Aging and Cell Structure

Vo!ul1Je 1

Needlepoint of an electron microscopic view of a typical aging cell.

Commissioned especially for this treatise.

Woven by Jeanne Edwards of Seattle, Washington.

Aging and Cell Structure

Volume 1

Edited by

John E. Johnson, Jr. National Institute on Aging, NIH

Baltimore City Hospital and Johns Hopkins University School of Medicine

Baltimore, Maryland and

Hitachi Scientific Instruments Rockville, Maryland

PLENUM PRESS • NEW YORK AND LONDON

Library of Congress Cataloging in Publication Data

Main entry under title:

Aging and cell structure.

Bibliography: p. Includes index. 1. Cells-Aging. I. Johnson, John E., 1945-

Cells. WT 104 A2664] [DNLM: 1. Aging. 2.

L QH608.A37 574.87'6

ISBN-13: 978-1-4684-3931-1 DOl: 10.1007/978-1-4684-3929-8

© 1981 Plenum Press, New York

e-ISBN-13: 978-1-4684-3929-8

Softcover reprint of the hardcover 1 st edition 1981 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N. Y. 10013

All rights reserved

81-17886 AACR2

No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

"You will never escape from the lion in my heart." -ANONYMOUS, 1881

This volume is dedicated to those neophytes who would stir us from

the abyss of dogmatism.

Contributors

RALPH C. BALLARD Department of Biological Sciences, San Jose State University, San Jose, California 95192

STEVEN I. BASKIN Department of Pharmacology, The Medical College of Pennsyl­vania, Philadelphia, Pennsylvania 19129

KLAUS G. BENSCH Department of Pathology, Stanford University School of Medi­cine, Stanford, California 94305

WARREN KLINE BOL TON Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908

ANGELOS C. ECONOMOS Department of Biological Sciences, San Jose State Uni­versity, San Jose, California 95192. Present address: Laboratoire de Genetique, Universite Catholique de Louvain, Louvain-Ia-Neuve, Belgium

INGE GRUNDKE-IQBAL Department of Pathological Neurobiology, New York State Institute for Basic Research in Mental Retardation, Staten Island, New York 10314

KHALID IQBAL Department of Pathological Neurobiology, New York State Institute for Basic Research in Mental Retardation, Staten Island, New York 10314

JOHN E. JOHNSON, Jr. National Institute on Aging, Section on Experimental Mor­phology, Baltimore City Hospitals, Baltimore, Maryland 21224; Department of N eu­rology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and Hitachi Scientific Instruments, Rockville, Maryland 20850

ZEBULON V. KENDRICK Biokinetics Research Laboratory, College of HPERD, Tem­ple University, Philadelphia, Pennsylvania 19122

B. LEUNG Department of Neurology, Downstate Medical Center, Brooklyn, New York 11203

S. LEWIS Department of Neurology, Downstate Medical Center, Brooklyn, New York 11203

vii

viii CONTRIBUTORS

RONALD MERVIS Department of Pathology (Neuropathology), The Ohio State Uni­versity, College of Medicine, Columbus, Ohio 43210

JAIME MIQUEL Biomedical Research Division, NASA, Ames Research Center, Mof­fett Field, California 94035

JOSE OCHOA Department of Neurology, Dartmouth Medical School, Hanover, New Hampshire 03755

ALAN PETERS Department of Anatomy, Boston University School of Medicine, Bos­ton, Massachusetts 02118

JA Y ROBERTS Department of Pharmacology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129

H. S. SCHUTTA Department of Neurology, Downstate Medical Center, Brooklyn, New York 11203

S. A. SHAFIQ Department of Neurology, Downstate Medical Center, Brooklyn, New York 11203

RA YMOND S. SINA TRA Department of Pathological Neurobiology, New York State Institute for Basic Research in Mental Retardation, Staten Island, New York 10314

PETER S. SPENCER Institute of Neurotoxicology, Albert Einstein College of Medi­cine, Bronx, New York 10461

BENJAMIN C. STURGILL Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908

ROBERT J. TOMANEK Department of Anatomy, University of Iowa, Iowa City, Iowa 52240

EDGAR A. TONNA Institute for Dental Research, New York University Dental Cen­ter, New York, New York 10010

DEBORAH W. VAUGHAN Department of Anatomy, Boston University School of Medicine, Boston, Massachusetts 02118

HENRYK M. WISNIEWSKI Department of Pathological Neurobiology, New York State Institute for Basic Research in Mental Retardation, Staten Island, New York 10314

