Immunosenescence and gender: a study in healthy Cubans

Verdecia, Beatriz García; Saavedra, Danay; Lorenzo-Luaces, Patricia; Alvarez, Teresita de Jesús Badía; Rupalé, Idrissa Leonard; Herrera, Zaima Mazorra; Ramos, Tania Crombet; Dávila, Antonio

doi:10.1186/1742-4933-10-16

Cited by 22 publications

(21 citation statements)

References 58 publications

(68 reference statements)

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“…T cells are presumed to follow a certain surface-marker differentiation, first losing CD45RA expression, then CCR7 (or CD62L), and finally regaining CD45RA (57). 11 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) ns (***)…”

Section: Original Articlementioning

confidence: 99%

“…Several studies have reported age‐dependent cellular changes to the immune system, for example, changes in number and function of innate immune cells subsets as well as subsets of the adaptive immune system . Age associated changes are most pronounced for the adaptive immune cell subsets.…”

mentioning

confidence: 99%

“…In addition to immunosenescence, an increase of several proinflammatory cytokines such as IL-6 and TNF-a is observed in the elderly (11). This opposing process is termed inflammaging and is characterized as a chronic state of unspecific low-grade inflammatory activity linked to the occurrence of autoimmune disease and atherosclerosis (12,13) Several studies have reported age-dependent cellular changes to the immune system, for example, changes in number and function of innate immune cells subsets as well as subsets of the adaptive immune system (4,(14)(15)(16)(17)(18)(19)(20)(21)(22). Age associated changes are most pronounced for the adaptive immune cell subsets.…”

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confidence: 99%

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Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

et al. 2016

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Flow cytometry is now accepted as an ideal technology to reveal changes in immune cell composition and function. However, it is also an error-prone and variable technology, which makes it difficult to reproduce findings across laboratories. We have recently developed a strategy to standardize whole blood flow cytometry. The performance of our protocols was challenged here by profiling samples from healthy volunteers to reveal age-and gender-dependent differences and to establish a standardized reference cohort for use in clinical trials. Whole blood samples from two different cohorts were analyzed (first cohort: n 5 52, second cohort: n 5 46, both 20-84 years with equal gender distribution). The second cohort was run as a validation cohort by a different operator. The "ONE Study" panels were applied to analyze expression of >30 different surface markers to enumerate proportional and absolute numbers of >50 leucocyte subsets. Indeed, analysis of the first cohort revealed significant age-dependent changes in subsets e.g. increased activated and differentiated CD4 1 and CD8 1 T cell subsets, acquisition of a memory phenotype for Tregs as well as decreased MDC2 and Marginal Zone B cells. Males and females showed different dynamics in age-dependent T cell activation and differentiation, indicating faster immunosenescence in males. Importantly, although both cohorts consisted of a small sample size, our standardized approach enabled validation of age-dependent changes with the second cohort. Thus, we have proven the utility of our strategy and generated reproducible reference ranges accounting for age-and gender-dependent differences, which are crucial for a better patient monitoring and individualized therapy. V C 2016 International Society for Advancement of Cytometry

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Section: Original Articlementioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

et al. 2016

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“…These interactions allow cross-communication between different cell types, at different hierarchical levels, translating environmental signals into molecular signals (2,7). The pro-inflammatory profile becomes strategic throughout the lifespan (8)(9)(10)(11) -an increase of cytokine secretion, also thought to be associated with the influence of CMV-infection, may be at least partly responsible for age-associated degenerative disorders (12)(13)(14)(15)(16). Previous studies usually investigated individual roles of different cytokines, inflammatory mediators or metabolic factors in the age-related physiological alterations (17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

Benedetto

Müller

Rauskolb

et al. 2019

Preprint

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Background: Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins' metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro-and antiinflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them. Results: In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination (R 2 ) that was calculated for all possible pairs of variables (N = 33) in four groups (CMVmen and women; CMV + men and women). Network topology has been evaluated by clustering coefficient (CC) and characteristic path length (CPL) as well as local (Elocal) and global (Eglobal) efficiency, showing the degree of network segregation (CC and Elocal) and integration (CPL and Eglobal). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC, as well as local and global efficiency were highest and CPL shortest in CMVmales (having lowest inflammatory status and highest cognitive performance). CMVand CMV + females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q-value ranged between 0.397 and 0.453). Conclusions: In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro-and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.

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“…It is well documented that with decrease in age naïve CD8 + T cells, highly differentiated CD8 + T cells lacking CD28 accumulate and those CD8 + CD28 − T cells upregulate the expression of CD45RA. Additionally, these cells show signs of replicative senescence such as a decreased proliferation ability, shortened telomeres, impairment of telomerase activity, and upregulation of CD57 ( 3 , 4 ). These facts have been frequently associated with chronic CMV infection ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

T Cell Subpopulations in Healthy Elderly and Lung Cancer Patients: Insights from Cuban Studies

2017

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The senescence of the immune system and the risk of cancer increase with aging. Age itself entails changes in the immune system, which are related to a decrease in thymic output of naïve lymphocytes, an accumulation of chronic antigenic load, notably chronic viral infections such as cytomegalovirus (CMV), and replicative senescence of lymphocytes. These changes could eventually contribute to cancer risk and affect the response to cancer treatment. However, several confounding factors make it difficult to draw a picture of causal relationships. Studies in diverse human populations could contribute to clarify these complex relationships. Here, we summarize the current knowledge about the senescence of the T cells, the relationship with CMV infection, cancer, and cancer treatment. We also review the results of a series of studies performed in Cuba whose population is characterized by the unusual combination of long life expectancy and high antigenic load, including high seroprevalence of CMV, typical of tropical countries. Although immunosenescence affects almost all components and functions of the immune response, its most salient feature is a decrease in numbers and proportions of naïve CD8+ T lymphocytes and an accretion of terminally differentiated CD8+ T lymphocytes. These features were confirmed by the Cuban studies, but interestingly a clear gender effect also appeared. Moreover, as aging is a global phenomenon, a fast increase in elderly with malignancies is expected; therefore, the evaluation of patient’s immune status would support the decision of treating them with immunotherapy and predict the efficacy of such treatments, thereby improving benefits for the patients.

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Immunosenescence and gender: a study in healthy Cubans

Cited by 22 publications

References 58 publications

Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

Age and gender leucocytes variances and references values generated using the standardized ONE‐Study protocol

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

T Cell Subpopulations in Healthy Elderly and Lung Cancer Patients: Insights from Cuban Studies

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