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Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and none of financial or personal interests appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunobiography describes the life-long effects of exogenous or endogenous stimuli on remodeling of immune cell biology, including the development of memory T and B-cells. The present study aimed at investigating the rhythms of changes in phenotypic features of memory T and B-cells along childhood and adolescence. A descriptive-observational investigation was conducted including 812 healthy volunteers, clustered into six consecutive age groups (9 Mths -1 Yr ; 2 Yrs ; 3-4 Yrs ; 5-7 Yrs ; 8-10 Yrs ; 11-18 Yrs ). Immunophenotypic analysis of memory T-cell (CD4 + and CD8 + ) and B-cell subsets were performed by flow cytometry. The results pointed out that memory-related biomarkers of T and B-cells displayed a bimodal profile along healthy childhood and adolescence, regardless of sex. The first stage of changes occurs around 2 Yrs , with predominance of naive cells, while the second and more prominent wave occurs around the age 8-10 Yrs , with the prevalence of memory phenotypes. The neighborhood connectivity profile analysis demonstrated that the number of correlations reaches a peak at 11-18 Yrs and lower values along the childhood. Males presented higher and conserved number of correlations when compared to females. Altogether, our results provide new insights into immunobiography and a better understanding of interactions among the cellular subsets studied here during childhood and adolescence., (© 2023. The Author(s).)

Background: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms., Methods: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay., Results: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54])., Conclusion: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality)., (Copyright © 2022 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Chronic bacterial infections are associated with changes in the immunosenescence process and immunological biomarkers can assist in monitoring these changes. The identification of this immunological profile is important because Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) infections are important factors of morbidity and mortality among the older adults. This study aimed to identify changes in the immunological profile in the presence of C. pneumoniae and H. pylori infections among community-dwelling older adults. This is a cross-sectional study that used data from 1432 participants from the Bambuí Cohort Study of Aging, Minas Gerais, Brazil. The presence of immunoglobulin G (IgG) for C. pneumoniae and H. pylori was considered a dependent variable and assessed in the participants' serum using the enzyme-linked immunosorbent assay (ELISA). In assessing the immunological profile, the following inflammatory markers were considered: CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1β, IL-6, IL-10, IL-12, TNF, and CRP. Associations were assessed by logistic regression, estimating odds ratios and confidence intervals (95%) using the Stata® V.13.1 software. The seroprevalence of anti-C. pneumoniae and anti-H. pylori antibodies was 55.9% and 70.3%, respectively. While high levels of anti-C. pneumoniae antibodies were associated with higher concentrations of CXCL10 and IL-10, higher levels of IL-1β and IL-6 were inversely associated with the titration of anti-H. pylori antibodies. The results characterize immunological profiles associated with these chronic infections and reinforce the potential effects of biomarkers on infections by these bacteria and on the immunosenescence process., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chronic infections can contribute to the aging process, but this issue is less studied in Latin America. The aim was to assess the prevalence and factors associated with cytomegalovirus (CMV), Herpes Simplex 1 (HSV-1), Chlamydia pneumoniae and Helicobacter pylori among the elderly. A total of 1,320 individuals participated from the baseline of the Elderly Cohort of Bambuí. IgG antibodies against infections and explanatory variables (sociodemographic factors, health behaviors and health conditions) were evaluated. Poisson regression models with robust variance were used. Seroprevalence rates were 99.4% for CMV, 96.7% for HSV-1, 56% for C. pneumoniae and 70.5% for H. pylori. Elderly men, women, smokers, diabetics, the disabled and those with high levels of IL-6 had a higher prevalence of CMV. HSV-1 was less frequent among women. The prevalence of C. pneumoniae was higher at ages >75 and among diabetics; it was lower among women and individuals with less schooling. H. pylori was less frequent among women and those with detectable levels of IL-1β, but more common among smokers. The findings show a high prevalence of chronic infection and a different epidemiologic profile for each pathogen, making it possible to detect groups that are vulnerable to these infections.

