Aging and Life-Prolonging Processes

387 Pages·1982·12.47 MB·English

by  Prof. Dr. Vladimir Veniaminovich Frolkis (auth.)

Aging and
Life-Prolonging
Processes
Prof. Dr. Vladimir Veniaminovich Frolkis
Corresponding Member of the Academy of Sciences of the UkrSSR
Institute of Gerontology of the Academy of Medical Sciences of the USSR
Kiev, USSR
Nicholas Bobrov
Moscow, USSR
This work is subject to copyright.
All rights are reserved, whether the whole or part of the material is concerned,
specifically those of translation, reprinting, re-use of illustrations, broadcasting,
reproduction by photocopying machine or similar means, and storage in data banks.
© 1982 by Springer-Verlag Wien
Softcover reprint of the hardcover 1st edition 1982
With 91 Figures
Library of Congress Cataloging in Publication Data. Frolkis, V. V. (Vladimir Veniaminovich).
Aging and life-prolonging processes. 1. Aging. 2. Neuroendocrinology. 3. Longevity. I. Title.
QP86.F736. 1982. 612.67. 82-19211
ISBN-13: 978-3-7091-8651-0 e-ISBN-13: 978-3-7091-8649-7
DOl: 10.1007/978-3-7091-8649-7
Preface
There is an Inca incantation which stated said roughly: "Lord, give me
spiritual peace so that I can acquiesce to what I cannot change, give me courage
so that I can change what I can change, and give me wisdom so that I can
distinguish one from the other."
Obviously, this incantation can be regularly repeated by any gerontologist,
since it is very difficult to distinguish aging from the processes which enhance
the organism's viability, aging from diseases, and the mechanisms of aging in
various species of animals.
According to N. Shock, who compiled a valuable bibliography of the works
on aging, more than 43,000 works on gerontology have been published in the
last decade. Why do we continue to disagree with one another and hold that the
most important mechanisms are still largely unknown to us in spite of that flow
of information and an enormous number of facts? What is it that we do not
know? Could it be that we do not know the sole sacramental fact which can
explain everything, such as the hormone of aging, the programmed triggering of
a suicide gene, the appearance of a special toxic agent in the axoplasmic flow of
substances, and so forth?
Goethe once wrote that a scientist most often holds certain parts, but
unfortunately he lacks their sacred link. It could be that what is most important
is a one-sided idea of the essence of the processes which occur during individual
development and the fact that we still have not established a cause-consequence
relationship in the enormous amount of the known changes which occur with
age, that we do not know the temporal sequence of their development, that we
do not correctly assess them quantitatively, and that we do not always know
what is primary and what is secondary. Apparently, all this is important. We
still do not know much about the manifestations of aging, and what we do
know, we cannot link together.
Therefore, in gerontology, it is important to make a systemic approach,
which is not confined to a description of what occurs at various levels of the
organism's vital activity, but unites the occurrences into a single system, and to
analyze the mechanisms of aging from the standpoint of self-regulation.
Regulation, adaptation and aging are three categories. They are three extremely
complicated biological processes. The biological essence, principle and direction
of the organism's aging can be understood from the standpoint of the
relationship between these processes.
VI Preface
Classical gerontology reveals the mechanisms of aging that are connected
with the appearance, accumulation and action of the inevitable damaging factors.
However, it is important to make a fundamental approach, i. e. to study the
processes which make the live systems stable, so as to understand the
mechanisms which determine the life span, aging, and the diminution of the
organism'S adaptive abilities with age.
Making that approach, the author of this book asserts that life-prolonging
processes exist. Vitauct (from the Latin words "vita", meaning life, and
"auctum", meaning to prolong), which stabilizes the organism'S viability and
increases the life span, occurs together with aging, a destructive process, during
individual development. The inseparable link between vitauct and aging
determines both development with age and the life span. The next stage of
gerontology will largely involve an analysis of the parameters and mechanisms
of vitauct that make it possible to maintain vital activity when the damaging
factors inevitably act. In this book, the author describes the relationship
between aging and vitauct, ascertains the role which the neurohumoral
mechanisms play in their development, and then discusses the possible ways of
increasing the life span.
