General system theory of aging
Special role of the immune system
V. I. Dontsov
© V. I. Dontsov, 2019
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V.I. Dontsov.General system theory of aging. Special role of the immune system. 2019. 320 p. Electronic edition. Figures 57. Schemes 4. Tables 4. Formulas 9.
Translation from Russian by the service of Springer Edit.
The monograph examines the general methodological problems of the aging of biological systems, debunking myths and cliches circulating in this area; modeling of the general aging process, highlighting the causes of aging, the main mechanisms, and their biological content, as well as consideration of the fundamental possibilities and directions of influence on this process.
A special place is occupied by the use of system analysis and consideration of integrative systems that combine hierarchically complex systems into a single whole, and the special role of the immune system, namely, that part of it, which is not responsible for immune phenomena proper, but regulates the interaction of various cell populations in the body. A single look at aging allows you to determine the possibilities and directions of influence on this process, and the allocation of aging syndromes, similar to those in common diseases, allows you to influence aging with conventional therapeutic agents.
The book is intended for specialists in the field of general biology and medicine, system analysis, for gerontologists and specialists in anti-age medicine and biology of aging, as well as for graduate students, teachers, and students of higher educational institutions, theorists and experimental studies.
Introduction
According to WHO, the level of health and life expectancy of the population are among the central indicators of the level and quality of life in the country. However, the increase in life expectancy, which is universally observed in all civilized countries, poses a serious problem associated with a simultaneous decrease in the birth rate, this is a worldwide trend of aging of the population. The problem of aging is occupied by the most diverse areas of theoretical science and their practical sections. General biology considers the emergence and evolution of ontogenesis, the species life span, the ecology of species and the Earths overall ecosystem.
Demography develops population gerontology, especially the aging of various population groups and the change in mortality in different historical epochs. Molecular biology, genetics, physiology, biochemistry, and histology have thoroughly studied all the features of the manifestation of aging at the level of molecules, genes, cells, tissues and organs, as well as changes in the systemic relationships of organs and tissues in the whole organism throughout life. Geriatrics studies in detail the course and treatment of diseases in the elderly.
However, it is philosophy, its methodological section gnoseology, and the modern methodological scientific principle system analysis that plays a leading role in questions about the essence of life and death, constant movement and self-renewal, and also in methodological questions about the essence and cause of the aging phenomenon and the fundamental possibility of overcoming it, about the future of man as a race with global interventions in the biological nature of man and in other generally significant, human-common problems.
Knowledge of philosophy and methodology eliminates the typical flaws characteristic of modern representatives of highly specialized science, first of all, of replacing the essence of aging with its mechanisms, which led to the unrestrained reproduction of the theories of aging.
Practical success is always based on new scientific knowledge and theoretical work, which is especially important for the science of aging. In recent years, quite a lot of fundamental work has appeared on molecular, genetic, cellular manifestations of aging, and ideas about the role of apoptosis, telomerase and other relatively new scientific data on cellular processes in aging processes are being exaggerated. At the same time, no clear idea of aging as a single process affecting the whole organism is formed. It is not clear how important the studied mechanisms of aging are for the aging of the whole organism, how they interact with each other and how important they are.
In this monograph, using the system analysis methodology, to consider the aging process as a whole as a phenomenon typical of all living things, as well as to highlight the most important aging processes and mechanisms for mammals and humans first of all.
We also present a new look at the main mechanisms of aging associated with the development of regulatory models of aging and specifying their manifestation through the immune mechanisms, and the immune mechanisms here act in a specific form as regulators of the proliferative activity of somatic cells, which is pronounced decreases with age, defining age-related atrophy of tissues this is a new trend in immunobiology, in which domestic scientists are ahead in the world.
The monograph makes it possible in general to create a general idea of aging, its causes and main mechanisms, and to evaluate the possibilities and ways of influencing, having a clear idea about the points of application and the possible effectiveness of effects, which is always the main complexity of modern theories and practical impacts on aging.
Main Points
The presence of hundreds of theories of aging to date indicates not only and not so much the lack of a unified theory, general views, or lack of knowledge of the causes and essence of aging, but often a methodologicallack of subject matter understanding.
The development of a systemsapproach a new, whole world view, brought science out of a methodological crisis, while not discarding what has been achieved.
The generalcause of aging can be expressed only in the language of high-level abstraction as an objective pattern of life, being, as a principle, but not as specific mechanism in the organism. The reduction of principles to mechanisms is the main methodological error in the sciences, including in gerontology.
System analysis reflects not the material structure of the object that morphological sciences study, but a hierarchy of essential principles reflecting the laws of functioning and communication within and between the structural levels of the object being considered, which acts as a complex hierarchical dynamic system.
The commoncauseof aging is known as part of ontogenesis, part of life itself, as a phenomenon of disruptions in the structure and function of the system accumulating with age, as movements from order to chaos. In general, it is a natural process in nature, since it proceeds with an increasein entropy the accumulation of chaos in a systems.
Aging has been known since antiquity as a reduction in vitality with age. The current general definition of aging as a reduction in overall vitality with age.
The first mathematical model of aging was created almost 200 years ago by B. Gompertz (1825) and still most accurately describes the age dynamics of human mortality and, apparently, of most other organisms. Mortality, as quantitative characterization of the inability to resist destruction, can be viewed as the reciprocal of vitality.
A simple assumption about the stochasticity of the aging process is enough: the viability over time decreases in proportion to itself at each time point in order to obtain the basic law of aging: mortality increases with age by the exponent. Such a nonspecific increase in the bodys vulnerability to all influences with age is called aging itself:
d X / d t = k X,k is a coefficient, X is viability, t is time.
