Erythrocyte Age Research Articles

Erythrocyte Aging, Protection via Vesiculation: An Analysis Methodology via Oscillatory Flow.

We demonstrate that erythrocyte deformations, specifically of a type as occur in splenic flow (Zhu et al., 2017), and of the type that promote vesiculation can be caused by simple, yet tailored, oscillatory shear flow. We show that such oscillatory shear flow provides an ideal environment to explore a wide variety of metabolic and biochemical effects that promote erythrocyte vesiculation. Deformation details, typical of splenic flow, such as in-folding and implications for membrane/skeleton interaction are demonstrated and quantitatively analyzed. We introduce a theoretical, essentially analytical, vesiculation model that directly couples to our more complex numerical, multilevel, model that clearly delineates various fundamental elements, i.e., sub-processes, that are involved and mediate the vesiculation process. This analytical model highlights particulary important vesiculation precursors such as areas of membrane/skeleton disruptions that trigger the vesiculation process. We demonstrate, using flow cytometry, that the deformations we experimentally induce on cells, and numerically simulate, do not induce lethal forms of cell damage but do induce vesiculation as theoretically forecasted. This, we demonstrate, provides a direct link to cell membrane/skeletal damage such as is associated with metabolic and aging damage. An additional noteworthy feature of this approach is the avoidance of artificial devices, e.g., micro-fluidic chambers, in which deformations and their time scales are often unrepresentative of physiological processes such as splenic flow.

Acoustophoretic Orientation of Red Blood Cells for Diagnosis of Red Cell Health and Pathology

Distortions of the normal bi-concave disc shape for red blood cells (RBCs) appear in a number of pathologies resulting from defects in cell membrane skeletal architecture, erythrocyte ageing, and mechanical damage. We present here the potential of acoustic cytometry for developing new approaches to light-scattering based evaluation of red blood cell disorders and of the effects of storage and ageing on changes or damage to RBCs membranes. These approaches could be used to immediately evaluate the quality of erythrocytes prior to blood donation and following transfusion. They could also be applied to studying RBC health in diseases and other pathologies, such as artificial heart valve hemolysis, thermal damage or osmotic fragility. Abnormal distributions of erythrocytes can typically be detected after just 30 to 45 seconds of acquisition time using 1–2 µL starting blood volumes.

Shortened mean erythrocyte age in female patients with type 2 diabetes mellitus.

The hyperglycemic state is known to shorten the erythrocyte life span. Erythrocyte creatine (EC) reflects the mean erythrocyte age and is useful as an indicator of hemolysis. Here, we studied the relationship between EC and glycemic control indicators [HbA1c or glycated albumin (GA)] in non-diabetic subjects and diabetic patients. This study included 119 patients with type 2 diabetes mellitus (T2DM) and 76 non-diabetic subjects matched by sex and age. We studied the relationships between EC and HbA1c or GA in patients with T2DM and non-diabetic subjects. Erythrocyte creatine in T2DM patients was significantly higher than that in non-diabetic subjects, and the ratio of high EC levels (>1.8μmol/g Hb) in T2DM patients was significantly higher as well. Furthermore, female EC was significantly higher than male EC, and the ratio of high EC levels in females was significantly higher than in the males as well. While male EC had no significant correlation with HbA1c or GA, female EC had significant positive correlations with both. Male EC had no significant difference between T2DM patients and non-diabetic subjects, while the EC in female patients with T2DM was significantly higher than in female non-diabetic subjects. The significant positive correlations of EC with HbA1c and GA in female patients with T2DM suggested that the mean erythrocyte age decreased in female diabetic patients with poor glycemic control.

Erythrocyte Senescence in a Model of Rat Displaying Hutchinson-Gilford Progeria Syndrome

Background Increased oxidative stress is a major cause of aging and age-related diseases. Erythrocytes serve as good model for aging studies. Dihydrotachysterol is known to induce premature aging feature in rats mimicking Hutchinson-Gilford progeria syndrome. Aim In the present study, attempts have been made to explore the differential response of young and senescent erythrocytes separated by density gradient centrifugation from accelerated senescence model of rats mimicking Hutchinson-Gilford progeria syndrome and naturally aged rats. Methods The erythrocytes of naturally aged and progeroid rats were separated into distinct, young and old cells on the basis of their differential densities. The parameters of oxidative stress and membrane transport systems were studied. Discussion and Conclusion Our study provides evidence that organismal aging negatively affects oxidative stress markers and membrane transport systems in both young and old erythrocytes. This study further substantiates that the changes in progeria model of rats resemble natural aging in terms of erythrocyte senescence.