Kiev, September 1982 v. V. Frolkis
Contents
1. General Biology of Vitauct and Aging .................................. .
Vitauct and Aging ....................................................... .
General Regularities of Aging .............................................. 14
Mechanisms of the Life Span of a Species ..................................... 20
Aging and Evolution ...................................................... 27
Aging and Diseases ....................................................... 30
2. Aging of the Brain .................................................... 33
General Direction of the Age Changes in the Brain ............................ 33
Structural and Metabolic Changes in the Brain During Aging .. . . . . . . . . . . . . . . . . . . 36
Change in the Brain Functions with Age ..................................... 52
3. Hypothalamohypophysial Regulation During Aging ...................... 70
Regulatory Effects of the Hypothalamus ..................................... 70
Hypothalamohypophysial Influences ........................................ 79
Mechanisms of Vasopressin Regulation ...................................... 83
Feed-backs in the System of Hypothalamohypophysial Regulation in Old Age. . . .. 87
Adaptive Reactions of the Hypothalamus in Old Age .......................... 91
4. Adrenergic Mechanisms of Regulation During Aging ..................... 99
Effects of the Adrenergic Influences in Old Age ............................... 100
Sympathetic Ganglia During Aging .......................................... 109
Catecholamine Metabolism ................................................ 113
5. Cholinergic Mechanisms of Regulation During Aging ..................... 124
Acetylcholine Metabolism ................................................. 124
Effects of Cholinergic Influences ............................................ 135
6. Insulin Provision of the Organism During Aging ......................... 139
Content of Insulin and Carbohydrate Tolerance ............................... 140
Structural and Functional Changes in the Insular Apparatus ..................... 147
Specifics of the Tissue Reaction to the Action of Insulin in Old Age .............. 150
Regulatory Mechanisms of Insulin Provision .................................. 152
Influence of the Change in Insulin Provision on Metabolism .................... 154
7. Thyroid Regulation in Old Age ......................................... 157
Structural and Functional Changes in the Thyroid Gland ....................... 157
Thyroid Hormones in the Blood ............................................ 163
Hypothalamohypophysial Regulation of the Thyroid Gland Function ............ 166
Specifics of the Influence of Thyroid Hormones on Tissue in Old Age ............ 170
Feed-back Control of the Thyroid System .................................... 173
Specifics of the Reactions of the Thyroid Control System ....................... 175
8. Neural Regulation of Tissue Trophism in Aging .......................... 179
VIII Contents
9. Local Mechanisms of Humoral Regulation During Aging .................. 194
Cyclic Nucleotides ....................................................... 194
Adenosine Metabolic System ............................................... 196
Kallikrein-Kinin System ................................................... 198
Serotonin ................................................................ 201
Prostaglandins ........................................................... 202
10. Neurohumoral Mechanisms of the Regulation of the Genetic Apparatus ... 205
Genoregulatory Hypothesis of the Processes of Vitauct and Aging ............... 205
Hormonal Regulation of the Genetic Induction of Enzymes .................... 214
Hypothalamohypophysial-Adrenal System of the Regulation of the Genetic Appara-
tus ..................................................................... 225
11. Neurohumoral Regulation of the Energy Processes ...................... 230
Oxidative and Glycolytic Phosphorylation During Aging ....................... 230
Hormonal Mediatory Influences on the Energy Processes ....................... 242
12. Neurohumoral Mechanisms of Cellular Aging ........................... 252
Sequence of Cellular Aging ................................................ 252
Membranogenetic Mechanisms of Cellular Aging .............................. 264
Electric Properties of Cells During Aging .................................... 274
13. Neurohumoral Regulation of the Cardiovascular System ................. 280
Hemodynamics and Age ................................................... 280
Hemodynamic Centre in Aging ............................................. 286
Efferent Neurohumoral Regulation of the Cardiovascular System ................ 288
Reflexes of the Cardiovascular System ....................................... 298
Regulation of Coronary Blood Circulation in Old Age ......................... 303
14. Experimental Life Prolongation ........................................ 306
Criteria of the Life Span ................................................... 307
Influence of Physical, Chemical and Biological Factors on the Life Span ........... 314
Influence of Physical Factors on the Life Span ................................ 314
Temperature ......................................................... 314
Influence of Temperature on the Life Span of Warm-Blooded Animals ........ 320
Influence of Ionizing Radiation on the Life Span ........................... 322
