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First published 1995 by CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
Reissued 2018 by CRC Press
© 1995 by Taylor & Francis
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T E
he ditor
Alvaro Macieira-Coelho, M.D., D.Sc., D.h.c., is Research Director at
the French National Institute of Health (INSERM), Department of Immu
nology, Medical School Pitié-Salpetrière, University of Paris VI.
Dr. Macieira-Coelho obtained his M.D. at the University of Lisbon,
Portugal and his D.Sc. from the University of Uppsala, Sweden. From
1958-1961 he was an intern at the Lisbon University Hospital and a
research associate at the Wistar Institute of the University of Pennsylvania
(1961-1964) and in the Department of Pathology of the University of
Uppsala (1964-1967). He was head of the Department of Cell Pathology at
the Institute of Cancerology and Immunogenetics, Villejuif, France (1967-
1986) and visiting professor at the Department of Cell Biology at the
University of Linköping, Sweden (1987-1989).
Dr. Macieira-Coelho currently teaches at the University of Paris. He
has given over 100 invited lectures at international meetings and at vari
ous institutes and universities, has published more than 100 research
papers, and is the author of one book. He was the editor of one book on
aging and is on the editorial board of four international gerontology
journals.
Dr. Macieira-Coelho received the Johananoff International Visiting
Professorship from the Mario Negri Institute (Milan) in 1982, the Fritz-
Verzaàr Prize for Gerontology from the University of Vienna in 1988, and
a Dr. Honoris Causa from the University of Linköping, Sweden, in 1991.
He is a member of the New York Academy of Sciences, American
Society for Cell Biology, American Association for Cancer Research, and
the Gerontological Society of America.
His current research interests concern the role of cell replication in
aging of the human organism, for which he received support from a grant
from the Sandoz Foundation for Gerontological Research.
C
ontributors
Paul S. Agutter, Ph.D. Siegfried Hoyer, M.D.
Department of Biological Sciences Department of Pathochemistry and General
Napier University Neurochemistry
Edinburgh, Scotland University of Heidelberg
Heidelberg, Germany
Hervé Allain, M.D., Ph.D.
Kenneth H. Johnson, M.D.
Pharmacology Laboratory
Department of Veterinary PathoBiology
Faculty of Medicine
College of Veterinary Medicine
University of Rennes I
University of Minnesota
Rennes, France
St. Paul, Minnesota
Fiorenzo Battaini, Ph.D. M. S. Kanungo, Ph.D.
Department of Experimental Medicine and Molecular Biology Laboratory
Biochemical Sciences Department of Zoology
University of Rome Tor Vergata Banaras Hindu University
Rome, Italy Varanasi, India
and
Danièle Bentue-Ferrer, Ph.D. Institute of Life Sciences
Bhaneswar, India
Pharmacology Laboratory
Faculty of Medicine Paul J. M. Klosen, Ph.D.
University of Rennes I Laboratory of Cell Biology
Rennes, France Catholic University of Louvain
Louvain-la-Neuve, Belgium
Philippe van den Bosch de Aguilar,
J. Labat-Robert, Ph.D.
Ph.D.
Department of Cell Biology
Laboratory of Cell Biology
University of Paris VII
Catholic University of Louvain
Paris, France
Louvain-la-Neuve, Belgium
Hans U. Lutz, Ph.D.
Ulf Brunk, Ph.D. Laboratory for Biochemistry
Department of Pathology Swiss Federal Institute of Technology
University of Linköping Zurich, Switzerland
Linköping, Sweden
Alvaro Macieira-Coelho, M.D., D.Sc.,
D.hc.
James W. Gaubatz, Ph.D.
Research Director, INSERM
Department of Biochemistry and Molecular
Versailles, France
Biology
College of Medicine Jaime Miquel, Ph.D.
University of South Alabama
Chief, Division of Applied Neuroscience
Mobile, Alabama
Institute of Neurosciences
University School of Medicine
Stefano Govoni, Ph.D. Alicante, Spain
Institute of Pharmacological Sciences and
University of Milan Institute of Molecular Medical Sciences
Milan, Italy Palo Alto, California
Werner E. G. Müller, Ph.D. George S. Roth, Ph.D.
Department of Applied Molecular Biology Molecular Physiology and Genetics Section
Institute of Physiological Chemistry Laboratory of Cellular and Molecular Biology
Mainz, Germany Gerontology Research Center
NIH, National Institute on Aging
Atsushi Miyamoto, M.S., Ph.D. Baltimore, Maryland
Department of Pharmacology
Heinz C. Schröder, M.D., Ph.D.
Sapporo Medical University School of
Medicine Department of Applied Molecular Biology
Sapporo, Japan Institute of Physiological Chemistry
Mainz, Germany
Hans Niedermüller, Ph.D.
D. F. Swaab, M.D., Ph.D.
Austrian Society for Geriatrics and
Director, Graduate School Neurosciences
Gerontology
Netherlands Institute for Brain Research
Institute of Physiology
Amsterdam, The Netherlands
and
The Ludwig Boltzmann Institute of
Marco Trabucchi, M.D.