Comparative Analysis of PKСα and PKCζ Activities in Rat and Lamprey Erythrocytes of Different Ages

The present study aimed to find out a link between ageing of rat and lamprey erythrocytes and activity of two isoforms of protein kinase C (PKC), РKСα and РKСζ. The whole cell population was separated into fractions of different ages in Percoll density gradient. The validity of separation was confirmed by the number of immature erythrocytes, reticulocytes. PKC activity was analyzed in cytosolic and membrane cell fractions. Rat erythrocytes express both PKC isoforms, РKСα and РKСζ, whereas lamprey erythrocytes express only РKСζ. РKСα is identified as a major band at ~ 80 kDa and minor bands at ~ 55–65 kDa; РKСζ is represented by a single band at ~ 80 kDa. In young rat erythrocytes, РKСα is detected mainly in cytosolic fractions, while in membrane fractions its level is by far lower. As cells age, PKCα is translocated from the cytosol to membranes and undergoes proteolytic degradation due to repeated cycles of activation. As a result, in aged erythrocytes relative total PKCα expression (as a sum of expressions in the cytosol and membranes per total protein level) diminishes, indicating a depletion of the PKCα pool and a decline in its functional activity. In both animal species, a highest PKCζ level is observed in the cytosol of young erythrocytes. Erythrocyte ageing is accompanied by a gradual decrease in expression of free cytosolic PKCζ and concurrent increase in the level of its membrane-bound forms. However, in contrast to PKCα, PKCζ is not proteolyzed; its total level in cells and perhaps functional activity do not change throughout the erythrocyte lifespan.

Labile haemoglobin as a glycaemic biomarker for patient-specific monitoring of diabetes: mathematical modelling approach.

Diabetes mellitus constitutes a major health problem and its clinical presentation and progression may vary considerably. A number of standardized diagnostic and monitoring tests are currently used for diabetes. They are based on measuring either plasma glucose, glycated haemoglobin or both. Their main goal is to assess the average blood glucose concentration. There are several sources of interference that can lead to discordances between measured plasma glucose and glycated haemoglobin levels. These include haemoglobinopathies, conditions associated with increased red blood cell turnover or the administration of some therapies, to name a few. Therefore, there is a need to provide new diagnostic tools for diabetes that employ clinically accessible biomarkers which, at the same time, can offer additional information allowing us to detect possible conflicting cases and to yield more reliable evaluations of the average blood glucose level concentration. We put forward a biomathematical model to describe the kinetics of two patient-specific glycaemic biomarkers to track the emergence and evolution of diabetes: glycated haemoglobin and its labile fraction. Our method incorporates erythrocyte age distribution and utilizes a large cohort of clinical data from blood tests to support its usefulness for diabetes monitoring.

Neocytolysis: How to Get Rid of the Extra Erythrocytes Formed by Stress Erythropoiesis Upon Descent From High Altitude.

