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228 Pages·1988·5.244 MB·English
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Blood Cells, Rheology, and Aging Edited by Dieter Platt With 67 Figures and 47 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Professor Dr. med. DIETER PLATT Direktor des Instituts fUr Gerontologie der Universitat Erlangen-Niirnberg und der 2. Medizinischen Klinik Klinikum Niirnberg, FlurstraBe 17 D-8500 Niirnberg, FRG ISBN-13: 978-3-642-71792-5 e-ISBN-13: 978-3-642-71790-1 DOl: 10.1007/978-3-642-71790-1 Library of Congress Cataloging-in-Publication Data. Blood cells, rheology and aging. Based on the third Erlangen-Nuremberg symposium held in 1986. Includes index. 1. Erythrocytes ~ Aging ~ Congresses. 2. Lymphocytes ~ Aging ~ Congresses. 3. Blood ~ Viscosity ~ Age factors ~ Congresses. I. Platt, Dieter. [DNLM: 1. Aging ~ congresses. 2. Blood Cells ~ congresses. 3. Blood Circulation ~ congresses. 4. Erythrocyte Aging ~ congresses. WH 150 B6542 1986) QP96.B54 1988 599:0113 87-28881 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication ofthis publication or parts thereof is only permitted under the previsions of the German Copyright Law of September 9,1965, in its version of June 24,1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1988 Softcover reprint of the hardcover 1st edition 1988 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. 2122/3130-543210 List of Contributors E. BEREGI, Prof. Dr., Gerontology Center Med. University, 1085 Somogyi Bela U 33, Budapest, Hungary D. E. BROOKS, Prof. Dr., University of British Columbia, Department of Pathology, 2075 Westbrook Place, Vancouver, British Columbia, Canada V6T1 W5 G. CASALE, Prof. Dr., Istituto de Gerontologia e Geriatria, Universita degli Studi di Pavia, Piazza Borromeo n. 2, 27100 Pavia, Italy M.-P. CHANG, Prof. Dr., Geriatric Center, VA Wadsworth Hospital Center, 691-11 GA VA Wadsworth Hospital, Wilshire and Sawtelle BLVDS, Los Angeles, CA 90073, USA D. DANON, Prof. Dr., Bella S. & Irving E. Meller, Center for Biology of Aging, The Weizmann Institute, Rehovot, Israel D. DRENCKHAHN, Prof. Dr., Institut fUr Anatomie und Zellbiologie der UniversWit Marburg, 3550 Marburg, FRG D. GERSHON, Prof. Dr., Technion Institute, Technion City, Haifa, 32000, Israel H. GERSHON, Prof. Dr., Technion Faculty of Medicine, Dept. Immunology, 12 Aliah St., Haifa, 32000, Israel G. A. GLASS, Prof. Dr., Technion Institute, Technion City, Haifa, 32000, Israel K. HAGER, Dr., 2. Med. Klinik, Klinikum Niirnberg, 8500 Niirnberg, FRG L. HAYFLICK, Prof. Dr., Center for Gerontological Studies, University of Florida, Gainesville, USA H. HECKERS, Prof. Dr., Zentrum fUr Innere Medizin der Universitat GieBen, 6300 GieBen, FRG I. HERMANN, Prof. Dr., 2. Med. Klinik, Klinikum Niirnberg, 8500 Niirnberg, FRG F. JUNG, Dr., Abt. fUr Klinische Haemostaseologie und Transfusionsmedizin, Universitatskliniken des Saarlandes, 6650 Homburg/Saar, FRG VI List of Contributors N. KHANSARI, Prof. Dr., Department of Microbiology, North Dakota State University, Fargo, North Dakota, 58105, USA H. KIESEWETIER, Prof. Dr. Dr., Abt. fUr Klinische Haemostaseologie und Transfusionsmedizin, Universitiitskliniken des Saarlandes, 6650 Homburg/Saar, FRG N. KINOHARA, Prof. Dr., Geriatric Center, VA Wadsworth Hospital Center, 691-11 GA VA Wadsworth Hospital, Wilshire and Sawtelle BLVDS, Los Angeles, CA 90073, USA A. KNYSZYNSKI, Prof. Dr., Bella S. & Irving E. Meller, Center for Biology of Aging, The Weizmann