Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study.
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SUBMITTER: den Elzen WP
PROVIDER: S-EPMC3659927 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Backgroundreduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is important to know both the extent and limitations of this association. We investigated the relation between telomere length and anaemia in two independent cohorts, with the prior expectation of adding anaemia to the list of conditions for which telomere reduction is a risk factor.Participants and methodsthe present study is embedded in the Newcastle 85-plus Study and Leiden 85-plus Study, two population-based studies of inhabitants of Newcastle and North Tyneside, UK (n = 749) and Leiden, the Netherlands (n = 658) aged 85 and over. High-molecular-weight DNA was isolated from full fresh blood (Newcastle) and peripheral blood mononuclear cells samples (Leiden). Telomere length was measured as abundance of telomeric template versus a single gene by quantitative real-time polymerase chain reaction. Anaemia was defined according to World Health Organization criteria.Resultsin both studies, no differences in median telomere length were observed between participants with anaemia and participants without anaemia (Newcastle: 2,846 bp (interquartile range (IQR) 2,433-3,630) versus 2,920 bp (IQR 2,425-3,570), P = 0.63; Leiden: 4,136 bp (IQR 3,879-4,428) versus 4,167 bp (IQR 3,893-4,501), P = 0.41). Telomere length also did not correlate with any other haematological parameter in both men and women.Conclusionsin contrast to other age-related diseases, telomere length is not associated with anaemia or any other haematological parameter in older individuals in the general population.
| S-EPMC3114621 | biostudies-literature
Project description:ObjectiveTo study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old.MethodsIn 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years.ResultsSubjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 0.187). Subjects in the category "highest tertile of NT-proBNP and the lowest tertile of systolic BP" had a 3.7-point-lower MMSE score at baseline (p < 0.001) and a 0.49-point-steeper decline in MMSE score per year (p < 0.001) compared with subjects in the other categories.ConclusionsIn the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction.
| S-EPMC4176025 | biostudies-literature
Project description:In the aging society, it is important to identify very old persons at high risk of functional decline, cardiovascular disease and mortality. However, traditional risk markers lose their predictive value with age. We investigated whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels predict change in functional status, cardiovascular morbidity and mortality in very old age. Here we present an observational prospective cohort study (Leiden 85-plus Study, 1997-2004) in a population-based sample of 560 individuals aged 85 years with a 5-year complete follow-up for functional status, cardiovascular morbidity and cause-specific mortality. Median NT-proBNP for men was 351 pg/ml (cutoff values for low-medium tertiles 201 pg/ml and medium-high tertiles 649 pg/ml) and, for women, 297 pg/ml (cutoffs 204 and 519 pg/ml, respectively). During the 5-year follow-up, participants with high NT-proBNP had an accelerated cognitive decline and increase of activities of daily living (ADL) disability over time (all at p?<?0.01) and an increased risk of incident heart failure [hazard ratio (HR) 3.3 (95 % confidence interval (CI) 1.8-6.1)], atrial fibrillation [HR 4.1 (2.0-8.7)], myocardial infarction [HR 2.1 (1.2-3.7)], stroke [HR 3.4 (1.9-6.3)], cardiovascular mortality [HR 5.5 (3.1-10)], non-cardiovascular mortality [HR 2.0 (1.4-3.0)] and all-cause mortality [HR 2.9 (2.1-4.0)], independent of other known risk markers. All results remained similar after exclusion of participants with heart failure at baseline. In very old age, high-NT-proBNP levels predict accelerated cognitive and functional decline, as well as cardiovascular morbidity and mortality. Results suggest that NT-proBNP can help clinicians to identify very old people at high risk of functional impairment and incident cardiovascular morbidity.
| S-EPMC4082596 | biostudies-literature
Project description:BackgroundVisual impairment frequently occurs amongst older people. Therefore, the aim of this study was to investigate the predictive value of visual impairment on functioning, quality of life and mortality in people aged 85 years.MethodsFrom the Leiden 85-plus Study, 548 people aged 85 years were eligible for this study. Visual acuity was measured at baseline by Early Treatment Diabetic Retinopathy Study charts (ETDRS). According to the visual acuity (VA) three groups were made, defined as no (VA > 0.7), moderate (0.5 ≤ VA ≤ 0.7) or severe visual impairment (VA < 0.5). Quality of life, physical, cognitive, psychological and social functioning were measured annually for 5 years. For mortality, participants were followed until the age of 95.ResultsAt baseline, participants with visual impairment scored lower on physical, cognitive, psychological and social functioning and quality of life (p < 0.001). Compared to participants with no visual impairment, participants with moderate and severe visual impairment had an accelerated deterioration in basic activities of daily living (respectively 0.27-point (p = 0.017) and 0.35 point (p = 0.018)). In addition, compared to participants with no visual impairment, the mortality risk was 1.83 (95% CI 1.43, 2.35) for participants with severe visual impairment.DiscussionIn very older adults, visual impairment predicts accelerated deterioration in physical functioning. In addition, severely visually impaired adults had an increased mortality risk. A pro-active attitude, focussing on preventing and treating visual impairment could possibly contribute to the improvement of physical independence, wellbeing and successful aging in very old age.