Neocytolysis is the selective destruction of those erythrocytes that had been formed during stress-erythropoiesis in hypoxia in order to increase the oxygen transport capacity of blood. Neocytolysis likely aims at decreasing this excess amount of erythrocytes and hemoglobin (Hb) when it is not required anymore and to decrease blood viscosity. Neocytolysis seems to occur upon descent from high altitude. Similar processes seem to occur in microgravity, and are also discussed to mediate the replacement of erythrocytes containing fetal hemoglobin (HbF) with those having adult hemoglobin (HbA) after birth. This review will focus on hypoxia at high altitude. Hemoglobin concentration and total hemoglobin in blood increase by 20–50% depending on the altitude (i.e., the degree of hypoxia) and the duration of the sojourn. Upon return to normoxia hemoglobin concentration, hematocrit, and reticulocyte counts decrease faster than expected from inhibition of stress-erythropoiesis and normal erythrocyte destruction rates. In parallel, an increase in haptoglobin, bilirubin, and ferritin is observed, which serve as indirect markers of hemolysis and hemoglobin-breakdown. At the same time markers of progressing erythrocyte senescence appear even on reticulocytes. Unexpectedly, reticulocytes from hypoxic mice show decreased levels of the hypoxia-inducible factor HIF-1α and decreased activity of the BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), which results in elevated mitochondrial activity in these cells. Furthermore, hypoxia increases the expression of miR-21, which inhibits the expression of catalase and thus decreases one of the most important mechanisms protecting against oxygen free radicals in erythrocytes. This unleashes a series of events which likely explain neocytolysis, because upon re-oxygenation systemic and mitochondrial oxygen radical formation increases and causes the selective destruction of those erythrocytes having impaired anti-oxidant capacity.

Bacterial neuraminidase-mediated erythrocyte desialylation provokes cell surface aminophospholipid exposure.

Surface desialylation is associated with erythrocyte aging and mediates phagocytic recognition and clearance of senescent erythrocytes. Neuraminidases, a family of glycohydrolytic enzymes, cleave the glycosidic linkages between sialic acid and mucopolysaccharides and have previously been implicated in erythrocyte dysfunction associated with sepsis. Erythrocytes in septic patients further display a phenotype of accelerated eryptosis characterized by membrane phospholipid scrambling resulting in phosphatidylserine (PS) externalization. Herein, we examined the impact of artificial erythrocyte desialylation on eryptosis. Using flow cytometry and/or fluorescence microscopy, we analyzed desialylation patterns and eryptotic alterations in erythrocytes exposed to Clostridium perfringens-derived neuraminidase. Exogenous bacterial neuraminidase significantly augmented membrane PS exposure and cytosolic Ca2+ levels in a dose- and time-dependent manner. Neuraminidase treatment significantly reduced fluorescence-tagged agglutinin binding, an effect temporally preceding the increase in PS externalization. Neuraminidase-induced PS exposure was significantly curtailed by pretreatment with the pan-sialidase inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid. Neuraminidase treatment further induced hemolysis but did not significantly impact erythrocyte volume, ceramide abundance, or the generation of reactive oxygen species. Collectively, our data reveal that alteration of erythrocyte sialylation status by bacterial neuraminidase favors eryptotic cell death, an effect potentially contributing to reduced erythrocyte lifespan and anemia in sepsis.

Hematological indicators in pygmy wood mouse Apodemus uralensis (Muridae, Rodentia) populations as markers of the environmental radiation exposure: East Urals radioactive trace (Russia).

The hematological effects of chronic radiation exposure in males of the pygmy wood mouse (Apodemus uralensis Pall., 1811) from the East Urals radioactive trace (EURT) area were assessed, taking into account population abundance and reproductive status (immature, ripening, and mature yearlings). For this purpose, we analyzed the morpho-functional characteristics of erythrocytes (red cell indices [MCV, MCH, MCHC], red cell count, activity of antioxidant enzymes [GSH-Px, CAT], lipid peroxidation, glycolysis, osmotic resistance, methaemoglobin content) and blood plasma components (free hemoglobin, total lipids, total cholesterol, and glucose) in the background territory and the EURT area; these areas have a density of soil contamination with 90Sr of 12,851 and 198kBq × m-2, respectively (four and two order of magnitude higher than the background value). The data indicate the "hyperfunctional" state of the erythrocyte, aimed at activation of the gas transport function of blood in the radioactive environment. This, as a consequence, determines the insufficiency of energy supply of the cell defense system necessary to maintain the structural integrity of the membrane. Intensification of membrane lipid peroxidation, reduction of osmotic resistance and GSH-Px activity in red cells, an increase in the degree of intravascular hemolysis, and tendency towards erythropenia indicate the processes of accelerated aging of erythrocytes and their more pronounced destruction in the circulatory bed. The level of the hematological response increased with increasing radiation burden and was more pronounced with a large population size. The interaction effect of "overpopulation" and "radioactive pollution" was observed to a lesser degree for ripening males, and was very small for sexually mature animals. Immature males from the EURT head part with internal whole-body radiation doses of 0.0045-0.35mGy/day can be considered as the most sensitive group to the factors synergy, including radiation damage and overabundance population.

Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte aging

AbstractLutheran/basal cell adhesion molecule (Lu/BCAM) is a transmembrane adhesion molecule expressed by erythrocytes and endothelial cells that can interact with the extracellular matrix protein laminin-α5. In sickle cell disease, Lu/BCAM is thought to contribute to adhesion of sickle erythrocytes to the vascular wall, especially during vaso-occlusive crises. On healthy erythrocytes however, its function is unclear. Here we report that Lu/BCAM is activated during erythrocyte aging. We show that Lu/BCAM-mediated binding to laminin-α5 is restricted by interacting, in cis, with glycophorin-C–derived sialic acid residues. Following loss of sialic acid during erythrocyte aging, Lu/BCAM is released from glycophorin-C and allowed to interact with sialic acid residues on laminin-α5. Decreased glycophorin-C sialylation, as observed in individuals lacking exon 3 of glycophorin-C, the so-called Gerbich phenotype, was found to correlate with increased Lu/BCAM-dependent binding to laminin-α5. In addition, we identified the sialic acid–binding site within the third immunoglobulin-like domain within Lu/BCAM that accounts for the interaction with glycophorin-C and laminin-α5. Last, we present evidence that neuraminidase-expressing pathogens, such as Streptococcus pneumoniae, can similarly induce Lu/BCAM-mediated binding to laminin-α5, by cleaving terminal sialic acid residues from the erythrocyte membrane. These results shed new light on the mechanisms contributing to increased adhesiveness of erythrocytes at the end of their lifespan, possibly facilitating their clearance. Furthermore, this work may contribute to understanding the pathology induced by neuraminidase-positive bacteria, because they are especially harmful to patients suffering from sickle cell disease and are associated with the occurrence of vaso-occlusive crises.

Correlative study on the spectrum, characteristics and trend of unexplained fever in a hospital in Xinjiang

Objective A retrospective analysis was carried out for the classification and characteristics of fever of unknown origin, and its trend in recent years. Methods A total of 1 192 patients with fever of unknown origin, who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2010 to December 2016, were enrolled in this study. Descriptive analysis of the proportion, characteristics, and trend different diseases in the fever of unknown origin was performed. Results A total of 1 080 cases was diagnosed in 1 192 patients, with a diagnosis rate of 90.6%. The final diagnoses included infections, inflammatory diseases, malignancies and miscellaneous conditions in 72.9%, 9.1%, 5.1% and 3.4% of subjects, whereas 9.4% of cases remained undiagnosed. The results of variance analysis showed that the white blood cells and hemoglobin of infectious diseases were higher than those of connective tissue disease and malignancy were respectively [(11.12±2.58)×109/L vs (8.82±1.12)×109/L vs (9.67±2.76)×109/L, (116.81±20.77)g/L vs (103.25±22.84)g/L vs (102.30±25.14)g/L], While period of hospitalization and erythrocyte sedimentation rate were lower than that of connective tissue disease and malignancy were respectively [(12.15±7.91)days vs (19.94±10.17)days vs (18.85±14.37)days, (48.12±20.93)mm/h vs (58.13±20.24)mm/h vs (56.9±20.52)mm/h], and the age of malignant was higher than that of infectious disease and connective tissue disease were [(56.38±17.57)years vs (45.99±16.79)years vs (41.09±16.79)years], the difference was statistically significant (P<0.05). The rank sum test showed that eosinophils, lymphocytes and interleukin-6 were not equal (P<0.05). Conclusions Infectious diseases in fever of unknown origin (FUO) are still the main cause. whereas blood cells, eosinophils, lymphocytes, hemoglobin, erythrocyte sedimentation rate, interleukin 6, age and hospitalization time were predictive of disease diagnosis. In recent years, there was no obvious trend of all kinds of diseases. Key words: Fever/ET/EP; Hospitals/SN