Influence of the Electric and Magnetic Fields on the Life Span ............... 324
Influence ofthe Chemical Factors on the Life Span ............................ 324
Influence of Microelements and Chelating Agents on the Life Span ........... 325
Influence of Antioxidants on the Life Span ................................ 326
Influence of the Stabilizers of the Lysosomal Membranes on the Life Span ..... 326
Influence of Latirogens on the Life Span .................................. 327
Influence of Other Chemical Agents on the Life Span ...................... 328
Influence of the Biological Factors on the Life Span ............................ 328
Influence of the Low-Calorie or Low-Protein Diet on the Life Span .......... 328
Influence of Physical Activity on the Life Span ............................ 332
Influence of the Hormones on the Life Span .............................. 333
Influence of the Inhibitors of Protein Biosynthesis and Energy Metabolism on
the Life Span ......................................................... 335
Influence of the Genetic Factors on the Life Span .......................... 338
In Lieu of a Conclusion ................................................... 341
References .............................................................. 345
Subject Index ............................................................ 378
1. General Biology of Vitauct and Aging
Vitauct and Aging
Gertsen, a nineteenth century Russian writer, wrote that scientists had come
so close to the "shrine of nature" that they sometimes saw only what was before
their very eyes. He regarded this as one of the reasons why natural phenomena
were interpreted in a one-sided, individual and occasionally erroneous way. The
danger of doing this is especially great in gerontology today, because much
factual material on the biology of aging has been collected during only the last
few decades.
Hence, it is especially important to correctly understand the essence of aging
in the general biological sense. Definite mechanisms of aging may be interpreted
incorrectly and the significance of aging as well as the development of living
matter in a person's life and death may be defined incorrectly if errors are made
in this respect. Such errors engender an extreme, likewise erroneous attitude
towards controlling the aging process. This attitude may range from the
complete rejection of the possibility of controlling the process to an inadequate,
light-minded view on the life span, giving rise to promises to greatly prolong a
person's life in the immediate future. Today, gerontology is not only a field
where disputes are held on the existence of various aging mechanisms, but also a
battlefield where views clash. Indeed, vulgar materialistic views on the essence
of aging, which almost completely identify the aging and destruction of
inanimate objects with the very complicated biological process of aging, and also
idealistic views on the existence of "entelechy," "creative energy" and an
unknowable beginning, the exhaustion of which causes aging, are being asserted
and developed even today. Interestingly many authors of such concepts took a
strictly scientific, objective, factual stand in their creative work, but when they
go down to biological generalizations, they regarded unexplained facts as
something inexplicable. This approach often leads to idealism, which in essence
incapacitates a researcher and turns facts which have not been understood into
something unknowable.
In gerontology, many facts are now known about a change in various
parameters of the organism during individual development and aging. Some
parameters progressively decrease when maturity is reached (they include indices
of higher nervous activity, the function of analyzers, mental and physical
working ability, the secretory activity of the sexual, thyroid and digestive
glands, myocardial contractility, and the number of cells). Others do not change
substantially by old age (the blood sugar level; some indices of the acid-base
1 Frolkis, Aging
2 General Biology of Vitauct and Aging
balance, the morphological composition of blood, namely, the number of
erythrocytes, leukocytes and thrombocytes, the membrane potential of many
cells, the activity of some enzymes, etc.), while still others increase (the
synthesis of some pituitary hormones, the sensitivity of some tissues to
hormones, the activity of some enzymes, arterial pressure, the blood contents of
globulin, cholesterol, lecithin and beta-lipoproteins, etc.). Such a non-uniform
change in the biological parameters is characteristic of ontogeny as a whole
(Fig. 1). Development should be regarded as homeorhesis, which is the course
of a change in a system with respect to time. Homeostasis is a stabilized state,
while homeorhesis is stabilized flow. What determines the very complicated
interaction between the diversely directed, but not chaotic changes and what
links them together in age homeorhesis? How do these changes create a live
system and maintain its existence, and when do they transcend the bounds of its
possible development? Can this seeming diversity be explained by simply stating
that an organism at first develops and becomes perfect, and then all the
processes occur in the opposite direction, i. e. involution, or regressive
development? These questions as well as many others arise when an effort is
made to explain the essence of phenomena which occur as the organism ages.
