General system theory of aging. Special role of the immune system

In the last 20—30 years, a great number of researchers worked in the field of gerontology – specialists from very different fields, including physicists, chemists, and others.

Studies by academician N.M. Emanuel marked the beginning of the development of antioxidants for the prevention of aging and bio-stimulation. A modern, extensive complex of creams and other skin care products practically does not do without substances of this group, as well as programs for the prevention of age-related diseases.

Modern anti-aging creams also include liposomes – the result of modern research on the theory and practice of artificial membranes, as well as hyaluronic acid and collagen – the result of traditional research on the aging of connective tissue of a large group of domestic and foreign scientists.

Modern studies on biorhythmology and methods of restoring and harmonizing biorhythms are undoubtedly related to the most ancient practices of acupuncture therapy in China. Modern electroacupuncture methods have proven their effectiveness (“longevity point”, etc.) and are waiting for wider use for the purposes of biostimulation and prolonging life.

Unfortunately, a large number of works claiming to discover the “fundamental causes and mechanisms” of aging, now have a purely historical interest. In many cases, these works only confused the essence of the issue, as they were based on particular issues, strengthening them to the general.

So, in fact, all theories that take the main role in aging chemical changes – the “spoilage” of proteins, DNA, colloids, etc. under the influence of cross-links, oxygen, etc., do not take into account the main feature of the living – self-renewal of the organism and cells and cannot explain the accumulation such changes over time.

Similarly, they did not give much either to practice or the theory of gerontologic and general conclusions not related to examining the organism in all its complexity: Rubner’s theory, which asserted that the amount of energy processed throughout one kilogram of body weight of different animals equally; theories about the “life hours” and the spending of the “life element” – the enzyme (I.I. Schmalhausen), the gene (L. Scillard), germplasm, differentiated cells and other material non-aging substrate; theories about the origin of aging in evolution as an adaptive mechanism (including the Weismann theory), ignoring the obvious fact of the overwhelming death of wild animals at a young age; general theories about the relationship of aging and development, reducing aging to a specific aging program, including the “death genes” or the programmed number of divisions for each cell (Hayflick’s theory), etc.; Carrel’s observations, pointing to the “immortality” of dividing cells and not taking into account the principle difference between population cellular phenomena and processes in the whole organism; Minot’s ideas, which associate cell differentiation with their death, but ignoring intracellular self-renewal, allowing non-fissile neurocytes to live throughout the whole organism and regulatetorus influences that sharply suppress potential-dividing cells, as well as many other ancient and modern theories. In general, it can be seen that research on the study of specific mechanisms of aging, very extensive and diverse, in most cases quite successfully led to the creation of various methods and means of biostimulation and prevention of individual manifestations of aging.

However, all the claims of researchers of this type to the creation of general theories of aging turned out to be completely untenable. This is not surprising since it is not methodologically correct to reduce the general laws and principles (namely, at this level, the analysis of the essence and cause of aging should be carried out) to separate mechanisms and manifestations – to particular aspects of the complex and diverse phenomenon of aging. The extreme specialization of modern scientists, which has led to just such a result, in recent years has finally been realized that it has stimulated the development of general methods of analysis – the theory of systems, self-organization, cybernetics, synergetics, etc. allow you to see the features of a common single natural theory of aging, to the creation of which all scientists aspired. The rapid development of statistics and demography somewhat overshadowed by the biology of aging, the achievements obtained by specialists in life expectancy biology. Thus, data from radiobiology, largely based on an analysis of the survival rate of irradiated animals, showed the possibility of accelerating natural aging – this is practically the only method that makes it possible to simulate accelerated aging adequate to the natural one. An analysis of historical mortality data allowed us to detect the phenomenon of the historical stability of the age-related component of mortality with a sharp decrease in the background or “external medium” component of mortality, which indicates the possibility of a sharp decrease in mortality due to socio-preventive measures, but denies the possibility of influencing in this way essentially, on the essential, internal processes of aging for the body (Dontsov, 2019).

Comparison of the age-related component of mortality for different regions of the World showed that although for each region they are historically stable, they differ for different regions.

It was mathematics that long ago resolved the dispute about the Maximum life span, as biologists believed, the “ultimate survival age” for organisms, replacing the absolute limit with the probabilistic survival law, as well as radically changing the notion of hereditary longevity, the ability to increase the Maximum life span with disease does not match the essence of aging, etc.

