title: Enhanced suicidal erythrocyte death contributing to anemia in the elderly.
abstract: OBJECTIVE
  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 Ca(2+)-concentration ([Ca(2+)]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, [Ca(2+)]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 [Ca(2+)]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.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Lupescu
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.forename: Tobias
authors.initials: T
authors.lastname: Goebel
authors.forename: Madhuri S
authors.initials: MS
authors.lastname: Salker
authors.forename: Kousi
authors.initials: K
authors.lastname: Alzoubi
authors.forename: Guilai
authors.initials: G
authors.lastname: Liu
authors.forename: Liviu
authors.initials: L
authors.lastname: Chirigiu
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging; D000740:Anemia / Q000097:blood* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D048429:Cell Size; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D017382:Reactive Oxygen Species