Table Of ContentNEUROBIOLOGY
OF AGING
An Interdisciplinary Life-Span Approach
ADVANCES IN BEHAVIORAL BIOLOGY
Editorial Board:
Jan Bures Institute of Physiology, Prague, Czechoslovakia
Irwin Kopin National Institute of Mental Health, Bethesda, Maryland
Bruce McEwen Rockefeller University, New York, New York
James McGaugh University of California, Irvine, California
Karl Pribram Stanford University School of Medicine, Stanford, California
Jay Rosenblatt Rutgers University, Newark, New Jersey
Lawrence Weiskrantz University of Oxford, Oxford, England
Recent Volumes in this Series
Volume 8 • DRUGS AND THE DEVELOPING BRAIN
Edited by Antonia Vernadakis and Norman Weiner' 1974
Volume 9 • PERSPECTIVES IN PRIMATE BIOLOGY
Edited by A. B. Chiarelli· 1974
Volume 10· NEUROHUMORAL CODING OF BRAIN FUNCTION
Edited by R. D. Myers and Rene Ra~1 Drucker-Colfn • 1974
Volume 11. REPRODUCTIVE BEHAVIOR
Edited by William Montagna and William A. Sadler. 1974
Volume 12. THE NEUROPSYCHOLOGY OF AGGRESSION
Edited by Richard E. Whalen' 1974
Volume 13· ANEURAL ORGANISMS IN NEUROBIOLOGY
Edited by Edward M. Eisenstein' 1975
Volume 14, NUTRITION AND MENTAL FUNCTIONS
Edited by George Serban • 1975
Volume 15' SENSORY PHYSIOLOGY AND BEHAVIOR
Edited by Rachel Galun, Peter Hillman, Itzhak Parnas,
and Robert Werman' 1975
Volume 16 • NEUROBIOLOGY OF AGING
Edited by J. M. Ordy and K. R. Brizzee' 1975
A Continuation Order Plan is available for this series. A continuation order will bring
delivery of each new volume immediately upon pUblication. Volumes are billed only upon
actual shipment. For further information please contact the publisher.
NEUROBIOLOGY
OF AGING
An Interdisciplinary Life-Span Approach
Edited by
J. M. Ordy
Head, Department of Neurobiology
Delta Regional Primate Research Center
Tulane University
Covington, Louisiana
and
K. R. Brizzee
Head, Division of Biomedical Sciences
Delta Regional Primate Research Center
Covington, Louisiana
and
Department of Anatomy
Tulane University School of Medicine
New Orleans, Louisiana
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Neurobiology of aging.
(Advances in behavioral biology; v. 16)
Includes bibliographies and index.
1. Aging. 2. Neurobiology. I. Ordy, J. M.II. Brizzee, K. R. [DNLM: 1. Aging.
2. Neurophysiology. W3 AD215 v. 6 / WT104 N495]
QP86.N48 612'.8 75-19441
ISBN-13: 978-14684-0927-7 e-ISBN-13: 978-1-4684-O92~
001: 10.10071978-14684-0925-3
© 1975 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1975
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, NW10 6SE, England
All rights reserved
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
Preface
Aging is one of the most universal and inevitable social and sci
entific challenges confronting man. The lives of all multicellular
organisms begin with conception, extend through phases of development,
maturity, senescence and finally end in death. Man is no exception,
but has the unique feature of a complex brain. It plays an integra
tive role in adaptation to the physical and social environments
through reflexes, conditioning and more complex forms of learning. The
brain is a repository for both inherited and acquired information.
With the development of speech and the formation of symbolic language,
the human brain has made it possible to transmit information cultur
ally (horizontal) to other members of society, in addition to genetic
(vertical) transmission to progeny. This horizontal transmission,
which has reached its highest form in man, is a powerful extension of
genetic transmission. The brain may provide man all that is of im
portance in life. It has played a key role in the evolution of life
by maintaining and extending the life span.
Many mental or intellectual capacities of man reach a peak in
early adulthood, remain relatively constant throughout maturity and
then appear to decline during senescence. Behaviorally, there appears
to be a decrease in sensory, learning and motor functions with aging
in all mammalian species. As integrated adaptive control systems,
the brain and neuroendocrines have been closely associated with the
homeostatic adaptation to environmental challenges throughout .the
life span.
