Fat metabolism is associated with telomere length in six population-based studies.

Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.

Genetic, parental and lifestyle factors influence telomere length.

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.

The effects of cryopreservation on red blood cell rheologic properties.

BACKGROUND: In transfusion medicine, frozen red blood cells (RBCs) are an alternative for liquid-stored RBCs. Little is known about the rheologic properties (i.e., aggregability and deformability) of thawed RBCs. In this study the rheologic properties of high-glycerol frozen RBCs and postthaw stored in saline-adenine-glucose-mannitol medium were compared to those of conventionally liquid-stored and fresh RBCs. STUDY DESIGN AND METHODS: Fresh RBCs were obtained from healthy volunteers. Leukoreduced liquid-stored and thawed deglycerolized RBC units were obtained from the Sanquin Blood Bank. RBCs were tested for aggregability (aggregation index [AI]), deformability (elongation index [EI]), and various hematologic variables. RESULTS: The AI of thawed RBCs was reduced, compared to fresh and liquid-stored RBCs (p<0.05). The EI of stored RBCs was significantly enhanced over a shear stress range of 2.0 to 50Pa compared to fresh RBCs (p<0.05). No significant differences in EI between thawed and 21- or 35-day liquid-stored RBCs were observed. The osmotic fragility, hemolysis, mean cell volume, and mean cell hemoglobin concentration of thawed RBCs were markedly altered, compared to fresh and liquid-stored RBCs (p< 0.05). The adenosine triphosphate (ATP) content of thawed RBCs was similar to 3- or 21-day liquid-stored and fresh RBCs. CONCLUSIONS: Thawed RBCs are more fragile than conventionally liquid-stored and fresh RBC. The freeze-thaw-wash process, however, did not adversely affect the aggregability and deformability or the ATP content of thawed RBCs. Based on the rheologic properties, cryopreserved RBCs are a valuable alternative to liquid-stored RBCs.

Is red blood cell rheology preserved during routine blood bank storage?

BACKGROUND: Red blood cell (RBC) units stored for more than 2 weeks at 4 degrees C are currently considered of impaired quality. This opinion has primarily been based on altered RBC rheologic properties (i.e., enhanced aggregability, reduced deformability, and elevated endothelial cell interaction), during prolonged storage of nonleukoreduced RBC units. In this study, the rheologic properties and cell variables of leukoreduced RBC units, during routine blood bank storage in saline-adenine-glucose-mannitol, were investigated. STUDY DESIGN AND METHODS: Ten leukoreduced RBC units were stored at the blood bank for 7 weeks at 4 degrees C. RBCs were tested weekly for aggregability, deformability, and other relevant variables. RESULTS: RBC aggregability was significantly reduced after the first week of storage but recovered during the following weeks. After 7 weeks aggregability was slightly, but significantly, reduced (46.9 + or - 2.4-44.3 + or - 2.2 aggregation index). During storage the osmotic fragility was not significantly enhanced (0.47 + or - 0.01% phosphate-buffered saline) and the deformability at shear stress of 3.9 Pa was not significantly reduced (0.36 + or - 0.01 elongation index [EI]). The deformability at 50 Pa was reduced (0.58 + or - 0.01-0.54 + or - 0.01 EI) but remained within reference values (0.53 + or - 0.04). During 5 weeks of storage, adenosine triphosphate was reduced by 54% whereas mean cell volume, pH, and mean cell hemoglobin concentration were minimally affected. CONCLUSIONS: RBC biochemical and physical alterations during storage minimally affected the RBC ability to aggregate and deform, even after prolonged storage. The rheologic properties of leukoreduced RBC units were well preserved during 7 weeks of routine blood bank storage.

Use of hydroxyethyl starch for inducing red blood cell aggregation.

UNLABELLED: Aggregation of human red blood cells (RBC) remains of biological and clinical interest. Replacement of plasma proteins by polymers to induce RBC aggregation may help to unravel the fundamentals of the aggregation process. Two theories exist to explain RBC aggregation mechanisms: a depletion and a bridging theory. RBC aggregation induced by hydroxyethyl starch (HES) increases with polymer size, which suggests that aggregation is induced via the bridging theory. In this study, the electrophoretic mobility (EPM) was measured to investigate RBC aggregation induced by 200 kDa HES polymers. Also, we evaluated if these polymers were useful for demonstrating aggregation differences between RBCs from healthy and type-1 diabetes mellitus (T1DM) subjects. Our results demonstrate that EPM values of RBCs in 200 kDa HES solutions were less negative than could be predicted by the viscosity of the suspension, supporting the bridging theory. Furthermore, aggregation analysis using the LORCA demonstrated that 200 kDa HES solution enhanced RBC aggregation of healthy and diabetic subjects similarly as standard 500 kDa dextran solutions. IN CONCLUSION: our data supports the bridging mechanism underlying 200 kDa HES induced RBC aggregation. In addition, both polymers are useful for demonstrating cellular induced aggregation differences between RBCs from healthy and T1DM subjects.