| S-EPMC9074345 | biostudies-literature
Project description:Backgroundprevention of disability is an important aim of healthcare for older persons. Selection of persons at risk is a first crucial step in this process.Objectivesthis study investigates the predictive value of multimorbidity for the development of disability in the general population of very old people and the role of cognitive impairment in this association.Designthe Leiden 85-plus Study (1997-2004) is an observational prospective cohort study with 5 years of follow-up.Settinggeneral population of the city of Leiden, the Netherlands.Subjectspopulation based sample of 594 participants aged 85 years.Methodsdisability in activities of daily living (ADL) was measured annually for 5 years with the Groningen Activity Restriction Scale (range 9-36, 9 = optimal). Multimorbidity is defined as the presence of two or more chronic diseases at age 85 years. Cognitive function was measured at baseline with the mini-mental state examination (MMSE).Resultsat baseline participants with multimorbidity had higher ADL disability scores compared with those without [median 11 inter-quartile range (IQR 9-16) versus 9 (IQR 9-13) ADL points, Mann-Whitney U test P < 0.001]. Stratified into four MMSE groups, ADL disability increased over time in all groups, even in participants without multimorbidity (P trend <0.001). Multimorbidity predicted accelerated increase in ADL disability in participants with MMSE of 28-30 points (n = 205, 0.67 points/year, P < 0.001), but not in participants with lower MMSE scores (all P > 0.100).Conclusionthe predictive value of multimorbidity for the increase in ADL disability varies with cognitive function in very old people. In very old people with good cognitive function, multimorbidity predicts accelerated increase in ADL disability. This relation is absent in very old people with cognitive impairment.
| S-EPMC3080242 | biostudies-literature
Project description:The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level.
| S-EPMC3667775 | biostudies-literature
Project description:BackgroundThe epsilon2, epsilon3, and epsilon4 alleles of the apolipoprotein E gene (APOE) encode three isoforms, apoE2, E3, and E4, respectively. The apoE isoforms circulate in different plasma concentrations, but plasma concentrations of the same isoform also differ between individuals. Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown.Methods and findingsWe assessed APOE genotypes, plasma levels of apoE, cardiovascular risk factors, and mortality in a population-based sample of 546 individuals aged 85 y who participated in the Leiden 85-plus Study and were prospectively followed for specific causes of death for 5 y. Participants in the highest tertile of apoE levels suffered a twofold-increased risk of cardiovascular mortality (hazard ratio compared to lowest tertile, 2.08; 95% confidence interval [CI], 1.30 to 3.33). Among the 324 participants with the epsilon3epsilon3 genotype, the hazard from cardiovascular disease was threefold increased (highest versus lowest tertile 3.01; 95% CI 1.60 to 5.66), with similar estimates for men and women. Other causes of death were not increased significantly. Plasma levels of apoE in epsilon3epsilon3 participants were positively correlated with total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and triglycerides (p < 0.001) and negatively with high-density lipoprotein cholesterol levels (p = 0.010). Adjustment for plasma lipids did not change the hazard ratios, whereas interaction was absent. The risk associated with high levels of apoE, however, was strongest in participants from the lowest tertile of C-reactive protein (CRP) levels and absent in those from the highest tertile (p(interaction) < 0.001). Among participants from the lowest tertile of CRP levels, those with a high apoE levels had a significantly steeper increase in CRP than those with low apoE levels (p = 0.020). Similar cardiovascular mortality risks as in epsilon3epsilon3 participants were found in epsilon2 and epsilon4 carriers.ConclusionsIn old age, high plasma apoE levels precede an increase of circulating CRP and strongly associates with cardiovascular mortality, independent of APOE genotype and plasma lipids.