Institute, Rehovot, Israel N. KORBER, Dr., Abteilung Neurologie der Medizinischen Fakultiit der RWTH Aachen, Pauwelsstrasse, 5100 Aachen, FRG O. LINDERKAMP, Prof. Dr., University of Heidelberg, 6900 Heidelberg, FRG T. MAKINODAN, Prof. Dr., Director Geriatric Center, VA Wadsworth Hospital Center, 691-11 GA VA Wadsworth Hospital, Wilshire and Sawtelle BLV DS, Los Angeles, CA 90073, USA H. J. MEISELMAN, Prof. Dr.,. Department of Physiology, USC School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033, USA G. B. NASH, Dr., St. George's Hospital Medical School, London, UK P. DE NICOLA, Prof. Dr., Istituto de Gerontologia e Geriatria, Universita degli Studi di Pavia, Piazza Borromeo n.2, 27100 Pavia, Italy H. P. NUTTGENS, Dr., Abt. fUr Klinische Haemostaseologie und Transfusionsmedizin, Universitiitskliniken des Saarlandes, 6650 Homburg/Saar, FRG J. PALEK, Prof. Dr., Haematology Research Laboratory, St. Elizabeths Hospital, 736 Cambridge Street, Boston, Massachusetts, 02135, USA C. PFAFFEROTH, Dr., 1. Medizinische Klinik rechts der Isar, Technische Universitiit Miinchen, Ismaninger Str. 22, 8000 Miinchen 80, FRG D. PLATT, Prof. Dr., Institut fUr Gerontologie der Universitiit Erlangen-Niimberg und 2. Med. Klinik, Klinikum Niimberg, 8500 Niimberg, FRG W. RIECK, Dr., Institut fUr Gerontologie der Universitiit Erlangen Niimberg, 8500 Niimberg, FRG E. B. RINGELSTEIN, Prof. Dr., Abteilung Neurologie der Medizinischen Fakultiit der RWTH Aachen, Pauwelsstrasse, 5100 Aachen, FRG List of Contributors VII G. S. ROTH, Prof. Dr., Gerontological Research Center, National Institute of Aging, Baltimore, MD 21224, USA R. SCHNEIDER, Dr., Abteilung fUr Neurologie der Medizinischen Fakultat der RWTH Aachen, Pauwelsstrasse, 5100 Aachen, FRG T. VOMEL, Priv.-Doz. Dr., Institut fUr Gerontologie der Universitat Erlangen-Niirnberg, 8500 Niirnberg, FRG TH. B. WAHLBERG, Prof. Dr., Department of Blood Coagulation Disorders, Karolinska Hospital, Stockholm, Sweden R. L. WALFORD, Prof. Dr., Department of Pathology, UCLA Medical School, Los Angeles, CA 90024, USA M. E. WEKSLER, Prof. Dr., Cornell University, Medical College, 1300 York Avenue, New York, N.Y. 10021, USA S. WOLF, Dr., Abteilung Ophthalmologie der Rheinisch-Westfalischen Technischen Universitat, 5100 Aachen, FRG Preface In the third Erlangen-Nuremberg symposium on experimental geronto logy we discussed the effect of aging on blood cells and rheology. Most studies with red cells have been performed on humans, rats, and rabbits. All these erythrocytes have no nucleus; the cells are therefore a model in which new synthesis of proteins is impossible. All the processes are age dependent except for exchange with the plasma. Investigations of red cells have attracted attention because of the latter's availability in large quantities from biochemists, physiologists, immunologists, and micro scopists. We now have a relative abundance of data on the biochemical and immunologic composition as well as on the ultrastructure of the cells. The second topic under discussion at the symposium was the immune system and cell receptors. One of the most apparent features of aging of the organism is progressive dysregulation of the immune system. As a result, the incidence of infection, cancer, and autoimmune and immune complex diseases increases. While we have a lot of new data on the function and differentiation of lymphoid cells, we have little informa tion on lymphocyte receptors during the aging process. Rheologic studies reflect changes in red cell