Foreword

Approaching any task on aging brings a flood of images that are a personal repetition of what has been one of the greatest and most persistent concerns of mankind. Even restricting time to the past decade or so and approaching only the biomedical sciences, one still encounters a flood of information in this relatively young research area. The­ories and ideas abound as though each researcher provides one of his own. This might well be expected; aging is an exceedingly complicated series of crossroads involving trails and even superhighways. Each specialist has a peephole (society, body, organ, tissue, cell, or-especially in modern biology-cellular organelles, macromolecules, and even molecules) and the views of the crossroads are obviously different. Hence, the num­ber of observations just about equals the number of independent ideas put forward.

It is natural to seek from highly specialized knowledge a fundamental understand­ing of aging through the modern research trends in biology that focus on events at the cellular, subcellular, macromolecular, and molecular levels. The ultimate clues must lie there-with one serious complication: There are numerous cell types in any body and each cell type is a very complex machine of its own. Additionally, there are potential repercussions in that different cells, tissues, and even molecules have effects on one another.

This is indeed a confusing situation, and one for which we must seek reliable answers, provided that we can take a step back and provide a generalized view. As we are dealing with multicellular organisms, the differences between body cells and germ cells hardly have to be emphasized, nor does the fact that body cells are particularly specialized and are so differentiated that they do not divide and are subject to wear and tear. Even within this group there is variation; for example, some tissues contain stem cells as well as differentiated ones and others contain only the latter.

The plan of this book, the first of a two-volume set, is to focus on a highly special­ized field-the structural features of aging cells-comparing different cell types and cell systems (including phylogenetic differences), and concentrating, where possible, on electron microscopy. This is essentially a book on biological ultrastructure that allows biological phenomena associated with aging to be looked at as structural patterns based on underlying physical and chemical events organized in space and time. J'he advances and the amount of information accumulated in the field of cellular fine structure in the

ix

x FOREWORD

past 30 years have been enormous, and integrated studies have come to the foreground. It is time for such studies on aging to be collected. This volume focuses on the nervous system, the principles and applications of the study of cell structure to aging, the kidney, skeletal aging, the cardiovascular system, skeletal muscle, and a comparison of insect vs. mammalian aging. What is revealed is a considerable and significant amount of data, as viewed through the ultrastructural peephole.

Russell J. Barrnett

Cell Biology Section Yale University School of Medicine New Haven, Connecticut

Preface

Do we love anything but the beautiful? What then is the beautiful, and what is beauty? What is it that attracts and wins us to the things we love? For unless there

were in them a grace and beauty, they could by no means draw us into them. The Confessions of St. Augustine, Book Four

The purpose of this first volume of Aging and Cell Structure is to bring together, in one publication, the latest data on what happens anatomically (focusing on electron micros­copy where possible) to living organisms as they grow older. The last book that dealt with this topic is almost a decade old and consisted primarily of light microscopy find­ings, and the data presented there were sparse in many areas. To be sure, several organ systems, even today, are only beginning to be studied from an anatomical point of view by gerontologists. The absence of certain subjects in this book is evidence of the lack of adequate research on many tissues. However, enough has been done in the 1970s, espe­cially on topics that have recently become important, to warrant a published volume. A second volume is being planned that will include systems and topics not covered in this volume.

My own interest in aging began in the field of the neurosciences when I discovered rather unusual inclusions in neuron processes of the lateral vestibular nucleus of aging rats. In discussing brain aging with numerous investigators, one point always was dif­ficult to resolve, namely, how does one know that changes observed in the aging brain are not a result of deterioration of other organs? For example, rodents, a popular model for gerontologists, are prone to liver tumors in old age. This includes the C57BL/6 mouse, so commonly used, as well as the rat lines. It is a question we may never be able to answer. However, it prompted me to compare the brains of old animals that had liver tumors with the brains of old animals without them. In the limited number of samples studied, no differences were observed. We then began studying the liver itself, finding swollen mitochondria in aged hepatocytes a most intriguing subject. We later discovered another interesting model for aging studies, almost totally unexplored in gerontology with the electron microscope: the testis. The reason it offers so much promise is that it contains, side by side, rapidly dividing cells (spermatogonia and spermatocytes) and postmitotic cells (Sertoli cells). These two basic cell types (dividing and postmitotic) playa major role in certain biological theories of the aging process.