1.3. Methodology of knowledge: three stages, three paradigms

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 methodological lack of understanding of the subject matter. Although many gerontologists understood the importance of general biological laws (Bogomolets, 1938; Comfort, 1967; Dilman, 1981; Dogel, 1922; Frolkis V.V., Muradjan, 1992; Korshelt, 1925; Streler, 1964; Shmalgausen, 1926; Nagorny A.V., Nikitin V.N., Bulankin, 1963; Vojtenko, Poljuhov, 1986; Zavadsky, 1923), the main attention was drawn to the study of specific mechanisms of aging, issued as a reason. Science in historical development has gone through three stages, and each is characterized by its own general paradigm.

The first stage is determinism, which has received its maximum expression, apparently, in Laplace. According to his extreme ideas, know-ledge of the initial conditions uniquely determines everything that follows: knowledge of the initial coordinates and momentum of all particles at the Beginning of the World uniquely determines its picture to the present moment and the future of the World. The main disadvantage of this methodical approach is the mechanism: everything is predetermined by initial conditions, there is no freedom, in fact, there is no place for life, feeling, intelligence, free will and the whole diversity of the real World.

The subsequent development of science has changed this view of the opposite. The stochastic vision of the World, most pronounced in probability theory and quantum mechanics, was based on the recognition of a physical law stating that it is impossible to simultaneously and accurately determine the coordinate and momentum – the uncertainty principle in quantum physics. However, the proliferation of global stochasticity as a method from the micro level to the level of complex objects led to another extreme – the general unpredictability of phenomena, which also does not correspond to the state of things.

The development of a systems approach brought science out of a methodological crisis, while not discarding what has been achieved. Already one enumeration of its characteristic features, shown below, shows the enormous potential possibilities of a systematic approach – a new, whole world view (Checkland, 1986; Wolfram, 2002, etc.).

1.4. Features of the system approach as a modern universal scientific method of problem analysis

1.4.1. Using a systematic approach to analyze оf aging process

Already a short review of the system analysis requirements for the aging phenomenon makes it possible to see a number of crucially important points for analyzing the problem.

The principle of unity of the whole requires that a certain integral self-sufficient system be put in the basis of consideration. This means that the full consideration of aging is possible only for the level of the whole organism. Indeed, at the level of populations, the very concept of aging is blurred, as at the level of cells and molecules, when you can get a variety of cultural phenomena and interpret them in an arbitrary way. The importance of the principle of integrity, unity of the organism as a system is also clearly seen in the first experience of heart transplantation: in a couple of years the transplanted young heart was not much different from the old one: aging was directed by the whole organism, and the young part could not preserve its youth in the old organism. The same applies to the transfer of young stem cells to the old organism and vice versa: old cells retain their potencies and can manifest them in a young organism, while young cells reduce their abilities in the old organism (Albright., Makinodan,1976; Gorskaya et al., 2011) – the determining role of the microenvironment and external influences on the state of cells.

Considering the reality of universal interrelationships is all the more important since aging is a long-lasting process. At the same time, small changes and “side” for the main consideration of the reaction are decisive. So, besides the reactions directed by enzymes studied in biochemistry, all possible physicochemical processes in biological systems actually take place, which forms the basis of the aging processes in the form of “contamination” with secondary metabolites. Similarly, the universality of interrelations means a really huge number of influences on a real-life system and determines its fundamental vulnerability: the mortality of a particular system cannot be zero and even an “eternally young” organism will not be immortal – the stochastic mechanism of mortality. The same, when applied to specific internal structures, reveals the stochastic mechanism of system aging.

The idea that parts of a whole are not separate entities, but units of division of a fundamentally different type (entity-in-relationship) allows us to apply analysis methods at the abstract level and consider the real structure by considering the essential relationships of structural parts, which also applies to weakly structured systems (for example, metabolism for living organisms).

The most important position on the transition from the analysis of equilibrium states to the analysis of nonequilibrium, irreversible states (super) complex systems allows us to understand the fundamental unidirectionality of the aging phenomenon, to look for the presence of fundamentally irreducible phenomena that determine movement in one direction only.

The position of the system analysis that there is no entity, meaning and structure of an object outside of evolution, requires to consider the entire period of ontogenesis as a single whole, and not aging as a process that is separated from the development of the whole organism, needs to look for an association of aging with processes of growth and development of the body. In addition, the evolution of the living provides a vivid example of the evolution of the forms of aging and the possibilities of influencing it, as well as the dependence of such forms and influences on the specific structure of the living system of one or another level of complexity.