deformability and blood coagulation. The erythrocyte deformability influences blood flow in all parts of the circulation. The fluidity of the red cell membranes controls whole blood viscosity. During aging, there are significant alterations in blood coagulation and hemostasis. One of the best known modifications of blood co agulation is a typical thrombophilic tendency with aging. For this symposium, we brought together 25 scientists from eight countries. As gerontology is an interdisciplinary subject, workers of different disciplines were invited. I hope that the papers and discussions from this meeting will expand our knowledge of red cells, immunology, receptors, blood coagulation, and rheology. I except that this book will provide a firm foundation for future work in the area. Finally, I wish to thank the pharmaceutical industry, especially Dr. Bauer and Mr. Hansen, for the financial assistance provided for the meeting. Erlangen-Niimberg DIETER PLATT Contents Hemopoiesis as a Model for the "Biological Clock". D. DANON, A. KNYSZYNSKI, and L. HAYFLICK With 6 Figures . . . . . . . . . . . . . . . . . 1 Red Cell Membrane Skeleton: Assembly and Function. J. PALEK. . . . . . . . . . . . . . . . . . . . . . . . . 13 Red Cell Membrane Lipids and Aging. H. HECKERS and D. PLATT With 4 Figures and 6 Tables . . . . . . . . 16 Red Cell Membrane Proteins, Glycoproteins, and Aging. D. PLATT and W. RIECK With 9 Figures and 1 Table . . . . . . . . . . . . . . . . 29 The Effect of Host and Cell Age on the Rat Erythrocyte: Biochemical Aspects. D. GERSHON, G. A. GLASS, and H. GERSHON With 5 Tables . . . . . . . . . . . . . . . . . . . 42 The Effect of Host and Cell Age on the Rat and Human Erythrocyte: Cellular and Immunologic Aspects. H. GERSHON, G. A. GLASS, and D. GERSHON With 3 Figures and 5 Tables . . . . . . . . . . . . . . . . 51 Removal of Old and Abnormal Red Blood Cells from Circulation: Mechanical and Immunologic Mechanisms. D. DRENCKHAHN With 8 Figures and 1 Table . . . . . . . . . . . . . 62 Mechanism for Elimination of Senescent Red Blood Cells from Circulation. N. KHANSARI With 1 Figure and 6 Tables . . . . . . . . . . .. ... 77 The Influence of Pi race tam on the Age-Dependent Rate of Phagocytosis (in the Isolated Perfused Rat Liver). T. VOMEL and D. PLATT With 4 Figures and 3 Tables . . . . . . . . . . . . . . . . 90 XII Contents Changes in Human Red Cell Mechanics During In Vivo Aging: Possible Influence on Removal of Senescent Cells. G. B. NASH, O. LINDERKAMP, C. PFAFFEROTH, and H. J. MmsELMAN With 4 Figures and 3 Tables . . . . . . . . . . . . . . . . 99 Age-Related Physiologic and Molecular Changes in the Thymus. T. MAKINODAN, N. KINOHARA, and M.-P. CHANG With 5 Figures and 1 Table . . . . . . . . . . . . . . . . 113 The Cellular Basis and Clinical Significance of Immune Senescence. M. E. WEKSLER . . . . . . . . . . . . . . . . . . .. 122 Regulation of the Immune and Nonimmune Aging Process by the Major Histocompatibility Complex. R. L. WALFORD With 3 Tables . . . . . . . . . . . . . . . . . .. 127 Age-Related Morphologic Changes in Lymphocytes. E. BEREGI With 9 Figures . . . . . . . . . . . . . . . . . 139 Receptor and Postreceptor Changes During Lymphocyte Aging. G. S. ROTH ........................ 150 Mechanism of Red Cell Aggregation. D. E. BROOKS .......... . . 158 Fluidity of Blood of Elderly Patients and Rheologic Therapies. H. KIESEWETTER, F. JUNG, N. KORBER, H. P. NUTTGENS, S. WOLF, R. SCHNEIDER, and E. B. RINGELSTEIN With 9 Tables . . . . . . . . . . . . . . . . . . . .. 