time-
Fig. 1. Dynamics of the age changes of various biological parameters during ontogeny
However, there is a principle which explains how a chance occurrence has
become a law, how the initial manifestations of life combined into very intricate
biological systems, including man, how all this diversity is incorporated in the
viability of the organism, and why there are two opposite tendencies in
historical and individual development: vitauct and aging. This is a principle of
self-regulation. All the levels of biological organization are self-regulatory ones.
However, the organism as a whole is a single self-regulating system, and one of
its aspects (neurohumoral mechanisms) controls other levels of biological
hierarchy. In this respect, it should be noted that the viability of the organism
decreases as it grows old, when the disturbances which occur with time are not
compensated by the mechanisms of self-regulation. Owing to these mechanisms,
the biological system becomes perfectly adapted to the living conditions at all
the levels of biological organization, and an extremely important aspect of life,
Vitauct and Aging 3
i. e. the activation of the processes of restoration, is ensured. If the whole life
cycle is nominally divided according to this principle, it can be assumed that
restoration with supercompensation occurs in early ontogeny, i. e. during the
period of growth, restoration with compensation occurs in maturity, and
restoration with decompensation occurs in late ontogeny.
Today, the keen interest taken in the problem of aging, being among the
cardinal problems in modern science, is not merely an expression of mankind's
aspiration to understand the meaning of aging and to influence its course. This
aspiration always existed.
Science is developing in accordance with certain laws, and every stage of its
development has its own historical prerequisites. Even the most brilliant
predictions are based on the achievements of the previous generations.
Biological achievements, i. e. the discovery of the essence of the transmission of
hereditary information, protein biosynthesis, successes in cytology, and the
discovery of the most important laws of regulating the living, have become the
basis of the new, really revolutionary stage in the development of gerontology.
Researchers are paying more and more attention to gerontology also because of
some socio-economic factors, including an extremely important phenomenon of
this century, i. e. the aging of the population of the developed countries and the
growth of the share of elderly and old people in the overall population structure.
Statisticians predict that the Soviet Union will have 50 million people of
pensionable age in the 1980's and 80 million people by the year 2000. In 1970,
15.9 per cent of the population of Hungary, 18.0 per cent of the population of
Great Britain and 28.7 per cent of the population of the German Democratic
Republic were above the age of 60. Never has the mean life span been so high
and the problem of the position of elderly people in society as well as their role
in the economy so acute as now. As the number of elderly and old people
increases, the state must make greater outlays on social security, and new labor
sources must be found. Such an increase affects the entire public health system,
because more medical care must be given to these people. Thus, researchers are
taking interest in gerontology for not only strictly scientific, academic and
cognitive, but also practical reasons.
The history of gerontology is interesting and instructive. Gerontology
developed on the basis of definite achievements in the major sciences. As the
conception of the endocrine glands rapidly developed at the end of the last
century, it was argued that a change in their activity was decisive in the genesis
of aging. By thoroughly studying the structure and functions of the cells and
elaborating the methods of investigating tissue cultures, it became possible to
work out the concepts of a link between the ability of the cells to undergo
division and their aging. Molecular genetic hypotheses of aging originated as it
became more or less clear how hereditary information was transmitted and how
protein underwent biosynthesis.
The formation and development of gerontology are associated with such
names as Mechnikov, Bogomolets, Nagorny and Verzar. They all understood
the given process and its role in the life of an individual and society after
thoroughly studying the essence of phenomena. Their prestige in other fields of
natural science has helped to draw some researchers' attention to gerontology.