Experimental Gerontology
Department of Experimental Medicine and
Veterinary Medical University
Biochemical Sciences
Vienna, Austria
University of Rome Tor Vergata
Rome, Italy
Suresh I. S. Rattan, Ph.D., D.Sc.
Laboratory of Cellular Aging Per Westermark, M.D., Ph.D.
Department of Chemistry
Department of Pathology
Aarhus University
Linköping University
Aarhus, Denmark
Linköping, Sweden
Ladislas Robert, M.D., Ph.D. Dazhong Yin, Ph.D.
Department of Cell Biology Department of Pathology
University of Paris VII Linköping University
Paris, France Linköping, Sweden
J. N. Zhou, M.D.
Graduate School Neurosciences
Netherlands Institute for Brain Research
Amsterdam, The Netherlands
and
Ningxia Medical College
Ningxia, China
T C
able of ontents
Introduction....................................................................................................1
I. THE STORAGE OF INFORMATION
Chapter 1
Reorganization of the Genome during Aging of Proliferative Cell
Compartments..............................................................................................21
Alvaro Macieira-Coelho
Chapter 2
Genomic Instability during Aging of Postmitotic Mammalian Cells...............71
James W. Gaubatz
Chapter 3
DNA Repair during Aging...........................................................................137
Hans Niedermiiller
Chapter 4
Changes in Gene Expression during Aging of Mammals.............................183
M. S. Kanungo
Chapter 5
Role of Mitochondria in Cell Aging..............................................................219
Jaime Miquel
II. THE FLOW OF INFORMATION
Chapter 6
Modifications of the Cell Surface Leading to Cell Elimination......................237
Hans U. Lutz
Chapter 7
Protein Kinase C Signal Transmission during Aging....................................269
Fiorenzo Battaini, Stefano Govoni, and Marco Trabucchi
Chapter 8
Changes in Transmembrane Signaling Mechanisms during Aging:
Cellular and Molecular Aspects...................................................................293
Atsushi Miyamoto and George S. Roth
Chapter 9
Structural Changes Modifying the Intracellular Flow
of Information..............................................................................................307
Alvaro Macieiro-Coelho
Chapter 10
The Aging of the Neuronal Cytoskeleton......................................................327
Paul J. M. Klosen and Philippe van den Bosch de Aguilar
Chapter 11
Transport of mRNA into the Cytoplasm......................................................353
Werner E. G. Mittler, Paul S. Agutter; and Heinz C. Schroder
Chapter 12
Translational and Post-translational Modifications during Aging.................389
Suresh I. S. Rattan
Chapter 13
Carbonyl Toxification Hypothesis of Biological Aging..................................421
Dazhong Yin and Ulf Brunk
Chapter 14
Amyloidosis and Aging...............................................................................437
Per Westermark and Kenneth H. Johnson
Chapter 15
Extracellular Matrix......................................................................................459
Ladislas Robert and J. Labat-Robert
Chapter 16
Brain Metabolism during Aging...................................................................493
Siegfried Hoyer
Chapter 17
Central Neurotransmission in the Elderly.....................................................511
Hervé Allain and Daniele Bentue-Ferrer
Chapter 18
Age-Related Changes in Neuropeptidergic Neurons in the
Human Hypothalamus.................................................................................527
J. N. Zhou and D. F. Swaab
Index............................................................................................................533
I
ntroduction
Those without expertise in gerontology, but interested in understand
ing the investigations carried out to elucidate the mechanisms of aging,
face many difficulties.
PROBLEMS ARISING FROM COMPARATIVE BIOLOGY
AND PHYSIOPATHOLOGY
One difficulty comes from the tendency that many gerontologists
have of looking for a global view of the mechanisms of aging along the
evolutionary scale, extrapolating data, and then seeking for universal
explanations. Comparative biology has shown that the mechanisms of
aging cannot be universal.1 This does not mean, however, that studies
performed on lower organisms along the evolutionary scale are useless in
understanding human aging. Some mechanisms may be conserved, but as
an organism becomes more complex other regulatory mechanisms come
into the picture, and as a result the homeostatic regulation of the life span
also increases in complexity. Moreover, along the evolutionary road some
mechanisms have remained preponderant in some species, while becom
ing secondary in others.
It is obvious that the mechanisms controlling the life span in Droso
phila, for instance, where there is no cell turnover in the mature organism,
cannot be the same as those in a mammal, where permanent renewal
occurs throughout the life span in many cell compartments, and whose
genome is more complex than that of a fly. Initial mortality rates are also
extremely high in flies; as compared with humans, they are 1000 times
higher.1 This illustrates fundamental developmental differences, showing
that the mechanisms regulating the life span in Drosophila cannot be
extrapolated to vertebrates.
A disregard for comparative biology and physiopathology has led to
shortcuts and misinterpretations that have retarded the advancement of
gerontology and handicapped communications between gerontologists.
We have limited this volume to experimental approaches performed
with mammals but even among mammals striking differences appear,
indicating that extrapolations should be carried out with restraint.
1