ЭКОЛОГИЧЕСКАЯ И ЦИТОГЕНЕТИЧЕСКАЯ ХАРАКТЕРИСТИКА СТРУКТУРЫ ПОПУЛЯЦИИ СЕРЕБРЯНОГО КАРАСЯ (CARASSIUS AURATUSGIBELIO, BLOCH, 1782) ОЗЕРА СЕВАН (АРМЕНИЯ)

The article studies the morphological characteristics, age, sex structure, fecundity and cytomorphological parameters of erythrocytes of Crucian carp ( Carassius auratus gibelio , Bloch, 1782) from both subwatersheds (Big and Small) of Lake Sevan. The analysis of cyto-morphological characteristics of nuclei and erythrocytes showed that the population of the Crucian carp from the lake is heterogeneous as a whole, and consists of individuals with small (diploid) and large nuclei and erythrocytes (subgroups I and II). In sampling taken from both subwatersheds of Lake Sevan occurrence of individuals with the smallest nuclei (diploid individuals) made 38.8%. Crucian carps with the largest nuclei of red blood cells (subgroup II) are noted among females more than among males, with a low percentage of occurrences - 17.5%. The ratios of the volumes of the nuclei of erythrocytes and the number of nucleoli in the nuclei of erythrocytes of Crucian carps can be indicating the existence of triploid individuals in Lake Sevan. The number of Crucian carps with the largest nuclei of red blood cells (subgroup II, possibly triploids) is 17.5% in both subwatersheds of Lake Sevan. During the spawning period males prevailed to females in Small Sevan (1.5 ♂:1 ♀) and females prevailed to males in Big Sevan (1 ♂:1.6 ♀), which is the result of different spawning conditions in different parts of the lake. The highest role in the catch had individuals at the age of 3+. It has been established that the Crucian carp from Lake Sevan with large nuclei of erythrocytes do not differ statistically from individuals with small nuclei for all studied plastic and meristic characteristics and absolute individual fecundity.

Erythrocyte aging as a mechanism of anemia and a biomarker of device thrombosis in continuous-flow left ventricular assist devices

Blood trauma caused by continuous-flow left ventricular assist devices (CF-LVADs) has been associated with device thrombosis and anemia. Accurate in vivo quantification of erythrocyte turnover and its contribution to CF-LVAD complications have yet to be elucidated. We investigated the age (lifespan) of circulating erythrocytes in subjects with CF-LVAD. Erythrocyte lifespan is a quantitative indicator of in vivo erythrocyte turnover that can be accurately derived from measurement of the exhaled carbon monoxide (CO) level. Sixty non-smoking subjects were prospectively enrolled: 25 had a CF-LVAD without thrombosis; 10 had a CF-LVAD with thrombosis; and 25 were normal controls. End-tidal breath CO levels were measured and used to calculate erythrocyte lifespan. The mean erythrocyte lifespan was significantly shorter in CF-LVAD subjects with (29.7 ± 14.9 days) compared to those without (65.0 ± 17.3 days) device thrombosis (p < 0.0001). The lifespans in these 2 groups were significantly shorter compared with normal controls (96.0 ± 24.9 days, both p < 0.0001). A receiver operator curve demonstrated high sensitivity-specificity for use of erythrocyte lifespan to detect device thrombosis (AUC = 0.94). In addition, all CF-LVAD subjects had low hemoglobin (11.8 ± 2.0 g/dl), and their anemia was normochromic normocytic with elevated mean reticulocyte counts. Erythrocyte lifespan correlated significantly with mean corpuscular hemoglobin concentration (r = 0.56, p = 0.0005) and red cell distribution width (r = -0.65, p < 0.001), but not with reticulocyte count (r = 0.27, p = 0.32). Erythrocyte lifespan is substantially reduced in subjects with a CF-LVAD, which was more pronounced in the presence of device thrombosis. The etiology of anemia in CF-LVAD was primarily due to accelerated erythrocyte aging. Further studies are needed to determine whether erythrocyte lifespan could provide a practical means of detecting subtle pre-clinical thrombosis.

Modelling primaquine-induced haemolysis in G6PD deficiency.

Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose-dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable, this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0.75 mg/kg regimen for G6PDd. The model suggests that a step-wise increase in daily administered primaquine dose would be relatively safe in G6PDd. If this is confirmed, then were this regimen to be recommended for radical cure patients would not require testing for G6PDd in areas where G6PDd Viangchan or milder variants are prevalent.