In looking at these organ systems and others as well, we saw that there was a great void in the available literature on histological changes in these systems as they age. When I moved my laboratory to NIH, I decided that one of the first things I would do

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xii PREFACE

was to organize this book. I hope that the results of this effort will not only provide valuable information to the reader but also stimulate further research in this very important field.

John E. Johnson, Jr. Baltimore, 1981

Chapter 1. Central Nervous System Alan Peters and Deborah W Vaughan

1. Introduction .................................................... . 2. Dendritic Changes. . . . . .. . ......... . 3. Loss of Neurons ....................... . ........... . 4. Changes in Dendritic Spines . . . . . . . . . . . . . . . ........ . 5. Changes in Synaptic Populations. . . . . . . . . .. . ............... . 6. Changes in Cell Body and Nuclear Sizes ............................ . 7. Changes in Nucleoplasm . . . . . . . . . . . . . . . . ......... . 8. Changes in Neuronal Cytoplasm. . . . . . ........................ . 9. Neurofibrillary Tangles ........................ . ............ .

10. Lipofuscin .................................................... . 11. Neuroglia... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12. Choroid Plexus ............................................... .

References ..................................................... .

Chapter 2. The Mammalian Peripheral Nervous System in Old Age Peter S. Spencer and Jose Ochoa

1. Introduction................... . ............................ . 2. Age-Related Changes in Man. . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... .

2.1. General Comments ........................................... . 2.2. The Aging Sensory Unit. . . . . . . . . . . . . . . . . . . . . . .......... . 2.3. The Aging Motor Unit ........................................ . 2.4. The Aging Peripheral Autonomic System ........................ . 2.5. The Aging Peripheral Nerve of Man .............. .

3. Age-Related Changes in Animals . . . . . . . . . . . .................. . 3.1. General Comments. . . . . . . . . . . . . ............... . 3.2. The Aging Sensory Unit. . . . . . . . . . . . . . . . . . . . . . . . ...... . 3.3. The Aging Motor Unit. . . ............. . 3.4. The Aging Peripheral Autonomic System .......... . 3.5. The Aging Peripheral Nerve of Laboratory Animals

4. Concluding Remarks. . . .......................... . 4.1. Lipofuscin . . . . . . . . . . . ....... .

Contents

1 4

11 12 15 19 21 23 25 25 26 29 30

35 35 35 36 59 63 64 65 65 74 79 84 85 87 87

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xiv CONTENTS

4.2. Central-Peripheral Distal Axonopathy . 4.3. Proximal Demyelination. . . . . . . . . ...... . 4.4. Neuronal Loss ............................ . 4.5. Epilogue. References .

Chapter 3. Neurofibrillary and Synaptic Pathology in the Aged Brain Henryk M. Wisniewski, Raymond S. Sinatra, Khalid Iqbal, and Inge Grundke-Iqbal

1. Age-Associated Changes in the Human Brain ..................... . 2. Neurofibrillary Pathology. . ........ .

2.1. Normal Fibrillar Proteins in the CNS 2.2. Neurofibrillary Changes .................................. . 2.3. Experimentally Induced and Naturally Occurring Neurofibrillary

Changes. 3. Synaptic Pathology and Glial Reactions.

3.1. Morphology of the Neuritic Plaque. 3.2. Pathogenesis of the Neuritic Plaque . 3.3. Morphology of the Neuritic Changes 3.4. Role of Microglial Cells in Amyloid Deposition .. 3.5. Relationships between Amyloid Fibrils and PHFs . References ..

Chapter 4. Cytomorphological Alterations in the Aging Animal Brain with

Emphasis on Golgi Studies Ronald Mervis

1. Introduction. 1.1. The Use of Animal Models in Aging Research . 1.2. Memory Deficits in Aging Animals. 1.3. Neuronal Loss in Aging.

2. The Aging Brain: A Golgi Perspective 2.1. The Dendritic Tree and Its Spines 2.2. A Survey of Golgi-Impregnated Neuronal Changes in the Aging

Cerebral Cortex ..................... . 2.3. Age-Related Alterations in the Cerebellum-Purkinje Cells. 2.4. Golgi Studies of Dendritic Plasticity in the Adult and Aged Brain .

3. Electron Microscopy of the Aging Brain ............................. . 3.1. Lipofuscin ................................ . 3.2. Nuclear Membrane Infolding 3.3. Filamentous Accumulation. 3.4. Corpora Amylacea 3.5. Synaptic Alterations. 3.6. Tubulovesicular Profiles .............. . 3.7. Alterations in Myelinated Fibers ............ .