The principle of the consideration hierarchy actually reflects the different level of the real structure of the object, the presence of separate organs and systems with a special structure and function, which determines its particular mechanisms of aging for molecules, cells, organs, systems of the body and the whole organism with its common regulatory systems.

Finally, it is important to understand the essence of the phenomenon, which is considered as an ideal law that determines the appearance of the phenomenon, its functioning and evolution in the hierarchy of interrelationships of the whole.

This idea makes it possible to move away from considering the many specific mechanisms of aging to its cause, as an ideal principle and the essence of aging, and also to understand how the general principle is implemented by specific mechanisms. This is one of the stumbling blocks in modern gerontology, in which many open mechanisms of aging are given for a reason, which has already spawned hundreds of “theories” of aging.

The sticking point remains the question of the cause and nature of the phenomenon of aging, also solved by system analysis.

1.4.2. General methodology about the cause of phenomena

When one speaks of a single natural theory of aging, it is quite clear that it must answer a number of central questions:

– the time of appearance of aging in evolution;

– whether aging is a general law of nature or a private mechanism for the existence of individual forms of the living;

– what are the essence and the fundamental, common cause of aging;

– what are the general laws and particular types and mechanisms of the manifestation of aging;

– what are the fundamental features of human aging;

– what are the general perspectives and ways to overcome aging as a natural phenomenon;

– what are the specific approaches to the effects on the main types and mechanisms of aging;

– the importance of aging in general, the general way to overcome it, and the peculiarities of this task in humans.

One of the central issues in the consideration of aging as a global phenomenon is the question of the primary cause and the deep, fundamental nature of aging.

Regarding the general methodology for the consideration of the issue, it should be said that it was known in ancient times – Platon developed it in the most complete form. The leading contemporary philosopher-methodologist A.F. Losev formulates the most important provisions for us as follows: “Current experience gives us an idea only of flowing and scattered bodies and events, in which neither beginning nor end is seen and whose meaning remains vague due to its fluidity, very often incomprehensible and blind… And since the scientific understanding of a thing requires the final disclosure of its meaning, then the theory of ideas arises as ultimately developed communities.”. A full-fledged scientific analysis is characterized as follows: “To understand and correct components is necessary through the whole… The idea is the ultimate community, has a structure and is meaningfully filled, respectively has it’s own specific (own) … already purely ideal objectivity and reality… this limiting community manifests itself in its particular, in a semantic way, never moving beyond its limits… The essence (of something) is interpreted as a principle of structure…”.

Thus, it is clear that the essence, the cause 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 at all as a process, much less as a specific special mechanism in the body. The reduction of principles to mechanisms is the main methodological error in the natural sciences, including in gerontology. It is quite clear that when defining the term “aging”, the definition of the principle of aging as a phenomenon turns out to be necessary and sufficient, which has been known and understood for a long time: aging is a decrease in viability with age, or an increase in the probability of death with time, or, more, in general terms, it can be said that aging is an increase in the degree of chaos at all structural levels of the organism, which is manifested by a general decrease in the body’s resistance to all factors and is recorded as an increase in the probability of death from all causes of aging.

The definition reveals the very essence of the phenomenon of aging, which acts as a global, fundamental cause of aging because the cause of the accumulation of chaos (entropy) in closed systems has long been known: it is a law of nature, known in particular as the second law of thermo-dynamics. Now the interpretation of this law has significantly expanded and deepened in connection with its extension to information processes.

In biology and mathematics, the most interesting are modern trends: theories of self-organization, theories of open systems, describing the generation of information, its relationship with chaos, the role of energy in this process, etc.

The applicability of the second law of thermodynamics to living systems is related to the fact that they are only partially open systems: in any modern complex organism, there are structures that are not updated inside the organism – cells, molecules, organelles, organs, etc. Thus, the fundamental reason for the aging of any complex systems is the discreteness of the forms of existence of modern organisms on Earth – separation from the external environment, which puts a limit on the capacity for the internal evolution of an organism while preserving its quality as a separate system. In general, this is known as the inevitability of the accumulation of chaos in any partially open system limited from the external environment with time.

The self-renewability of a living system within itself is not a sufficient factor in counteracting aging in general, since it is possible to counteract the second law of thermodynamics only due to external influences on the system and these influences essentially lead to evolution, and not to stabilize any system.