Submicrometric Lipid Domains Play Key Roles in Erythrocyte Deformation: From Membrane Bending to Shape Restoration

Although direct evidence for lipid domains in living plasma membranes have been recently provided, their existence is still up for debate as their functions remain unclear. Vital imaging of the smooth erythrocyte plasma membrane allowed us to highlight two distinct populations of submicrometric domains with differential cholesterol and sphingomyelin enrichment. We here report direct evidence for the implication of these two domains in key steps of erythrocyte deformation, combining erythrocyte models exhibiting differential membrane curvature (healthy erythrocytes vs erythrocytes from patients with elliptocytosis and spherocytosis, two erythrocyte membrane fragility diseases), (de)stretching biophysical experiments and the decoration of endogenous cholesterol and sphingomyelin by specific fluorescent toxin fragments. Whereas cholesterol-enriched domains were implicated in the generation/maintenance of high membrane curvature areas needed for membrane bending, sphingomyelin-enriched domains were involved in calcium efflux during erythrocyte shape restoration. Our results indicate that cholesterol- and sphingomyelin-enriched domains play distinct key roles in erythrocyte deformation, as confirmed by the specific domain loss upon erythrocyte aging and erythrocyte deformability impairment upon domain abrogation by pharmacological approaches. Thus, whereas cholesterol- and sphingomyelin-enriched domains were so far highly associated, our findings give direct evidence for differential biophysical properties but also distinct physiopathological roles: (i) membrane bending modulators and/or stabilizers (cholesterol-enriched domains), (ii) platforms for protein sorting and/or activation (e.g. calcium efflux pump; sphingomyelin-enriched domains), and (iii) preferential fragility sites for membrane vesiculation (both domains).

Research progress of measurement methods of red blood cell survival and their applications

The measurement of red blood cell survival (RBCS)can help to understand the causes of various anemia and red blood cell breakdown, even more, it is the gold standard for the diagnosis of hemolytic anemia. However, so far, there is no appropriate method can be widely used in clinical for RBCS measurement. Here, we brief describ the mechanisms of red blood cells removing firstly, summarize the theory, detection steps, clinical applications, advantages and disadvantages of several measurement methods, such as 51Cr label, 15N-glycine label and biotin label, etc.. Then we focus on carbon monoxide (CO) breath test, a new method of RBCS measurement which had a broad scope in future clinical application. Key words: Erythrocyte aging; Chromium radioisotopes; Biotin; Carbon monoxide

Hemoglobin A1c and Race: Should Therapeutic Targets and Diagnostic Cutoffs Differ among Racial Groups?

Type 2 diabetes mellitus results from a combination of insulin resistance and inadequate insulin secretion, which together lead to impaired glucose homeostasis, culminating in hyperglycemia. Nonenzymatic attachment of glucose to a protein is termed glycation. The glucose concentration in blood modulates the extent of glycation of proteins in the circulation; higher glucose increases glycation. Hemoglobin A1c (Hb A1c)2 forms when glucose attaches to the N-terminal valine of the β chain of Hb A. Erythrocyte lifespan is approximately 120 days, and Hb A1c thus reflects the mean blood glucose concentration over the preceding 8–12 weeks. As a marker of chronic glycemia, Hb A1c is used extensively in individuals with diabetes to predict complications and monitor therapy, with target values established for optimal treatment (1). More recently, the use of Hb A1c was advocated for screening and diagnosis of diabetes (1). Several different methods, including immunoassay, HPLC, affinity chromatography, capillary electrophoresis, and enzymatic assay, are used to measure Hb A1c. Importantly, assay standardization has resulted in equivalent values among methods (2). Like other analytes, Hb A1c is not perfect. The main limitation is that the Hb A1c concentration may be altered by factors other than glycemia (3). In particular, any condition that changes erythrocyte lifespan will change Hb A1c. Examples include severe thalassemia, hereditary spherocytosis, splenomegaly, autoimmune hemolytic anemia, and some hemoglobin variants. Conceptually, this problem could be eliminated if one could apply a factor to correct for erythrocyte age. However, it is extremely difficult to measure erythrocyte lifespan, thus precluding the use of this strategy. Chronic renal failure is a common complication of diabetes. Patients with chronic renal failure have lower Hb A1c due to shortened erythrocyte survival. In many of these patients, erythropoietin is used …

Glycated Hemoglobin, Plasma Glucose, and Erythrocyte Aging.

