The Role of Inflammation in Age-Associated Changes in Red Blood System.

Aging-related anemia contributes to frailty syndrome, cognitive decline and early mortality. The study aim was to evaluate inflammaging in relation to anemia as a prognostic indicator in affected older patients. The participants (73.0 ± 7.2 years) were allocated into anemic (n = 47) and non-anemic (n = 66) groups. The hematological variables RBC, MCV, MCH, RDW, iron and ferritin were significantly lower, whereas erythropoietin EPO and transferrin Tf tended toward higher values in the anemic group. Approx. 26% of individuals demonstrated transferrin saturation TfS < 20%, which clearly indicates age-related iron deficiency. The cut-off values for pro-inflammatory cytokine IL-1ß, TNFα and hepcidin were 5.3 ng/mL, 97.7 ng/mL and 9.4 ng/mL, respectively. High IL-1ß negatively affected Hb concentration (rs = -0.581, p < 0.0001). Relatively high odds ratios were observed for IL-1ß (OR = 72.374, 95%Cl 19.688-354.366) and peripheral blood mononuclear cells CD34 (OR = 3.264, 95%Cl 1.263-8.747) and CD38 (OR = 4.398, 95%Cl 1.701-11.906), which together indicates a higher probability of developing anemia. The results endorse the interplay between inflammatory status and iron metabolism and demonstrated a high usefulness of IL-1ß in identification of the underlying causes of anemia, while CD34 and CD38 appeared useful in compensatory response assessment and, in the longer term, as part of a comprehensive approach to anemia monitoring in older adults.

Immunosenescence in Aging-Related Vascular Dysfunction.

The immunosenescence-related disproportion in T lymphocytes may have important consequences for endothelial dysfunction, which is a key event in vascular aging. The study was designed to assess the prognostic values of the inflammatory-immune profile to better predict and prevent vascular diseases associated with old age. Eighty individuals aged 70.9 ± 5.3 years were allocated to a low- (LGI) or high-grade inflammation (HGI) group based on CRP (<3 or ≥3 mg/L) as a conventional risk marker of cardiovascular diseases. Significant changes in inflammatory and endothelium-specific variables IL-1ß, IL-6, TNFα, oxLDL, H2O2, NO, 3-nitrotyrosine, and endothelial progenitor cells (OR 7.61, 95% CI 2.56−29.05, p < 0.0001), confirmed their interplay in vascular inflammation. The flow-cytometry analysis demonstrated a high disproportion in T lymphocytes CD4+ and CD8+ between LGI and HGI groups. CRP was <3 mg/mL for the CD4/CD8 ratio within the reference values ≥ 1 or ≤2.5, unlike for the CD4/CD8 ratio < 1 and >2.5. The odds ratios for the distribution of CD4+ (OR 5.98, 95% CI 0.001−0.008, p < 0.001), CD8+ (OR 0.23, 95% CI 0.08−0.59, p < 0.01), and CD8CD45RO+ T naïve cells (OR 0.27, 95% CI 0.097−0.695, p < 0.01) and CD4/CD8 (OR 5.69, 95% CI 2.07−17.32, p < 0.001) indicated a potential diagnostic value of T lymphocytes for clinical prognosis in aging-related vascular dysfunction.

Anemia and Its Connections to Inflammation in Older Adults: A Review.

Anemia is a common hematological disorder that affects 12% of the community-dwelling population, 40% of hospitalized patients, and 47% of nursing home residents. Our understanding of the impact of inflammation on iron metabolism and erythropoiesis is still lacking. In older adults, anemia can be divided into nutritional deficiency anemia, bleeding anemia, and unexplained anemia. The last type of anemia might be caused by reduced erythropoietin (EPO) activity, progressive EPO resistance of bone marrow erythroid progenitors, and the chronic subclinical pro-inflammatory state. Overall, one-third of older patients with anemia demonstrate a nutritional deficiency, one-third have a chronic subclinical pro-inflammatory state and chronic kidney disease, and one-third suffer from anemia of unknown etiology. Understanding anemia's pathophysiology in people aged 65 and over is crucial because it contributes to frailty, falls, cognitive decline, decreased functional ability, and higher mortality risk. Inflammation produces adverse effects on the cells of the hematological system. These effects include iron deficiency (hypoferremia), reduced EPO production, and the elevated phagocytosis of erythrocytes by hepatic and splenic macrophages. Additionally, inflammation causes enhanced eryptosis due to oxidative stress in the circulation. Identifying mechanisms behind age-related inflammation is essential for a better understanding and preventing anemia in older adults.