4. Discussion ...................................................... . 4.1. Golgi Studies .................... . 4.2. Electron Microscopy-Structural Changes in Aging Animal Brain

89 91 91 91 92

105 106 106 110

116 119 119 129 132 136 137 138

143 143 144 144 145 145

147 153 157 158 158 159 160 160 161 168 171 173 173 177

CONTENTS

5. Summary and Conclusions. References. . . . . . . . . . ...... .

Chapter 5. Variation: Principles and Applications in the Study of Cell Structure and Aging Angelos C. Economos. Jaime Miquel. Ralph C. Ballard. and John E. Johnson. Jr.

1. Origin of Variation. 2. Analysis of Variation ....... . 3. Variation and Aging. . ............................... . 4. Applications. . . . . . . . . . . ..... .

4.1. Variation in Mouse Liver Cellular and Fine Structure: Effects of Aging, Alcohol, and Antioxidants ......... .

4.2. Variation in Vitality and Mortality. . . ....... . 4.3. Time-Condensing in Experimental Aging Research through the Study

of Variation 5. Concluding Remarks. . ...... .

References.

Chapter 6. Ultrastructure of the Aging Kidney Warren Kline Bolton and Benjamin C. Sturgill

1. Introduction .. 2. Materials and Methods.

2.1. Rats 2.2. Humans . 2.3. Ultrastructural Studies.

3. Results. . ........... . 3.1. Rat Ultrastructural Studies .. 3.2. Clinicopathologic Correlations ..

4. Discussion References ........................ .

Chapter 7. Electron Microscopy of Skeletal Aging Edgar A. Tonna

1. Introduction. 2. Bone.

2.1. Periosteum. . . . . . . . . . . . . . . . . .. . ................ . 2.2. Endosteum. 2.3. Osteocytes 2.4. Osteoclasts. 2.5. Bone Surfaces .

3. Cartilage ...... . 3.1. General Cartilage Aging 3.2. Electron Microscopy of Aging Cartilage .......... .

4. Summary and Conclusions. References ......................... .

179 181

187 188 191 196

196 205

206 212 213

215 216 216 216 216 217 217 235 237 247

251 252 252 263 266 275 281 284 284 285 293 298

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xvi CONTENTS

Chapter 8. The Cardiovascular System

Steven I. Baskin, Zebulon V. Kendrick, Jay Roberts, and Robert J. Tomanek

1. Introduction .. 2. The Effect of Age on Physiological Parameters of the Cardiovascular System

2.1. Heart Rate and Electrocardiogram ..................... . 2.2. Blood Pressure. 2.3. Cardiac Output and Stroke Volume. 2.4. Contractile Properties. ..... . . . . . ......... . 2.5. Decline of Physical Work Capacity ...................... .

3. The Effect of Age on the Structure of the Myocardium .. 3.1. Connective Tissue. . ........... . 3.2. Myocardial Cell .................. .

4. The Effect of Age on Coronary Vessels. 5. The Effect of Age on the Reactivity of the Cardiovascular System to Drugs.

5.1. Age-Associated Changes in Pharmacokinetics of Drugs ......... . 5.2. Digitalis Glycosides .. 5.3. Autonomic Drugs 5.4. Antiarrhythmic Agents.

6. Summary. . ........... . References. . . . ............. .

Chapter 9. Fine Structure of Aging Skeletal Muscle S. A. Shajiq, S. Lewis, B. Leung, and H. S. Schutta

1. Introduction .. 2. Structural Changes in Human Muscle ............. . 3. Freeze-Fracture Studies ..

References.

Chapter 10. Insect vs. Mammalian Aging Jaime Miquel, Angelos C. Economos, and Klaus G. Bensch

1. Introduction ..... 2. Comparison of Tissue and Body Organization in Insects and Mammals .. 3. Fine Structural Manifestations of Aging

3.1. Age Pigment ............ . 3.2. Mitochondria .. 3.3. Ribosomes, Endoplasmic Reticulum Membranes, and RNA. 3.4. Nuclei ...... .

4. Comparison between Insect and Mammalian Aging .. 5. Conclusions ............ .

References ..

Index.

305 306 306 307 308 309 310 312 312 313 317 321 322 323 323 324 324 325

333 335 339 345

347 348 356 356 359 368 369 369 376 377

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Aging and Cell Structure

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