The relationship between HbA1c and blood glucose averages has been characterized many times, yet, a unifying, mechanistic description is still lacking. We calculated the level of HbA1c from plasma glucose averages based solely on the in vivo rate of hemoglobin glycation, and the different turnover rates for erythrocytes of different ages. These calculations were then compared to the measured change of HbA1c due to changes in mean blood glucose (MBG), to complex models in the literature, and our own experiments. Analysis of data on erythrocyte ageing patterns revealed that 2 separate RBC turnover mechanisms seem to be present. We calculated the mean red blood cell (RBC) life span within individuals to lie between 60 and 95 days. Comparison of expected HbA1c levels to data taken from continuous glucose monitors and finger-stick MBG yielded good agreement (r = .87, P < .0001). Experiments on the change with time of HbA1c induced by a change of MBG were in excellent agreement with our calculations (r = .98, P < .0001). RBC turnover seems to be dominated by a constant rate of cell loss, and a mechanism that targets cells of a specific age. Average RBC life span is 80 ± 10.9 days. Of HbA1c change toward treatment goal value, 50% is reached in about 30 days. Many factors contribute to the ratio of glycated hemoglobin, yet we can make accurate estimations considering only the in vivo glycation constant, MBG, and the age distribution of erythrocytes.

Erythrocyte senescence and membrane transporters in young and old rats

Alterations at the level of plasma membrane are reported to play an important role in cellular senescence. The present study was undertaken to correlate cellular senescence, membrane transport processes and organismal aging. To achieve this objective activities of membrane linked Na+/K + ATPase (NKA), Na+/H+ exchanger (NHE) and correlation with membrane hydrxyperoxide level, sialic acid content and membrane protein oxidation was studied in density-gradient fractionated young and old erythrocytes from 4 and 24 month old Wistar rats. The results reveal that cellular aging within the tissue is associated with significant decrease in activities of NKA and NHE of senescent erythrocytes in comparison to younger cell population of same age group. The result shows that impaired ion homeostasis due to altered membrane transporters including functional and compositional changes may be one of the reasons responsible behind rat erythrocyte aging.

Evaluation of Intravascular Hemolysis With Erythrocyte Creatine in Patients With Aortic Stenosis

Chronic intravascular hemolysis has been identified in patients with cardiac valve prostheses, but only a few case reports have evaluated intravascular hemolysis in patients with native valvular heart disease. To detect intravascular hemolysis in patients with aortic stenosis, erythrocyte creatine was evaluated with hemodynamic indices obtained by echocardiography.Erythrocyte creatine, a marker of erythrocyte age, was assayed in 30 patients with aortic stenosis and 10 aged matched healthy volunteers. Peak flow velocity of the aortic valve was determined by continuous-wave Doppler echocardiography. Twenty of 30 patients with aortic stenosis had high erythrocyte creatine levels (> 1.8 µmol/g Hb) and erythrocyte creatine was significantly higher as compared with control subjects (1.98 ± 0.49 versus 1.52 ± 0.19 µmol/g Hb, P = 0.007). Peak transvalvular pressure gradient ranged from 46 to 142 mmHg and peak flow velocity ranged from 3.40 to 5.95 m/second. Patients with aortic stenosis had a significantly lower erythrocyte count (387 ± 40 versus 436 ± 42 × 10(4) µL, P = 0.002) and hemoglobin (119 ± 11 versus 135 ± 11 g/L, P < 0.001) as compared with control subjects. Erythrocyte creatine had a fair correlation with peak flow velocity (r = 0.55, P = 0.002).In conclusion, intravascular hemolysis due to destruction of erythrocytes was detected in patients with moderate to severe aortic stenosis and the severity of intravascular hemolysis was related to valvular flow velocity of the aortic valve.