| S-EPMC1457005 | biostudies-literature
Project description:AimsFew studies have investigated primary age-related tauopathy (PART) in a population-based setting. Here, we assessed its prevalence, genetic background, comorbidities and features of cognitive decline in an unselected elderly population.MethodsThe population-based Vantaa 85+ study includes all 601 inhabitants of Vantaa aged ≥ 85 years in 1991. Neuropathological assessment was possible in 301. Dementia (DSM IIIR criteria) and Mini-Mental State Examination (MMSE) scores were assessed at the baseline of the study and follow-ups. PART subjects were identified according to the criteria by Crary et al and were compared with subjects with mild and severe Alzheimer's disease (AD) neuropathological changes. The effects of other neuropathologies were taken into account using multivariate and sensitivity assays. Genetic analyses included APOE genotypes and 29 polymorphisms of the MAPT 3' untranslated region (3'UTR region).ResultsThe frequency of PART was 20% (n = 61/301, definite PART 5%). When PART subjects were compared with those with severe AD pathology, dementia was less common, its age at onset was higher and duration shorter. No such differences were seen when compared with those with milder AD pathology. However, both AD groups showed a steeper decline in MMSE scores in follow-ups compared with PART. APOE ε4 frequency was lower, and APOE ε2 frequency higher in the PART group compared with each AD group. The detected nominally significant associations between PART and two MAPT 3'UTR polymorphisms and haplotypes did not survive Bonferroni correction.ConclusionsPART is common among very elderly. PART subjects differ from individuals with AD-type changes in the pattern of cognitive decline, associated genetic and neuropathological features.
| S-EPMC9305229 | biostudies-literature
Project description:This work extrapolates to humans the previous animal studies on blood heterochronicity and establishes a novel direct measurement of biological age. Our results support the hypothesis that, similar to mice, human aging is driven by age-imposed systemic molecular excess, the attenuation of which reverses biological age, defined in our work as a deregulation (noise) of 10 novel protein biomarkers. The results on biological age are strongly supported by the data, which demonstrates that rounds of therapeutic plasma exchange (TPE) promote a global shift to a younger systemic proteome, including youthfully restored pro-regenerative, anticancer, and apoptotic regulators and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Mechanistically, the circulatory regulators of the JAK-STAT, MAPK, TGF-beta, NF-κB, and Toll-like receptor signaling pathways become more youthfully balanced through normalization of TLR4, which we define as a nodal point of this molecular rejuvenation. The significance of our findings is confirmed through big-data gene expression studies.
| S-EPMC9398900 | biostudies-literature
Project description:Hepcidin, the master regulator of systemic iron homeostasis, tightly influences erythrocyte production. High hepcidin levels block intestinal iron absorption and macrophage iron recycling, causing iron restricted erythropoiesis and anemia. Low hepcidin levels favor bone marrow iron supply for hemoglobin synthesis and red blood cells production. Expanded erythropoiesis, as after hemorrhage or erythropoietin treatment, blocks hepcidin through an acute reduction of transferrin saturation and the release of the erythroblast hormone and hepcidin inhibitor erythroferrone. Quantitatively reduced erythropoiesis, limiting iron consumption, increases transferrin saturation and stimulates hepcidin transcription. Deregulation of hepcidin synthesis is associated with anemia in three conditions: iron refractory iron deficiency anemia (IRIDA), the common anemia of acute and chronic inflammatory disorders, and the extremely rare hepcidin-producing adenomas that may develop in the liver of children with an inborn error of glucose metabolism. Inappropriately high levels of hepcidin cause iron-restricted or even iron-deficient erythropoiesis in all these conditions. Patients with IRIDA or anemia of inflammation do not respond to oral iron supplementation and show a delayed or partial response to intravenous iron. In hepcidin-producing adenomas, anemia is reverted by surgery. Other hepcidin-related anemias are the "iron loading anemias" characterized by ineffective erythropoiesis and hepcidin suppression. This group of anemias includes thalassemia syndromes, congenital dyserythropoietic anemias, congenital sideroblastic anemias, and some forms of hemolytic anemias as pyruvate kinase deficiency. The paradigm is non-transfusion-dependent thalassemia where the release of erythroferrone from the expanded pool of immature erythroid cells results in hepcidin suppression and secondary iron overload that in turn worsens ineffective erythropoiesis and anemia. In thalassemia murine models, approaches that induce iron restriction ameliorate both anemia and the iron phenotype. Manipulations of hepcidin might benefit all the above-described anemias. Compounds that antagonize hepcidin or its effect may be useful in inflammation and IRIDA, while hepcidin agonists may improve ineffective erythropoiesis. Correcting ineffective erythropoiesis in animal models ameliorates not only anemia but also iron homeostasis by reducing hepcidin inhibition. Some targeted approaches are now in clinical trials: hopefully they will result in novel treatments for a variety of anemias.
| S-EPMC6794341 | biostudies-literature