Neuroregulatory Mechanisms in Aging PDF
Preview Neuroregulatory Mechanisms in Aging
Pergamon studies in neuroscience No 8 Series editor Or William Winlow, Dept of Physiology, University of Leeds, LS2 9NQ, UK Neuroscience is one of the major growth areas in the biological sciences and draws both techniques and ideas from many other scientific disciplines. Pergamon studies in neuroscience presents both monographs and multi-author volumes drawn from the whole range of the subject and brings together the subdisciplines that have arisen from the recent explosive development of the neurosciences. Pergamon studies in neuroscience includes contributions from molecular and cellular neurobiology, developmental neuroscience (including tissue culture), neural networks and systems research (both clinical and basic) and behavioural neuroscience (including ethology). The series is designed to appeal to research workers in clinical and basic neuroscience, their graduate students and advanced undergraduates with an interest in the subject. 1. Function and dysfunction in the basal ganglia ed. A. J. Franks, J. W. Ironside, R. H. S. Mindham, R. J. Smith, E. G. S. Spokes and W. Winlow 2. Comparative aspects of neuropeptide function ed. Ernst Florey and George B. Stefano 3. Neuromuscular transmission: basic and applied aspects ed. Angela Vincent and Dennis Wray 4. Neurobiology of motor programme selection: new approaches to the study of behavioural choose ed. Jenny Kien, Catherine R. McCrohan and William Winlow 5. lnterleukin-1 in the brain ed. Nancy J. Rothwell and Robert D. Dantzer New in 1993 A theory of the striatum J. Wickens Glycobiology and the brain ed. M. Nicolini and P. F. Zatta Neural modeling and neural networks ed. F. Ventriglia Neurophysiology of Ingestion ed. D. A. Booth Neuroregulatory mechanisms in aging ed. Maynard H. Makman and George B. Stefano Thalamic networks for relay and modulation ed. Diego Minciacchi, Marco Molinari, Giorgio Macchi and Edward G. Jones Neuroregulatory Mechanisms in Aging edited by Maynard H. Makman and George B. Stefano PERGAMON PRESS OXFORD· NEW YORK· SEOUL· TOKYO U.K. Pergamon Press Ltd, Headington Hill Hall, Oxford 0X3 OBW, England U.S.A. Pergamon Press, Inc., 660 White Plains Road, Tarrytown, New York 10591-5153, U.S.A. KOREA Pergamon Press Korea, KPO Box 315, Seoul 110-603, Korea JAPAN Pergamon Press Japan, Tsunashima Building Annex, 3-20-12 Yushima, Bunkyoku, Tokyo 113, Japan Copyright © 1993 Pergamon Press Ltd All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise, without permission in writing from the publishers. First edition 1993 Library of Congress Cataloging in Publication Data A catalogue record for this book is available from the Library of Congress British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 08 041989 5 In order to make this volume available as economically and as rapidly as possible it has been produced by translation from the authors' word processor disks. Every effort has been made to ensure an exact reproduction within the time available. Printed in Great Britain byBPCC Wheatons Ltd, Exeter List of Contributors S. BHATNAGAR Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada T. V. BILFINGER Department of Surgery, Health Science Center, University Hospital, SUNY at Stony Brook, Stony Brook, NY 11794, USA P. BLANCO Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain R. J. BODNAR Department of Psychology, Queens College, Flushing, New York, USA S. R. BODNOFF Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada E. BOGONEZ Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain D. O. CARPENTER Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany, New York 12201-0509, USA E. E. EL-FAKAHANY Department of Pharmacology and Toxicology, University of Maryland, School of Pharmacy, Baltimore, MD 21201, USA vii viii List of Contributors G. L. FRICCHIONE Brigham's Womens Hospital, Division of Psychiatry, Harvard Medical School, Boston, Mass., USA I. HIROTSU Laboratory of Experimental Pharmacology, Suntory Institute for Biomedical Research, 1-1-1, Wakayamadai, Shimamoto-Cho, Mishima- Gun, Osaka 618, Japan N. HORI Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany, New York 12201-0509, USA and Department of Pharmacology, Faculty of Dentistry, Kyushu University, 1-1-3, Maidashi, Higashi-Ku, Fukuoka 812, Japan C. JANSE Department of Biology, Vrije Universiteit, 1007 MC, Amsterdam, The Netherlands J.A.JOSEPH Molecular Physiology and Genetics Section, Gerontology Research Center/NIA, Baltimore, MD 21224, USA N. KATSUDA Department of Pharmacology, Faculty of Dentistry, Kyushu University, 1-1-3, Maidashi, Higashi-Ku, Fukuoka 812, Japan M. H. MAKMAN Departments of Biochemistry and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA L. MALLOZZI Multidisciplinary Center for the Study of Aging, State University of New York/College at Old Westbury, Old Westbury, New York 11568, USA A. MARTINEZ-SERRANO Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain List of Contributors ix M.J.MEANEY Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada D. O'DONNELL Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada G. W. PASTERNAK The George C. Cotias Laboratory of Neuro-Oncology, Memorial Sloan- Kettering Cancer Center and Department of Neurology and Neuroscience, Department of Pharmacology, Cornell University Medical College, New York 10021, USA J. POIRIER Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada S. PRYOR Multidisciplinary Center for the Study of Aging, State University of New York/College at Old Westbury, Old Westbury, New York 11568, USA P. G. PUERTAS Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain J. SATRUSTEGUI Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain G. B. STEFANO Old Westbury Neuroscience Institute and Multidisciplinary Center for the Study of Aging, State University of New York/College at Old Westbury, New York 11568-0210, USA x List of Contributors M. VILLALBA Departamento de Biologia Molecular (CSIC-UAM), Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain S. A. WELNER Aging Research Program, McGill University-Douglas Hospital Research Center, Departments of Psychiatry, Neurology and Neurosurgery and Experimental Medicine, McGill University, Montreal, Canada Introduction and Perspectives on the Neurobiology of Aging MAYNARD H. MAKMAISM and GEORGE B. STEFANO2 1 Departments of Biochemistry and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA 2 Old Westbury Neuroscience Institute and Multidisciplinary Center for the Study of Aging, State University of New York/ College at Old Westbury, New York 11568-0210, USA Studies of aging have generally been concerned with determinants of life span and cause of death, decreases in proliferative capacity of different cell types, and functional impairments associated with old age. An additional major consideration, of particular relevance to aging of the nervous system, is the existence of and interaction between "normal" aging and specific disease states that are more likely to occur