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Thermodynamics of aging


HomepageINSTITUTE of Physico-Chemical Problems of EvolutionBiological Evolution and AgingThermodynamics of aging

(Materials for the Symposium Thermodynamics and Information Theory in Biology 1998 AAAS Annual Meeting and Science Innovation Exposition AAASs 150-th Anniversary Celebration, 12-17 February Philadelphia, Pennsylvania, Monday, February 16, 3:00pm-6:00pm, Track: Emerging Science: Transforming the Next Generation)

SYNOPSYS

The findings of macrothermodynamics (supramolecular thermodynamics) of quasi-closed systems and the published data about the variation of the chemical composition of living organisms in ontogeny confirm the thermodynamic tendency of aging processes. According to the thermodynaic theory the specific value of the Gibbs function of the formation of supramolecular structures of the organism tends to a minimum. That tendency explains the variation of the supramolecular and chemical composition and the morphology of tissues during aging. The theory makes it possible to define the principles upon which proper diets and medications can be devised to slow down aging. Such diets and medications are also useful in preventative care and in the treatment of various pathologies and among them those attending old age. The principle of the stability of chemical substance of the supramolecular structures of tissues makes it possible to understand the causes of the practically unlimited evolution of the biological world from the perspective of the Second Law in its classical definition.

FOREWORD

This symposium is discussing issues of thermodynamics and information theory as applied to biology.

The first point that I would like to make is that from the point of view of the general laws of nature there is no direct link between classical thermodynamics, or just thermodynamics as we commonly refer to it, and information theory. Thermodynamic theory is a physical theory while information theory is entirely in the realm of mathematics.

The two disciplines do, however, use similar terms such as entropy, for instance. That term takes totally different meanings in thermodynamics and in information theory. Thermodynamic entropy and informational entropy have essentially nothing in common, or at any rate informational entropy bears no direct relation to the Second Law. "Neither is it related to orderliness, organization, or complexity".

Many researchers have tended to ignore this and as a result there ensued a measure of confusion in 20th century science, an unfortunate development, but an inevitable one.

Proceeding from the above I believe that a discussion of issues of thermodynamics and theory of information at this session is totally justified. Scientists must reach an understanding here. After all, both thermodynamics and information theory are powerful scientific tools that have emerged on the common ground of natural sciences including quantitative biology. Besides, the conclusions of evolutionary information theory should in principle relate to the principal thermodynamic tendency of evolution. There are no contradictions here. We need a variety of methods and models as part of our notion of the pursuit of science. An interdisciplinary discussion of thermodynamics and information theory may bring totally unexpected results and make for better understanding of the world around us, and more efficient use of the potential of the younger generation of scientists.

I have with me some references that may help clarify the problem, and in particular a paper by Dr. K.Denbigh, a classical natural scientist of this century.

THERMODYNAMIC THEORY OF AGING

Most of the known theories of aging deal with the aging mechanisms and emphasize the kinetics (dynamics) of the processes. There is extensive scientific and popular science resources dealing with the subject (Advances..., 1996; Klatz & Goldman, 1996; Pharmacological Intervention, 1996; The Science..., 1996; Yearbook..., 1997).

Another group of theories deals with the kinetic-thermodynamic aspects of aging. Most theories in that group rely upon models that deal with the changes in the production of entropy as part of aging (Lee III, Hershey, 1990). These theories derive from the work of I.Prigogine and coworkers. As a rule these theories essentially account for the rate of heat release of living organisms. In that case the heat effects describe the intensity of biochemical processes and indirectly relate to the structure of a biosystem.

Moreover, the change of entropy in an open system is related not only to the processes internal to the system but also to exchanges of matter and energy with the environment. As a result it is practically difficult to conduct any meaningful calculations and conclusions (Denbigh, 1989).

A number of available reviews relate to the Second Law and the origins and evolution of life. Some of them, however, contain a great deal of confusion. For instance, Cosmic Ancestry (http://www.panspermia.org/index.htm) in The Second Law of Thermodynamics contains quite a principled few mistakes. It would therefore appear to be extremely important to emphasize the need to use classical studies, especially where younger researchers are concerned.

I will confine myself merely to the thermodynamic - the thermostatic theory of aging. The theory relies on hierarchical thermodynamics or macrothermodynamics (structural thermodynamics) which investigates quasi-closed systems over limited time frames. The fundamentals of the theory are spelt out in my book Thermodynamic Theory of Evolution of Living Beings.

