges, so it is referred to as oxi-inflamm-aging. Considering that the development of age-associated chronic inflammation is “silent”, i.e., without clinical signs until the aforementioned complications become apparent, it is important to identify the biomarker(s) or pattern/cluster of biomarkers for this inflammation. It is also important to define new strategies to combat the “silent” damage induced by chronic inflammation. Given that at present there are no reliable biomarkers for chronic inflammation, this review points out the problems in defining biomarker(s) or patterns/clusters of biomarkers for chronic inflammation in order to stimulate further research and points to some possible routes of investigation., Činjenično je dobro argumentovano da hronična inflamacija niskog stepena koja se javlja u toku starenja ima važnu ulogu u razvoju čitavog spektra hroničnih bolesti, uključujući šećernu bolest, ishemijsku bolest srca, moždani udar, malignu bolest, hronično oštećenje bubrega, nealkoholnu masnu bolest jetre, neurodegenerativne i autoimunske bolesti, koje utiču na kvalitet i dužinu života starih osoba. Smatra se da ovaj fenomen nastaje kao rezultat slabljenja regulatornih mehanizama imunskog sistema i perzistentnog izlaganja organizma delovanju egzogenih i endogenih (generisanih oštećenjem ćelija oksidativnim stresom) antigenskih izazova, što se u literaturi opisuje terminom oksidativno-inflamatorno starenje. Imajući u vidu da se hronična inflamacija razvija klinički "nemo", odnosno da postaje manifestna tek kada se razviju prethodno pomenute komplikacije, jasno je koliko je važno identifikovati biomarker(e) ili obrasce/klastere biomarkera te inflamacije. S obzirom na to da u ovom trenutku nema pouzdanih markera hronične inflamacije, ovaj pregledni rad je tako koncipiran da ukaže na probleme u identifikaciji biomarkera ili obrazaca/klastera biomarkera hronične inflamacije, s ciljem da stimuliše dalja istraživanja, ali i da da smernice za buduća istraživanja.

Published
2022

26. Thymic changes as a contributing factor in the increased susceptibility of old Albino Oxford rats to EAE development

Author

Petrušić, Marija, Stojić-Vukanić, Zorica, Pilipović, Ivan, Kosec, Duško, Prijić, Ivana, Leposavić, Gordana, Petrušić, Marija, Stojić-Vukanić, Zorica, Pilipović, Ivan, Kosec, Duško, Prijić, Ivana, and Leposavić, Gordana

Abstract

The study was aimed to examine putative contribution of thymic involution to ageing-associated increase in susceptibility of Albino Oxford (AO) rats to the development of clinical EAE, and vice versa influence of the disease on the progression of thymic involution. To this end we examined (i) the parameters of thymocyte negative selection efficacy, the thymic generation of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and thymic capacity to instruct/predetermine IL-17-producing T-cell differentiation, and thymopietic efficacy-associated accumulation of “inflammescent” cytotoxic CD28- T cells in the periphery, and (ii) the key underlying mechanisms in young and old non-immunised AO rats and their counterparts immunised for EAE (on the 16th day post-immunisation when the disease in old rats reached the plateau) using flow cytometry analysis and/or RT-qPCR. It was found that thymic involution impairs: (i) the efficacy of negative selection (by affecting thymocyte expression of CD90, negative regulator of selection threshold and the expression of thymic stromal cell integrity factors) and (ii) Treg generation (by diminishing expression of cytokines supporting their differentiation/maturation). Additionally, the results suggest that thymic involution facilitates CD8+ T-cell differentiation into IL-17-producing cells (previously linked to the development of clinical EAE in old AO rats). Furthermore, they confirmed that ageing-related decrease in thymic T-cell output (as indicated by diminished frequency of recent thymic emigrants in peripheral blood) resulted in the accumulation of CD28- T cells in peripheral blood and, upon immunisation, in the target organ. On the other hand, the development of EAE (most likely by increasing circulatory levels of proinflammatory cytokines) contributed to the decline in thymic output of T cells, including Tregs, and thereby to the progression/maintenance of clinical EAE. Thus, in AO rats thymic involution via multi-layered mechanisms may fa

Published
2023

44. Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner

Author

Arsenović-Ranin Nevena, Nacka-Aleksić Mirjana, Đikić Jasmina, Perišić Milica, Kosec D., Pilipović I., Stojić-Vukanić Zorica, and Leposavić Gordana

Subjects
ovariectomy, thymic involution, thymocyte apoptosis, thymocyte proliferation, Veterinary medicine, SF600-1100
Abstract

The study was aimed to define the putative role of ovarian hormones in shaping thymocyte apoptosis and proliferation during thymic involution. Thymocytes from young adult and middle-aged rats ovariectomized (Ox) before puberty were examined for apoptosis and proliferation. Apoptosis and proliferation were measured in fresh thymocyte suspensions and in their 18-hour cultures, and fresh thymocyte suspensions, respectively. The thymocyte population and the major thymocyte subsets were analyzed following triple staining using anti-CD4 and anti-CD8 monoclonal antibodies and 7-AAD to label apoptotic or proliferating cells. The frequency of apoptotic cells was lower in thymocyte suspensions and cultures from Ox rats of both ages. This reflected in a diminished frequency of apoptotic cells amongst CD4+CD8+ double positive (DP) and CD4+CD8- single positive (SP), and DP cells in young and middle-aged Ox rats, respectively. Additionally, in thymocyte cultures from Ox rats the frequency of apoptotic cells amongst CD4+CD8- and CD4-CD8+ SP cells decreased with age, but increased within DP and CD4-CD8- double negative (DN) subsets, reaching in the former subset from middle-aged Ox rats higher values than in age-matched controls. The frequency of proliferating cells was also lower in Ox rats than in controls. This reflected the lower frequency of cycling cells amongst CD4+CD8- SP and CD4-CD8+ SP thymocytes in young rats, and DP and CD4-CD8+ SP thymocytes in middle-aged rats. Besides, in both SP and DP thymocyte subsets from Ox rats the frequency of proliferating cells declined with age. In conclusion, thymocyte apoptosis and proliferation exhibit ovarian hormone-dependent thymocyte subset specific alterations during thymic involution. [Projekat Ministarstva nauke Republike Srbije, br. 175050]

Published
2013
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45. Immunoreactive neuropeptides in the cells of human thymus

Author

Leposavić Gordana, Todorović Vera, Nikolić I., and Perisić Milica

Subjects
VIP, Substance P, CGRP, bombesin, motilin, human thymus, Biology (General), QH301-705.5
Abstract

The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall’s corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans.

Published
2011
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