Background/Aims: Anemia, a common condition in the elderly, could result from impaired formation and/or from accelerated loss of circulating erythrocytes. The latter could result from premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca2+-concentration ([Ca2+]i), oxidative stress and ceramide. The present study explored whether eryptosis is altered in elderly individuals and, if so, to identify underlying mechanisms. Methods: Blood was drawn from healthy young (n=11, age 31.3±1.7 years) and elderly (n=16, age 88.6±0.9 years) individuals. PS exposure was estimated from annexin V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from 2',7'dichlorodihydrofluorescein fluorescence, reduced glutathione (GSH) from mercury orange fluorescence and ceramide from FITC-conjugated antibody binding in flow cytometry. Measurements were made in erythrocytes from freshly drawn blood and in erythrocytes exposed in vitro for 24 h to plasma from young or elderly individuals. Results: Elderly individuals suffered from severe anemia (hemoglobin 10.5±0.3 g/100 ml) despite enhanced number of reticulocytes (2.3±0.2%). The percentage of PS-exposing erythrocytes was significantly higher in the elderly (2.5±0.2%) than in the young volunteers (1.3±0.1%). The increase in PS exposure was paralleled by significant increase of ROS and significantly decreased levels of reduced GSH. Erythrocyte [Ca2+]i, and ceramide abundance tended to be higher in the elderly, differences, however, not reaching statistical significance. Conclusions: The anemia of elderly individuals is mainly if not exclusively due to enhanced eryptosis, resulting at least in part from GSH deficiency and increased oxidative stress.
Recently, a congenital myasthenic syndrome (CMS) with end‐plate acetylcholine receptor (AChR) deficiency due to missense mutations in the genes for the AChR subunit was described. The first observed patient with this CMS was heteroallelic for the two ε‐AChR subunit mutations ε1101insT and ε1293insG. This patient had only a moderate phenotype with mild muscle weakness and abnormal fatigue. We have now found homozygosity for the ε1293insG mutation in a severely affected CMS patient, who lost the ability to walk in midchildhood and shows profound weakness and muscle wasting. Our observation allows a genotype‐phenotype correlation illustrating how differences in the AChR mutation haplotype can profoundly influence disease severity. Ann Neurol 2000;48:379–383
Recently, a congenital myasthenic syndrome (CMS) with end-plate acetylcholine receptor (AChR) deficiency due to missense mutations in the genes for the AChR subunit was described. The first observed patient with this CMS was heteroallelic for the two epsilon-AChR subunit mutations epsilon1101insT and epsilon1293insG. This patient had only a moderate phenotype with mild muscle weakness and abnormal fatigue. We have now found homozygosity for the epsilon1293insG mutation in a severely affected CMS patient, who lost the ability to walk in midchildhood and shows profound weakness and muscle wasting. Our observation allows a genotype-phenotype correlation illustrating how differences in the AChR mutation haplotype can profoundly influence disease severity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.