The theory that I will present has to labor under certain constraints as any physical theory. The approximate nature of that theory, as it appears now, derives above all from the difficulties in identifying the spontaneous tendencies of processes underway in open systems in comparing the thermodynamic stability of systems of variable composition. However, the same deficiencies are characteristic of the physical - chemical theories of solutions, other binary or multi-component systems comparing the thermodynamic functions of composite sets of variable constituency. At the same time the thermodynamic correlations that we have identified confirm that it makes sense quantitatively to compare the supramolecular stability of biological systems of differing compositions with a view to identifying the thermodynamic tendency of evolutionary processes (ontogeny, phylogeny). The impression is that the variations of the chemical composition of biological systems is accompanied by an averaging or smoothing of the standard reference levels of the thermodynamic functions. At any rate the nature of relationships of the type , where G - Gibbs function (Gibbs free energy), Tm - melting points of the substances, and others is a criterion for the extent of the approximation of our model (Gladyshev, 1996; 1997), (See: Appendix 1).

A few words now about important and known facts which any aging theory should be able to explain.

In our case it is necessary to understand the causes of the changes of the chemical composition of living organisms during the aging process from the perspective of quasi-closed systems and provide a quatitative justification of them (Gladyshev, 1978; 1997).. Figure 1 shows the changes in the amounts of water and fat in an evolving human embryo.


Fig.1. Variation of the amount of water and fat in a developing human embryo (Widdowson E.M., Body Composition in Animals and Man, 1967). 1 - water in fat-free tissue; 2 - water in tissue; 3 - fat in tissue. and -the amount of fat and water (weight %); M - mass of embryo.


These and other similar facts can be explained from the point of view of hierarchical thermodynamics bearing in mind the diagram presented in Figure 2. It shows that the motive force of ontogenesis is the tendency of the specific supramolecular component of the Gibbs function of biomass (biotissue), or to a minimum: . Here V is the volume of the system; m the mass of the selected microvolumes; x, y, and z are coordinates; the symbol "-" means that we consider the specific value of ; the symbol "~" stresses that the system is heterogeneous.


Fig.2. Schematic plot depicting the variation of the specific chemical energy capacity of the biomass - A (, or ) and the thermodynamic stability of its supramolecular structures during the ontogenesis of living beings - B (). The arrows near the axes (A) and (B) point the direction in which the energetic capacity and supramolecular stability increase. The growth of (>0) means that the energetic capacity of the system increases; displacement of to more negative values (<0) means that there is an increase of the supramolecular stability of the system.

The value A corresponds to the variation of - chemical component of the specific Gibbs function of chemical substance formation from chemical elements or simple substances (the chemical or molecular component). The value B corresponds to the variation of () - specific Gibbs function of the supramolecular structure formation in the course of self-assembly (the supramolecular component). The plots for A and B have different scales. The time axis is set by the Second Law of thermodynamics and has no scale. , - standard specific Gibbs function of the structure formation; is much larger than .

The specific values of and can be defined for unit volume or mass of the system. In both cases the dependencies shown in the figure are similar.

Usually in chemical thermodynamics the abscissas are given not by the values of time, t but the extent of the process accomplishment, .

The saw-tooth lines plotted against the curves emphasize that the fluctuation of the parameters of the surrounding, such as temperature, pressure, nature of food, nutrition schedule, physical fields, the change of day and night, the change of seasons, etc., lead to the variations of and . The organism adapts to these variations only within the limits of the adaptive zone.


The growth of the chemical component of the specific Gibbs function of biomass,or (or ), is secondary. According to supramolecular thermodynamics (the Second Law) the biosystem tends to accumulate energy-intensive chemicals that oust water from the system.

Figure 2 is in god agreement with the calculation we have conducted and given in Thermodynamics Theory of Evolution of Living Beings and other publications. This figure is in agreement too with data of J.Lepock, J.Engberts, F.Flandin and others.

The theory of hierarchical thermodynamics is quite reliable in my view because it is based on Gibbs thermodynamic theory. Separation of thermodynamic functions into components in keeping with the hierarchy of the structures of the real world makes good sense, because there are unidirectional series of life-spans (or relaxation times) of structures in different hierarchies. Figure 3 illustrates that regularity which evidently is a general law of nature.


Fig.3. Relation between the characteristic sizes (l) of structures belonging to different hierarchies and their life-spans (t) in the biomass.