Considering the mortality (μ) as an inverse viability value (μ = 1 / X), the basic aging formula is obtained (B. Gompertz and W. Makekem):
μ = Ro exp (k t) + A,Ro is the initial mortality rate, k is the rate of increase in mortality, A is the coefficient characterizing the external influences to mortality.
The general mechanisms of such processes are clear these are principally probabilistic regularities associated with the ultimate stability of any elements delimited from the external environment; then a complex organism consisting of such elementary units can only lose them over time. The nature of such elementary units of life: non-renewing elements of the body (nerve cells, nephrons, alveoli, teeth, etc.).
Another approach to the quantitative assessment of aging, based on the same definition reducing overall viability with age, is to consider the overall viability of the system as an integral of the viability of its parts, which, as applied to the organism, means that the overall viability of the body consists of maintaining vitality (functional resource) of its main organs and systems:
Х = k1 х1 + k2 х2 +.+kn хn, where k is the coefficient, x1 n is the viability of organs and systems. The definition of individual aging as a biologicalage is based on this.
The common single cause of aging is manifested by the Main types (common mechanisms) of aging.
A fully formed organism has many non-updated elements at all its hierarchical levels: unique genes, non-dividing cells (for example, nerve cells, including autonomic control centers), non-regenerating structures of organs (alveoli, nephrons, etc.), organs themselves and etc. The loss of non-regenerating elements with age is probabilistic, and therefore in the simplest case, it is described by the same type of formula (Gompertz) as the loss of overall viability. It is the 1-st General Type of Aging. The only possibility at present to combat this aging mechanism: replacement of lost structuring units mechanical prostheses (e.g., dental care) and transplantation of organs and tissues. l
Age-accumulated of non-functional and toxic elements of different nature is 2-nd General Type of Aging. Activation of the organisms cleaning systems is a well-known and widely used tactic to influence this aging mechanism.
Aging of self-renewing elements of the organism structure (skin, mucous, parenchymal organs, etc.) is determined by a decrease in the rate of their self-renewal by reducing growth factors is the 3-d Main type of aging regulatory aging. Optimal is the impact on the regulatory centers and the introduction of tissue growth factors.
Global mechanisms of aging are manifested in the form of a variety of particular mechanisms for different structural units of the body, depending on the specific conditions and their structure. The effect on them is symptomatic. However, according to the common mechanisms, private mechanisms are grouped into aging syndromes, common to all effects (and diseases). Effects on them is the most promising at the moment, as you can use conventional remedies.
We have proposed a general model of growth an development and regulatory aging, which consists in disinhibition in the vegetative regulatory center (hypothalamus?) of stimulating cells when inhibiting cells die, which determines growth and development, but if death also affects stimulating regulatory cells, then over time the development program is depleted regulatory aging. This is essentially and very simple model that describes changes in viability (and mortality as a quantitative criterion of aging in general) during all periods of an organisms life.
Our formula is analogous to the formula of Gompertz-Makeham:
our formula: m=R*1/ (Ho*Exp (-k1*t) So*Exp (-k2*t) + c) + A;
Gompertz-Makeham formula: m = Ro * Exp (k*t) + A.
The most important formal differences are:
1. The exponent component, reflecting the age dependent mortality rate, is the result of the interaction of 2 exponents, reflecting stimulatory and inhibitory effects. This allows to simulate the initial shape of the mortality rate charts (125 years), characterized by a complex U-shaped.
2. The exponent component is influenced (mainly in its final segment) by the coefficient c, reflecting the presence of long-livers persons with a genetically reduced rate of aging. This allows to simulate the final shape of the mortality charts (80110 years), characterized by a complex S-shaped.
Our it is not empirical, and is based on fundamental biological processes and connects the aging process with the processes of growth and development. Regulatory non-dividing cells of the hypothalamus that produce growth factors in blood can be real morphological substratum (the h and s cells) of the described mechanism; for peripheral mechanisms a variety of growing and self-updating proliferating somatic cells, the growth of which is regulated by the level of growth-stimulating factors.
The systemic nature of aging also requires a systematic approach to the diagnosis of aging and its effects.
The book describes the feature requirements for the indicator of Biological age, the components of bioage and the computer system determining of bioage and related indicators, including automatic processing of bioage biomarkers using elements of artificial intelligence.
Another computer system described in the book makes it possible to study aging in detail by studying the dynamics of populationmortality using the formula of Gompertz-Makeham and its derivatives.
The use of mortality rate unless the external mortality component (m-A) graphs and the mortality rate increment (d (m)) graphs reflect the actual biological aging and show that the linear form of the graph (on a logarithmic scale) from the period of the end of growth and development remains the same, and decline in the rate of aging of centenarians.
The superposition of curves, reflecting the actual aging rate, shows that the aging is the same in history until 1950 for a number of countries, however, since the middle of the 20th century, the indicators of biological aging are constantly decreasing. Also increases maximum lifespan and reduces the coefficient k of Gompertz chart.
The effect of reducing the aging rate (d (m)) for middle ages is accompanied by the phenomenon of inversion of the overall mortality rate (m) for ages of long-livers: the natural m decrease, observed for all countries in earlier historical periods, is replaced by an increase in modern times. However, in the d (m) charts, it can be seen that the decrease in the aging rate of the long-livers is preserved throughout all historical periods. The latter means that the phenomenon of mortality inversion is associated with the external influences on mortality, and not with a change in the aging rate at this time.