with increased age. The nature and extent of changes that occur with increasing age may differ considerably in different species and also in the various organs or tissues of a given species. Functionally important age-related changes may or may not also be important causes of death of the animal. In addition, a particular age-related pathological process may be unique to one species or to a group of animal species. On the other hand, important features of senescence may be shared by different animals, and indeed there may be aspects of aging that are shared by both vertebrate and invertebrate species. There may be certain animals that do not appear to age, e.g., certain paramecia and bivalve molluscs. However, it is possible that even those animals age, but they also have an extremely long natural life span. We may not see each individual organism age simply because of the occurrence of accidental death. The concept of negative pleiotropy has been employed to account for biological senescence. Indeed, cumulative and unavoidable events or reactions may eventually lead to decrements in function and/or death of an organism. Hence, oxygen-free radicals, advanced glycosylation endproducts, protein adducts, damage occurring with genetic repair, etc., may accumulate to critical levels at which normal functions are compromised. 1 2 M. H. Makman and G. B. Stefano Furthermore, the causative factor may even be a once useful process now occurring in excess. Over time molecular alterations may pyramid into cellular, tissue, organ and organismal modifications /compensations whereby an individual will exhibit a general decline in function and reactive capacity. Such age-associated modifications, at least certain of them, are essentially inevitable. Also, by such processes alterations that continue to occur may eventually allow the organism to succumb to an environmental assault which at an earlier time posed no threat. Thus, the aging process may insure for enhanced vulnerability and death of a particular organism, thereby allowing for turnover of the population and the possibility for incorporation of useful mutations into the population. In the human population there is evidence of age-related decrements in central nervous system (CNS) function, including behavioral impairment and altered response to CNS drugs. Certain of these decrements may apply to the general human population and be due to selective age-related alterations in neurotransmitter systems that also occur with aging in other mammalian species. However, there may be no close counterpart in other species to senile dementia of the Alzheimer's type, a human disease associated with, and possibly caused by, loss of certain central cholinergic neurons. It is often difficult to be certain in studies of human aging whether or not particular age-related changes represent "normal" aging due to factors intrinsic to the organism or unavoidable interactions with the environment, or to specific disease processes that may be as yet undefined. However, it appears likely, based on animal studies, that age-associated changes in CNS neurotransmitter systems indeed occur independent of any specific disease process. These changes may be manifest in altered function per se, altered functional "reserves" and/or altered predisposition to or severity of pathological processes. Not all functional components or neuronal cell types are affected similarly by the aging process. Probably in most instances the underlying cause(s) for a particular change is (are) not known. The degree of plasticity of the adult nervous system is only now beginning to be appreciated. Also, the possible regenerative capacity in some situations remains to be evaluated. Additionally, changes in these parameters with aging remain to be investigated. The chapters in this book present studies of neuronal aging in a variety of species. Also, a variety of approaches are utilized in order to gain insight into the nature and significance of age-related changes. The overall intent is to present some indication of the wide scope of these studies, to give some idea of the present state of knowledge of the neurobiology of aging in selected areas, and to include Neurobiology of aging 3 representative examples of approaches and "model systems" for such studies. We believe the comparative biological aspect to be of particular importance. The comparative study of neuronal aging greatly enhances our knowledge of the functioning of animal species that may be quite different from one another, yet contain nervous systems with many similarities with respect to their transmitter systems as well as the basic sensory, motor and integrative functions. These studies reveal surprising similarities in the integrative processes regulating function and the life cycle in mammals and invertebrates. Comparative studies of neuronal aging may also serve to focus attention on those aspects of neuronal processes and adaptive mechanisms that are necessary for survival and propagation of the organism. For these reasons, such studies have a general relevance to our understanding of life cycle events and the aging process in all living organisms. Since molecular biology has not yet provided the means for intervention in the aging process, at present we are left with the pharmacological approach to alleviate some of the effects of aging and to restore age-associated alterations of normal function. Given the vast amount of information that has been accumulated concerning the pharmacology of the nervous system, it becomes important to attempt to use this information to intervene appropriately in the aging process. Also, age-related changes in the responses of humans to CNS-active drugs have provided significant clues to the possible underlying changes in the nervous system that occur with age. For these reasons, neuropharmacological studies have provided a major focus for this book. Clearly, the nervous system plays a central role in the integrative dynamic responsiveness of the organism. At the cellular and molecular levels, modifications associated with damage or aging can be masked by a host of compensatory mechanisms. However, once the utilization of a particular compensatory mechanism reaches a point at which no further change in the mechanism is possible or at which no further response of the organism to that mechanism is possible, then the functioning of the organism is compromised. A characteristic feature of aging appears to be an altered, generally decreased, intrinsic or adaptive response, including decreased reliability of homeostatic regulation. In this regard, the role of the nervous system is particularly important since it may be the first system to "signal" a decrease in the dynamic capacity to respond. The integrative functions of the nervous system include not only the obvious hard wiring, including direct innervation of peripheral tissues, but also a sort of soft wiring that allows for bidirectional
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