1.4.3. Aging Hierarchy

The most important approach to the analysis in a systemic examination is to take into account the hierarchy of the structures of real complex systems. At the same time, system analysis requires consideration of principles characteristic of each hierarchical level.

Such a hierarchy of consideration in 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 following table gives an idea of the hierarchy of aging in terms of a systematic approach (Table 1).

Table 1. The hierarchy of consideration of aging in terms of a systematic approach

Three hierarchical levels of aging description are fundamentally ideal and are available only for theoretical analysis.

The last level is structural and its study is possible only when it is filled with biological content. With this consideration, it can be seen that the primary cause, as a principle, is manifested by several of the most common patterns – the types of aging inherent in all living systems. These types, in turn, form a number of interrelated groups of symptoms – aging syndromes, which already include specific manifestations of aging at the level of specific mechanisms that implement aging depending on specific conditions.

The systematic consideration of aging is also manifested in the fact that in each specific manifestation, the mechanism of aging, you can see all four levels mentioned above: a reflection of the ideal cause in specific conditions; relation to a greater extent to a certain type of aging; regular relationship at the level of mechanisms with other symptoms (syndromes); and, finally, the actual concrete actual manifestation of aging for the phenomenon under study in a specific case for a specific structure. Naturally, the more specific and narrow the phenomenon we study, the more specific, but more narrowly, the cause of aging manifests itself.

For the whole organism, aging as a whole can be sufficiently fully characterized only with the use of all four hierarchical levels of its presentation. An important and traditional is the structural consideration of the body or its individual elements.

Here again, the system approach allows revealing the moments obscured by usual consideration.

The dynamic view of the phenomenon under consideration indicates that living systems exist only as a stream, where continuity is preserved, but not always the entire real material structure. Processes in a living system occur at different time levels. So, at the metabolic level, these are (micro) seconds of biochemical reactions during which specific molecules exist; for cells, these are hours and days during which they are divided (cell cycle); for the whole organism, these are years, decades and even centuries.

Each level can have representation at a higher level with some of its structural elements (non-updated genes – at the cell level, non-dividing cells – at the suborgan level, etc.), then these lower-level elements become important for higher-level aging.

Each level is updated at the expense of a higher level, which reduces the absolute significance of the lowest level for aging higher (for example, cell growth and division sharply reduce the importance of aging or damage at the molecular level).

Each level is qualitatively different in structure and principles of organization and functioning.

All levels constitute a single whole, its change, in the final analysis, is only important as the aging of the organism is the aging of the whole.

Thus, consideration of the system analysis requirements for the aging phenomenon makes it possible to see the fundamentally important points of the problem analysis.

The most important is the ability to solve a number of central problems in gerontology in general, which allows to determine the common cause of aging systems and biological systems in particular, the main mechanisms for the manifestation of the common cause of aging, as well as the ways of manifestation of these common mechanisms of aging.

It is possible to identify the main properties of the biological system, which lead directly to its aging, to evaluate ways of influencing the aging of the organism and individual organs, systems, tissues and cells, as well as to clearly understand the prospects for such effects, their points of application and possible efficiency, as well as the fundamental The limited nature of these or other effects, the limits of their application and the ability to influence the aging of the whole organism.

The use of systems analysis puts gerontology as a science of aging on a clear methodological basis, leads it away from many circulating myths that are now replacing the general picture of aging and clear scientific views on it in gerontology.

System analysis in the first place allows you to move from the infinite consideration of particular views and mechanisms of aging to the consideration of the laws and principles that act during the aging of living systems, which just determines both the fundamentally possible main mechanisms of aging and the possible effects on it as well as the ultimate perspectives of such opportunities.

Thus, the use of the provisions of system analysis allows us to understand much in the problem of aging already at the level of abstract analysis.

1.5. Essential modeling – the basis of understanding the phenomenon of aging

The creation of theoretical models of the process under study is the most important element of knowledge, therefore this issue is given central attention in any modern field of science.

Gerontology in this regard is experiencing a crisis related to the fact that the old principles of creating conceptual models of aging, essentially reducing to the absolutization of certain observable phenomena and particular mechanisms of aging, have collapsed. All the so-called theories of aging, which now number hundreds already, have proved to be untenable in explaining the fundamental basis of aging and in many respects are only of historical interest.