163 Hemostasis, Microcirculation, and Thrombophilia in the Aged. P. DE NICOLA and G. CASALE With 7 Figures . . . . . . . . . . . . . . . . . . . .. 177 Influence of Age, Sex, and Blood Group on Blood Coagulation. TH. B. WAHLBERG With 3 Figures . . . . . . . . . . . . . . . . . . .. 194 Fibrinogen in the Aged - Functional and Structural Aspects. K. HAGER, I. HERMANN, and D. PLATT With 4 Figures and 4 Tables 201 SUbject Index. . . . . . . 215 Hemopoiesis as a Model for the "Biological Clock" D. DANON, A. KNYSZYNSKI, and L. HAYFLICK Introduction Cultured normal human cells have a finite capacity for replication in vitro [1]. It has been shown that embryo-derived fibroblasts which have the greatest capacity ± for replication in vitro, undergo 50 10 population doublings before division ceases in about 10-12 months. The events are divided into three phases. Phase I represents the primary culture, phase II the active replication period, and phase III the period when cell replication slows, ceases, and ultimately ends with com plete cell degeneration and death. It was suggested that the phase III phenomenon might represent aging at the cellular level [1, 2]. Research conducted in the ensu ing years has confirmed the finitude of normal cell replication in vitro and has substantially supported the suggestion that the phenomenon represents aging at the cellular level (for reviews see refs. 3-8). The finitude of normal cell replication in vitro implies the existence of a "biological clock." The erythroid nucleus is expelled during the process of differentiation of the mammalian erythrocyte [9, 10]. There are four discrete divisions in the develop ment of mature erythrocytes. The stem cells divide into proerythroblasts in which a small amount of hemoglobin can be detected in the cell cytoplasm. The proery throblasts differentiate into basophilic erythrocytes in which the chromatin is somewhat coarse and nucleoli are no longer discernible. As hemoglobin produc tion increases the cells become polychromatic erythrocytes with densely staining chromatin bodies in the nucleus. In the final stage of differentiation, the cells, cal led normoblasts, have almost the same amount of hemoglobin as the mature erythrocytes and the chromatin is denser and more compact than in the polychro matophilic cells. Eventually the nuclei become pyknotic, and are extruded from the cells along with a narrow rim of cytoplasm and apparently intact outer cell membrane. The cytoplasmic components and the reticulocytes mature into eryth rocytes and the expelled nuclei are soon phagocytized by macrophages. The process of nuclear expulsion has been studied in several laboratories, in cluding our own [11]. This process represents an ultimate differentiation of a cell in which the genetic material is eliminated after four divisions. There is, in this phenomenon, a definite and a very precise limit to the number of population dou blings of the erythroid cells in vivo. Similar to phase III in the tissue cultured nor mal fibroblasts, the expulsion of the erythroid nucleus ends the cell divisions. This phenomenon may therefore be analogous to the in vivo expression of a "biolog ical clock." An important question now arises: Is the nucleus expelled because it died and is eliminated from the cell as a deteriorated organelle, or is the mecha- Blood Cells, Rheology, and Aging Ed. by D. Platt © Springer-Verlag Berlin Heidelberg 1988

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