Interdisciplinary neurobiological studies have indicated that
sensory, learning, motor processes and biological drives can be re
lated to the structural and functional organization of the nervous
and neuroendocrine systems. Recent research trends include: 1) In
terdisciplinary attempts to bridge the gaps from behavioral to
electrical, neurochemical, morphological and molecular levels of or
ganization, 2) More emphasis on not only the interrelationships among
neurons, but also among glia, the neuropil, extracellular "space" or
microenvironment and vascular elements, including the blood-brain
barrier, 3) The environmental modifiability (physiological, chemical
and morphological "plasticity" of the brain and neuroendocrines) not
v
vi PREFACE
only during development but also during maturity and aging, and 4)
An increasing emphasis on life~pan studies that consider develop
ment, maturity and aging as integrated aspects of an ontogenetic pro
gram. rather than as separate and distinct stages of the life span.
As an interdisciplinary science, gerontology includes: sociology,
psychology, bioch~mistry, morphology and biomedical sciences. As a
hybrid discipline, neurobiology has undergone a remarkable expansion
in recent years. However, this rapid progress has occurred primari
ly in research on brain development rather than on aging. Very re
cently, there has been an increasing social and scientific interest
in aging. This concern is based in part on the increasing propor
tion of the population over 65 in leading industrial nations. Many
of the human problems of aging also include an increa.sing incidenr::e
of mental impairmepts and brain disorders. Clarification of the
aging process in the brain requires an interdisciplinary approach
covering the entire life span. The chapters in this book were se
lected to present and integrate the currently available knowledge on
age-related functional and structural changes in the human brain.
It seems that the new field of "neurobiology and aging" will
attract increasing numbers of investigators from many disciplines.
It is hoped that this book will be of interest to a broad audience,
ranging from undergraduate to graduate students, biological as well
as social scientists, medical students, practicing physicians and
other interested members of society. It seems likely that the fu
ture direction and progress in neurobiology and aging will vindicate
the interdisciplinary life span approach.
ACKNOWLEDGEMENTS
The editors wish to acknowledge the overall support provided by
the Delta Regional Primate Research Center of Tulane University
and NIH Grant No. RR 00164. Thanks are due Dr. P. J. Gerone, the
Center Directur, for his endorsement of this project.
We are most grateful to Bernice Kaack for the versatUle contri
butions in all phases of the preparation of this volume.
We are indebted to Wilma Martin who prepared many of the high
quality illustrations used in this volume. We are also grateful to
Mercedes Fussell, Joan Hinton, Mary LaCroix and Earl Rodriguez for
their patience, perserverance and understanding in the typing of all
manuscripts.
J. MaJr..k. 0n dy
Kenneth R. Bnizzee
Contents
I. Definitions, theories, methods, molecular, cellular, organ
and species difference in aging
1. Principles of mammalian aging 1
J. M. O!'d;j
2. Role of the nervous system in aging; correlations among
life span, brain-body weight and metabolism •••••••.•••• 23
W. J. Hansche
3. Relation of development and aging; pre- and postnatal
differentiation of the brain as related to aging ••••••• 37
O. J. Schjeide
II. Psychophysiological changes in aging
4. The nervous system, behavior and aging; an interdiscip
linary life-span approach . • • • • • • • • . • • • • • • • . • . • • • • • • • • .• 85