Chronic infections, such as cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), contribute to the inflammation process among older adults and are associated with the immunosenescence process. The aim was to identify the immunological profile associated with CMV and HSV-1 infections among older adults. This is a cross-sectional study, carried out with 1492 participants from the Bambuí Cohort Study of Aging - Minas Gerais, Brazil. For analysis purposes, we considered the presence of immunoglobulin G (IgG) for CMV and HSV-1 in the participants' serum, assessed by the enzyme-linked immunosorbent assay (ELISA); outcomes were defined by titration above the median (>160 UR/mL for HSV-1 and >399.5 U/mL for CMV). In order to assess the immunological profile, the following biomarkers were considered: IL-1beta, IL-10, IL-12, TNF, CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-6 and CRP; the first four being categorized as detectable levels or not, and the others using the Classification and Regression Tree (CART) method. The analysis was adjusted for sociodemographic variables, health behaviors and health conditions. The seroprevalence of anti CMV and anti HSV-1 antibodies was 99.4% and 97.0%, respectively. Higher concentrations of CXCL8 and CCL5 chemokines were associated with lower antibody titers for CMV, and higher concentrations of CXCL9, IL-6 and CRP were associated with higher levels of antibodies to CMV. Moreover, intermediate levels of CXCL10 were also associated with higher levels of antibodies to CMV. In HSV-1 infection, intermediate levels of CXCL9, CCL5 and IL-6 were less likely to have higher antibody titers for this infection. On the other hand, higher levels of CXCL10 and CRP were positively associated with higher antibody titers for HSV-1. The results describe important immunological changes and reinforce the potential effect of CMV and HSV-1 on the immunosenescence process., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to analyze the association between inflammatory markers and recurrent and severe falls in 1304 community-dwelling older adults from the Bambuí Cohort Study of Aging., Methods: Information about falls in the previous 12 months was collected, and classified based on recurrence (two or more falls) and severity (requirement of medical attention). The screened biomarkers included interleukins (IL-1β, IL-6, IL-10, and IL-12, TNF), chemokines (CXCL8, CXCL9, CXCL10, CCL2, and CCL5), and high-sensitive C-reactive protein (hs-PCR). Potential confounders included sociodemographic, behavioral, and health indicators. Associations were evaluated through logistic regression, using odds ratios (OR) and 95% confidence intervals (95% CI), with Stata 13.1., Results: The prevalence of recurrent and severe falls was 10.7% and 9.0%, respectively. After adjustments, elevated levels of IL-12 (OR: 1.92; 95% CI: 1.09-3.37) and CXCL9 (OR: 1.67; 95% CI: 1.05-2.66) were found to be associated with recurrent falls, while elevated levels of TNF (OR: 1.58; 95% CI: 1.01-2.50), IL-12 (OR: 2.04; 95% CI: 1.13-3.70), CXCL10 (OR: 1.75; 95% CI: 1.04-2.92), and CCL5 (OR: 1.90; 95% CI: 1.18-3.07) were associated with severe falls., Conclusions: The results highlight a wide range of biomarkers not yet explored in the literature and suggest that inflammation may be an important component of recurrent and severe falls., Competing Interests: Declaration of competing interest There is no conflict of interest in relation to the information presented in this manuscript. The authors are the sole responsible for the content and writing of this manuscript., (Published by Elsevier Inc.)

Objective: Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí., Methods: Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI)., Results: The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04-2.03), CCL5 (OR = 1.38, 95%CI 1.01-1.90) and CXCL9 (OR = 1.43, 95%CI 1.02-2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02-2.12) and three (OR = 2.08, 95%CI 1.12-3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively., Conclusions: Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.

The study aimed to identify the cutoff points for inflammatory markers that best discriminate the occurrence of metabolic syndrome in community-dwelling older adults. Baseline data were used from the elderly cohort in the city of Bambuí, Minas Gerais State, Brazil. The target exposure was presence of metabolic syndrome, defined according to the Adult Treatment Panel III criterion, and the outcomes included the following inflammatory markers: cytokines (IL-1β, IL-6, IL-10, IL-12 e TNF), chemokines (CXCL8, CXCL9, CCL2, CXCL10, and CCL5), and C-reactive protein (CRP). Definition of the cutoff points for the inflammatory markers was based on the Classification and Regression Tree (CART) method. The associations between these markers and metabolic syndrome were estimated by logistic regression models, obtaining odds ratios and 95% confidence intervals, considering adjustment for confounding factors. Prevalence of metabolic syndrome was 49.1%, and IL-1β, IL-12, and TNF levels were not associated statistically with this exposure. After adjustment, presence of metabolic syndrome was associated with higher IL-6 and CRP levels and lower CXCL8 and CCL5. Significant associations were also observed with intermediate serum CXCL9 and CXCL10 levels. The combination of markers also showed a significant and consistent association with metabolic syndrome. In addition to demonstrating an association between metabolic syndrome and a wide range of biomarkers (some not previously described in the literature), the results highlight that this association occurs at much lower levels than previously demonstrated, suggesting that metabolic syndrome plays an important role in the inflammatory profile of the older adults.

