Pre-Existing Hypertension Is Related with Disproportions in T-Lymphocytes in Older Age

Age-related immune deficiencies increase the risk of comorbidities and mortality. This study evaluated immunosenescence patterns by flow cytometry of naïve and memory T cell subpopulations and the immune risk profile (IRP), expressed as the CD4/CD8 ratio and IgG CMV related to comorbidities. The disproportions in naïve and memory T cells, as well as in the CD4/CD8 ratio, were analysed in 99 elderly individuals (71.9 ± 5.8 years) diagnosed with hypertension (n = 51) or without hypertension (n = 48), using an eight-parameter flow cytometer. The percentage of CD4+ T lymphocytes was significantly higher in hypertensive than other individuals independently from CMV infections, with approximately 34% having CD4/CD8 > 2.5, and only 4% of the elderly with hypertension having CD4/CD8 < 1. The elderly with a normal BMI demonstrated the CD4/CD8 ratio ≥ 1 or ≤ 2.5, while overweight and obese participants showed a tendency to an inverted CD4/CD8 ratio. CD4/CD8 ratio increased gradually with age and reached the highest values in participants aged >75 years. The decline in CD4+ naïve T lymphocytes was more prominent in IgG CMV+ men when compared to IgG CMV+ women. The changes in naïve and memory T lymphocyte population, CD4/CD8, and CMV seropositivity included in IRP are important markers of health status in the elderly that are dependent on hypertension.

Obesity Increases Gene Expression of Markers Associated With Immunosenescence in Obese Middle-Aged Individuals

Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18). All groups (OBD, OB and E) performed the functional analyses [muscle strength (1RM) and cardiorespiratory fitness (VO2max)], anthropometry, body composition (Air Displacement Plethysmograph), blood collections for biochemical (anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16ink4a, CCR7, CD28 and CD27) analyses of markers related to immunosenescence. Increased gene expression of leptin, IL-2, IL-4, IL-10, TNF-α, PD-1, P16ink4a, CCR7 and CD27 was found for the OBD and OB groups compared to the E group. Moreover, VO2max for the OBD and OB groups was significantly lower compared to E. In conclusion, obesity, regardless of associated disease, induces increased gene expression of markers associated with inflammation and immunosenescence in circulating leukocytes in obese middle-aged individuals compared to a eutrophic group of the same age. Additionally, increased adipose tissue and markers of chronic inflammation and immunosenescence were associated to impairments in the cardiorespiratory capacity of obese middle-aged individuals.

Immunological aging and clinical consequences

Immunosenescence is defined as the changes in the immune system associated with age. It is a progressive and irreversible process involving a decrease in the number of naïve T and B cells, NK cells cytotoxic and activity, and disruption of pro and anti-inflammatory balance by altering the production of IL-2, -4, -6, -10, -10, TNF-α, interferon γ and others. With age there is an increase in autoimmunity and generalized inflammation with simultaneous immunodeficiency, which results in greater susceptibility to infectious diseases, a decrease in reactivity to prophylactic vaccinations, the incidence of autoimmune diseases, and increased risk of infectious injury complications, exacerbation of symptoms of chronic diseases and an insufficient response to the presence of cells cancer. For years, based on the analysis of the frequency of viral and bacterial infections, immunological indicators and inflammation, attempts have been made to develop the immune risk profile (IRP) and effective methods of preventing disorders of the immune system and prolonging the functional capacity of the elderly.

Collateral damage: Molecular aging and p16INK4a senescence protein in testicular cancer survivors treated with chemotherapy.

548 Background: Cytotoxic chemotherapy can cure patients with advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer patients exposed to chemotherapy. Methods: Case-control study of testicular cancer survivors (TCS) treated with chemotherapy (≥3 BEP cycles, disease-free ≥ 3 months) matched by age with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16INK4a expression was measured using real-time polymerase chain reaction, and the 2-ΔΔCt method was used for the p16INK4a expression analysis. Groups were compared with Mann-Whitney U test. Results are expressed as median (IQR) unless otherwise indicated. Results: We included 15 cases and 15 controls. Mean age 32.5 yo (24-54), mean time since last chemo 49.5 months (3-192). TCS had a lower percentage of CD3+ (62 (57-68) vs 72 (65-82) p = 0.026) and CD4+ (35 (27-41) vs 42 (38-53) p = 0.013) cells in total lymphocytes. TCS also had a lower % of naïve CD4+ (32 (15-44) vs 39 (32-55) p = 0.041), CD4+CD28+ (90 (85-97) vs 98 (95-99) p = 0.029) and CD8+ naïve (15 (8-26) vs 27 (22-42) p = 0.023) cells. TCS had an increased % of memory CD4+ (18 (13-26) vs 9 (6-11) p = 0.001) and memory CD19+ B cells (76 (62-88) vs 70 (64-79) p = 0.004). The relative expression of p16INK4a in CD3+ cells was higher in TCS compared to controls (1.29±0.36 vs 0.85±0.54; p = 0.035). Conclusions: TCS showed an increase in the expression of the aging biomarker p16INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory and CD28- cells. This phenomenon is believed to contribute to the development of an immune risk profile in the elderly, associated with an increased rate of infections and a diminished effect of vaccines. This is the first time this finding is reported in TCS. Further studies are warranted to define the clinical implications of this alteration.