J. M. O!'dy
5. Sensory processes in man during maturity and senes-
cence •••••••••.••.•••••••.•.•••••••••••••..••••..••••.• 119
J. F. Co!'so
6. Changes in learning and memory during aging •.•••••.•••• 145
P. E. Gold and J. L. McGaugh
7. Two efferent systems; potential for later-life
changes ••••••••••••.•••••.•••••••••••••••..•.••..••••.• 159
J. D. Mase!'
III.Neurophysiological changes in the nervous system in aging
8. Life span changes in the electrical activity of the hu
man brain as reflected in the cerebral evoked re-
sponse •••••••••••••.••..•••••..•.••.••.•••.•.••..•..•.• 175
E. C. Beck, R. E. Dustman and T. Schenkenbe!'g
vii
viii CONTENTS
9. Changes in neuromuscular relationships in aging ••••••• 193
E. Gutmann and V. HanzZikova
10. Changes in limbic, neuroendocrine and autonomic sys-
tems, adaptation. homeostasis during aging •••••••••••• 209
B. Kaaak, J. M. Drdy and B. Trapp
11. Autoimmunity and aging of the nervous system •••••.•••• 233
R. W. Lang and D. J. CarZo
IV. Neurochemical changes in the nervous system in aging
12. Neurochemical changes in composition, metabolism
and neurotransmitters in the human brain with
age •••••••••••••••••••••.••.•••••••••••••••.••••••••• '253
J. M. Drdy and B. Kaaak
13. Age changes in the human for some enzymes associated
with metabolism of catecholamines. GABA and ace-
tylcholine ••••••••••••••••••••••••••••••••••••••••••• '287
E. G. MaGeer and P. L. MaGeer
14. Age-related changes in nucleic acids and protein
synthesis •••••••••••••••••••••••••.•••••••••••••••••• '307
R. L. Herrmann
15. Neurochemistry of the developing and aging mammalian
brain ••••••••••••••••••••••••••••••• ~ •••••••••••••••• '329
J. Davis and W. A. Himwiah
16. Changes in brain lipids in aging •••••.••••••.••••••.••3 59
L. A. Horroaks, G. Y. Sun and R. A. D'Amato
17. Age pigment: a biochemical indicator of intracellu-
lar aging •••••••••••••••••••••••••••••••••••••••.•••• '369
A. N. Siakotos and D. Armstrong
V. Morphological changes in the nervous system in aging
18. Gross morphometric analyses and quantitative his-
tology of the aging brain •••••••••••••••.•••••••.•••• ~01
K. R. Brizzee
19. Changes in microanatomy, neurocytology and fine
structure with aging ••••••••••••••••••••••••••••••••• '425
K. R. Brizzee, P. KZara and J. E. Johnson
CONTENTS ix
20. Lipofuscin; intra- and extraneurona1 accumulation
and regional distribution ••••••••••••••••••••••••••• 463
K. R. B:r>izzee~ B. Kaaok and P. K"lrn>a
21. Changes in the neuronal microenvironment associated
wi th aging • • • • • • • • • • • • • • • • • • • . • . • • • • . • • • . • . • • . • • • • • • 485
W. Bondar>eff3 M. B:r>een and H. G. Weinstein
VI. Environmental modifiability or plasticity of the
brain and neuroendocrines from maturity to senescence
22. Effects of alcohol on aging in the nervous sys-
tem ..•.•••.•....••....•••..••.•.•••.•.••.••.••••.••• 505
A. Sun3 J. M. O:r>dy and T. Samo:r>ajski
23. Ionizing irradiation and aging •••••••••.•.••••••••.• 521
T. Samo:r>ajski
VII. Neuropathology and aging
24. Aging changes in relation to diseases of the
nervous system 545
K. R. B:r>izzee
VIII. Neurobiology and aging in nonhuman primates
25. Neurobiology and aging in nonhuman primates .•..•.••. 575
J. M. O:r>dy
IX. Index . .••.••.•.•••.•••...••••••..•••...••...••.......•••• 595
PRINCIPLES OF MAMMALIAN AGING
J. Mark Ordy, Head, Department of Neurobiology
Delta Regional Primate Research Center
Covington, Louisiana 70433
Fundamental Criteria, Data or Facts of Biological Aging. The
deterioration or "aging" of objects, animals and human beings with
the passage of time is one of the most universal, inevitable and
conspicuous features or characteristics observable in nature. With
the passage of time, changes occur in the properties, organization
or composition of all objects and living systems. The progressive
alterations with the passage of time can be imperceptible, gradual
and proceed at certain rates or they can become abrupt or sudden
and terminate in permanent change in state or "death" .as clearly
demonstrable "end points" of a system. The measurement of the
rates of gradual changes may be more difficult, particularly for
long-lived biological systems, even under steady-state environ
mental conditions. Consequently, such easily-recognizable end
points of biological aging as death and the ensuing mortality dis
tributions of a sample from a larger population are the most fre
quently used and convenient starting points or criteria of biolog
ical aging. If the end point in a sample from a population is
an abrupt change in state or death, the percentage of individual
members of an original sample remaining or surviving can be plot
ted statistically as a function of time. There are major demon
strable differences in the distribution curves of such end points
over chronological time between samples from populations of objects
or animals which do not age and those which do undergo changes
designated as aging or senescence. In samples from populations
that are not subject to aging but only random elimination or
death due to accidental causes, the decline in numbers from all
age groups is constant and logarithmic. The distribution curve of
such end points may have no relationship to an aging process. The
end points can simply be interpreted as the mean life expectancy