Introduction: Inflammation plays an important role in the aging process., Objective: This cross-sectional study aims to examine the association between inflammatory markers and hospitalizations among older adults, considering as potential confounding factors the predisposing and enabling factors for the use of health services and health conditions., Methods: We used data from 1,393 participants (≥ 60 years) in the baseline cohort from Bambuí. The markers assessed were ten cytokines and chemokines [interleukin (IL)-1, IL-6, IL-10, IL-12, tumor necrosis factor (TNF), CCL2, CCL5, CXCL8, CXCL9, and CXCL10]. The outcome variable was one or more hospitalizations in the preceding 12 months., Results: Elevated serum levels of IL-6 were significantly associated with hospitalizations [prevalence ratio (PR) = 1.38; confidence interval of 95% (95%CI) 1.02 - 1.87 and PR = 1.38; 95%CI 1.01 - 1.88 for the intermediate and highest tertiles, respectively]. High levels of CXCL9 were also independently associated with the outcome (PR = 1.38; 95%CI 1.01 - 1.89 and PR = 1.46; 95%CI 1.07 - 2.00, respectively). Other markers showed no statistically significant association with hospitalizations., Conclusion: Among the ten markers analyzed, only IL-6 and CXCL9 were associated with hospitalizations.

During immunosenescence many proinflammatory markers such as cytokines and chemokines are increased. This process called by Franceschi and colleagues as inflammaging is associated with chronic inflammation and the ethiology and pathophysiolgy of many ageing diseases as Alzheimer's and atherosclerosis. The knowledge of immune profile during ageing may provide some interventions that would improve the immune function in elderly and quality of life for old people. However, the identification of a group of potential biomarkers to monitor the ageing process is very difficult. In addition, most of the evidence evaluating immune biomarkers profile is based on data from older Caucasian adults. To our knowledge, no previous Latin American old population-based cohort has evaluated immunological parameters along the ageing process. The present work evaluated CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1, IL-6, IL-12, TNF and IL-10 serum levels in 1494 older adults aged 60 to 95 from a population based ageing cohort in Brazil. Our data suggest that there is an increased positive predicted probability of participants to be a high producer of IL-6, CXCL8 and CXCL9. Moreover, results did not differ between men and women, except for CXCL10 that increased only in men. Results were not different in the adjusted model by many potential confounders, including African genomic ancestry. Together, these findings add novel insights about the immunologic aspects of ageing supported by a large population-based cohort study that provides evidences that corroborate with the inflammaging proposal and subsidize the establishment of biomarkers for monitoring the health status of aged population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS])., Methods: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity., Results: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients., Conclusions: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.

Background: The ability of inflammatory markers to predict disability in later life has received growing attention. However, the current evidence came predominantly from Caucasians and the role of genomic ancestry has not been investigated., Objective: We investigated the prognostic value of multiple citokynes and chemokines for incident disability in admixed older Brazilians and whether genomic African and Native American ancestry affects the association., Design: Population-based longitudinal study., Setting: The Bambui-Epigen (Brazil) Cohort Study of Aging., Subjects: 1171 males and females aged ≥60 years over 15-year of follow-up., Methods: Outcome examined was incident activity of daily living (ADL) disability assessed annually (10,039 measures were performed). Serum levels of citokynes (IL6, IL12, TNF, IL10, and IL1β) and chemokines (CCL2, CCL5, CXCL8, CXCL9 and CXCL10) were measured at baseline. We used 370,539 Single Nucleotide Polymorphisms (SNPs) to estimate each individual genomic ancestry proportions. Potential confounding variables included a wide range of socio-demographic variables and health indicators. Statistical analyses were based on competing risk framework., Results: The incidence rate of disability was 57.9 per 1000 person-years. IL6 level at the highest quartile showed an independent association with ADL disability (SRH=1.32; 95% CI: 1.03, 1.70). Other inflammatory markers showed no statistically significant associations with the outcome. Neither genomic African nor Native American ancestry had an effect modifier on the associations (P for interaction >0.05 for all)., Conclusion: Among multi-inflammatory markers, only IL6 had the potential to identify people at increased risk of ADL disability, independently of ethno-racial background., (Copyright © 2017. Published by Elsevier B.V.)