A Mathematical Model of the Effects of Aging on Naive T Cell Populations and Diversity

et al. 2020

Preprint

It is widely well documented that ageing is accompanied by remodelling of the immune system including thymic atrophy and increased frequency of senescent T cells, thereby leading to immune compromise. The interaction of physical activity and the immune response is very complex and depends on the immune system status as well as the intensity, the type and the frequency of exercise. However, daily physical activity which particularly influences immunity and which declines dramatically with age, has not been widely reported in the studies. Therefore, this study was designed to explain whether physical activity sustained throughout life attenuates or reverses immunosenescence.The study subjects (n=99) were recruited from the University of the Third Age; they were assessed for the presence of chronic diseases and their functional capacity (6-min walking test) and cardiorespiratory (6-min Åstrand test) fitness were evaluated. Eventually, 54 subjects of the mean age >65 years participated in the study. The baseline peripheral naïve and memory T cells were analysed by flow cytometry in 34 elderly subjects who had maintained a high level of physical activity (Nordic-walking, Tai-Chi, cycling, 2-4 times per week) for much of their adult lives, and in 20 elderly people who had not been involved in regular exercise. The elderly who demonstrated a superior gait speed >1.3 m/s had a significantly higher the CD4+ naïve T lymphocyte population and a higher CD4+naïve/CD4+memory ratio compared to the inactive group. Above 50% of active individuals had the CD4/CD8 ratio ≥1 or ≤2.5 contrary to the inactive ones who demonstrated the values of CD4/CD8 ratio <1. Interestingly, the fat mass (FM) was positively correlated with CD4+ and CD4+memory in the inactive group which means that the number of CD4+memory cells and CD4+ T cells increased with the body fat content. Based on cytometry flow analysis, we concluded that major features of immunosenescence are contingent on lifestyle exercise in older adults.

Section: Introductionmentioning

confidence: 99%

Lifestyle Exercise Attenuates Immunosenescence; Flow Cytometry Analysis

et al. 2020

Preprint

“…The T cell pool is part of subpopulations of antigen-inexperienced naïve cells and antigen-experienced memory cells. The human immune compartment is composed of 10 12 T cells in total, ~10 11 of which are naïve [1]. During the process of ageing, the population of naïve T cells decreases, while the population of memory T cells undergoes intensive proliferation [2,3,4].…”

Section: Introductionmentioning

confidence: 99%

“…The remaining naïve T cell pool experiences a loss of T cell receptor (TCR) 'structural diversity' [5,6]. The appropriate range of antigen speci city is ensured by the diversity of T lymphocyte clones associated with a different number of TCR complexes [1]. Ageing affects naïve CD4 + T and CD8 + T cells counts in a different way.…”

Section: Introductionmentioning

confidence: 99%

Lifestyle Exercise Attenuates Immunosenescence; Flow Cytometry Analysis

et al. 2020

Preprint

Background: Interaction of physical activity and the immune response is very complex and depends on the intensity, duration and frequency of undertaken physical activity, the exposure to cytomegalovirus (CMV) infection and the age-related changes in the immune system. The daily physical activity, which particularly influences immunity, declines dramatically with age. Therefore, the aim of the study was to explain whether physical activity sustained throughout life can attenuate or reverse immunosenescenceMethods: Ninety-nine older adults (60-90 years) from the University of the Third Age were recruited for the study. According to the 6-min walk test (6WMT), the Åstrand-Ryhming bike test (VO2max) and Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire, the individuals were classified as physically active (n=34) and inactive (n=20) groups. The analysis of T lymphocytes between active vs. inactive was performed using eight-parameter CyFlow. Results: Analysis of the baseline peripheral naïve and memory T cells showed a significant relationship of lifestyle exercise with immunity risk profile (IRP) expressed by the CD4/CD8 ratio. Above 50% of physically active subjects demonstrated IRP ≥1 or ≤2.5 contrary to the inactive group who had IRP <1. The elderly with the result of 6WMT >1.3 m/s and VO2max >35 mL/kg/min had a significantly higher of CD4+ naïve T lymphocyte count and also a higher ratio of CD4+naïve/CD4+ memory. Interestingly, in active older adults with IgG CMV+ (n=30) the percentage of CD4+naïve T lymphocytes was higher than in the inactive group with IgG CMV+ (n=20).Conclusion: Based on the cytometry flow analysis, we concluded that lifestyle exercise could lead to rejuvenation of the immune system by increasing the naïve T cells count or by reducing the tendency of the inverse CD4/CD8 ratio.

“…The T cell pool is part of subpopulations of antigen-inexperienced naïve cells and antigen-experienced memory cells. The human immune compartment is composed of ~ 10 12 T cells in total, ~10 11 of which are naïve [3]. During the process of ageing, the population of naïve T cells decreases, while the population of memory T cells undergoes intensively proliferation, thereby reversing the balance of naïve and memory T cells that persisted at younger ages [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The remaining naïve pool of T cells experiences a loss of T cell receptor (TCR) 'structural diversity': the number of distinct TCR complexes present across the entire naïve pool [6,7]. The diversity of T cell lymphocyte clones, associated with the different number of distinct TCR complexes among the cell population, ensure the suitable range of antigen speci city [3].…”

Section: Introductionmentioning

confidence: 99%

Immunosenescence of Lymphocytes T and Implications for Age-Related Disorders

et al. 2020

Preprint

Background. The decrease in immunity with age is still a major health concern as elderly people are more susceptible to infections and increased incidence of autoimmunity. Consequently, there is an increasing interest in immunosenescence and changes in immunology cells like T cells. The aim of our study was to find a disproportion in subpopulation of T cells as well as CD4/CD8 ratio depending on the age, gender or comorbidities. Results. In the present study, a flow cytometry was used to indicate the differences between age, sex, disorders and fat content in the CD4+ and CD8+ T cells population divided into naïve and memory cells as well as CD4/CD8 ratio in people aged 71.9± 5.8 years (females n=83, males n=16) compared to young people aged 20.6 ± 1.1 years (females n=12, males n=19). The percentage of naïve CD4+ and CD8+ cells was found to be statistically significantly lower in the elderly compared to the young. In addition, gender was observed to play an important role in the outcomes in the analysed subpopulations and in female group, who live statistically longer than males, our older group of Polish women demonstrated a significantly higher percentage of naïve lymphocytes in both the CD4+ and CD8+ populations compared to men. The CD4/CD8 ratio increases with age, which can be considered one of the markers determining longevity. Elderly people with age-related diseases (hypertension) also show an increased level of CD4/CD8 ratio as well as CD4+. Conclusion. We demonstrated that changes in the T cells population, including naïve cell population as well as CD4/CD8 ratio, are important markers which can be predictive of healthy status. In order to accurately determine longevity, gender or age-associated diseases should be taken into account.