The Association of Anti-Inflammatory Diet Ingredients and Lifestyle Exercise with Inflammaging.

One of the latest theories on ageing focuses on immune response, and considers the activation of subclinical and chronic inflammation. The study was designed to explain whether anti-inflammatory diet and lifestyle exercise affect an inflammatory profile in the Polish elderly population. Sixty individuals (80.2 ± 7.9 years) were allocated to a low-grade inflammation (LGI n = 33) or high-grade inflammation (HGI n = 27) group, based on C-reactive protein concentration (<3 or ≥3 mg/L) as a conventional marker of systemic inflammation. Diet analysis focused on vitamins D, C, E, A, ß-carotene, n-3 and n-6 PUFA using single 24-h dietary recall. LGI demonstrated a lower n-6/n-3 PUFA but higher vitamin D intake than HGI. Physical performance based on 6-min walk test (6MWT) classified the elderly as physically inactive, whereby LGI demonstrated a significantly higher gait speed (1.09 ± 0.26 m/s) than HGI (0.72 ± 0.28 m/s). Circulating interleukins IL-1ß, IL-6, IL-13, TNFα and cfDNA demonstrated high concentrations in the elderly with low 6MWT, confirming an impairment of physical performance by persistent systemic inflammation. These findings reveal that increased intake of anti-inflammatory diet ingredients and physical activity sustained throughout life attenuate progression of inflammaging in the elderly and indicate potential therapeutic strategies to counteract pathophysiological effects of ageing.

Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease.

Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe PAD. The study included 59 patients (females n = 17, males n = 42) aged 67.0 ± 8.2 years classified into two groups based on ankle-brachial index (ABI) measurements (ABI ≤ 0.9 n = 43, ABI ≤ 0.5 n = 16). A total of 60 subjects aged 70.4 ± 5.5 years (females n = 42, males n = 18) with ABI > 0.9 constituted a reference group. NPT concentration reached values above 10 nmol/L in patients with PAD, which differed significantly from reference group (8.15 ± 1.33 nmol/L). High levels of CRP > 5 mg/L, TC > 200 mg/dL as well as lipoproteins LDL > 100 mg/dL and non-HDL > 130 mg/dL were found in the same group, indicating the relationship between NPT and conventional atherogenic markers. The endothelial progenitor cells (EPCs) tended toward lower values in patients with ABI ≤ 0.5 when compared to reference group, and inversely correlated with NPT. These findings indicate a crucial role of NPT in atheromatous process and its usefulness in monitoring PAD severity. However, the role of NPT in chronic PAD needs further studies including relatively high number of subjects.

Intermittent Hypoxic Exposure Reduces Endothelial Dysfunction.

Intermittent exposure to hypoxia (IHE) increases the production of reactive oxygen and nitrogen species as well as erythropoietin (EPO), which stimulates the adaptation to intense physical activity. However, several studies suggest a protective effect of moderate hypoxia in cardiovascular disease (CVD) events. The effects of intense physical activity with IHE on oxi-inflammatory mediators and their interaction with conventional CVD risk factors were investigated. Blood samples were collected from elite athletes (control n = 6, IHE n = 6) during a 6-day IHE cycle using hypoxicator GO2 altitude. IHE was held once a day, at least 2 hours after training. In serum, hydrogen peroxide (H2O2), nitric oxide (NO), 3-nitrotyrosine (3-Nitro), proinflammatory cytokines (IL-1ß and TNFα), high sensitivity C-reactive protein (hsCRP), and heat shock protein 27 (HSP27) were determined by the commercial immunoenzyme (ELISA kits) or colorimetric methods. Serum erythropoietin (EPO) level was measured by ELISA kit every day of hypoxia. IHE was found to significantly increase H2O2, NO, and HSP27 but to decrease 3NT concentrations. The changes in 3NT and HSP27 following hypoxia proved to enhance NO bioavailability and endothelial function. In the present study, the oxi-inflammatory mediators IL-1ß and hsCRP increased in IHE group but they did not exceed the reference values. The serum EPO level increased on the 3rd day of IHE, then decreased on 5th day of IHE, and correlated with NO/H2O2 ratio (r s = 0.640, P < 0.05). There were no changes in haematological markers contrary to lipoproteins such as low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) which showed a decreasing trend in response to hypoxic exposure. The study demonstrated that IHE combined with sports activity reduced a risk of endothelial dysfunction and atherogenesis in athletes even though the oxi-inflammatory processes were enhanced. Therefore, 6-day IHE seems to be a potential therapeutic and nonpharmacological method to reduce CVD risk, especially in elite athletes participating in strenuous training.