The dependence is presented in the logarithmic scale. The scheme is based on the facts relating to Homo sapiens. For a separate community of several close species one can write: , where t is the average existence time (life-time) for "free" metabolite molecules, supramolecular structures, organells, cells of the biotissue, and also organisms, populations, community.


Let us go back now to the lower part of Figure 2 and consider the possibility of prolonging the life-span of an organism. Let us review a diagram given in Figure 4 (Gladyshev, 1995; Gladyshev, Komarov, 1996; Gladyshev, 1997).


Fig.4. Schematic variation of the specific Gibbs function corresponding to the formation of the aggregated phase of supramolecular structures for the biotissue of an organ of the j-th organism () in the course of ontogenesis.

The curve 1 describes the organism j living under given (standard) conditions of the habitat of (human) population. The dependence is determined by the genetic characteristics of the organism (genotype) j and by the given conditions of its habitat, i.e., the averaged parameters of the thermostat. The curves 1+ and 1- correspond to the individual j under the assumption that it lives under extremal conditions, which are different from the given ones. The area between the curves 1+ and 1- corresponds to the adaptive zone of variations due to the fluctuations of the habitat parameters. Within the limits of this zone, rejuvenation or accelerated aging is possible for the object (for instance, the biotissue or the whole organism).

The upper dashed line (Conception) relates to the conception of an individual (genotype) j, the value being predetermined genetically, corresponding to the habitat of the population.

The middle dashed line (Birth) relates to the birth of the animal (the man) j.

The lower dashed line (Death) corresponds to the death of the organism j; the death time can vary within the adaptive zone. It is determined by the changes in the habitat conditions.

The value is the variation of the specific Gibbs function for the biological object j during ontogenesis (as a result of aging) from conception to death. For example, for the aging of the collagen tissue of animals, . The variation characterizes the adaptive zone width at the moment t of the organisms life.

The values for concrete tissue can differ from the average values , which characterize an average individual living in average standard habitat (st). These differences can be described by the value , which can have different sign. It is a quantitative characteristics of the aging extent for the given object j at the moment of his life (t) or at the death moment. The shaded areas surrounding the dashed lines Conception, Birth, and Death denote the zones where the values , , and fluctuate.

The saw-tooth line plotted against the curve 1 symbolical emphasizes that the fluctuation of the parameters of the surrounding, such as temperature, pressure, nature of food, nutrition schedule, physical fields, the change of day and night, the change of seasons, etc., lead to the variation of . The organism adapts to these variations only within the limits of the adaptive zone.


In investigating the aging (ontogenesis) of the supramolecular structure of the biotissue, an organ or any other biosystem it is necessary to look at the effect of physical-chemical factors upon that process. Among those factors are temperature, pressure, calorie value and nature of food, the effects of synthetic chemical preparations and natural physiologically active compounds, physical loads, the effects of ionizing radiation, physical fields, etc. If the aging process takes place while these factors are constant and they can be viewed as parameters of the thermostat (habitat) the ontogenesis of the system draws to an end at a specific value of , which in a number of cases is close to its minimal value.

The average life expectancy (life-spans) of an organism is related to its genus and the averaged parameters of the environment. That is why for a given habitat for a particular genus the life expectancy of an organism is strictly preprogrammed. Any change in the habitat (or in the thermodynamic sense a transition to a new thermostat, for instance, as in cases of neoteny or a cancerous tumor) prompts the system to tend to a new value of , which can be greater or lesser than . If at some moment in the life cycle of an organism there occurred changes in its habitat so that < , it is quite probable that life expectancy will grow. The variation of the parameters of the environment (Figure 4) within certain limits (adaptive zone) contributes to either rejuvenation or aging of the organism. A transition for curve to curve thermodynamically amounts to rejuvenation, and transition from to , to aging.

Therefore the rejuvenation of a specific organism (organ, functional system or any local zone of bio-tissue) is possible (against a background of constant genetic characteristics of a given organism) only through the changes of the parameters of its habitat. The fluctuations of the parameters of the habitat (changes in the atmosphere, changes of the food, changes in the intensity of physical fields, etc.) cause changes of , which either rejuvenate or age the biotissues of the organism within the limits of the adaptive zone and manifest the thermodynamic force of the environment in the ontogenesis of the organism.

Here is an example.

If the diet of a species is changed in favor of unsaturated fatty acids the supramolecular structures (tissues) may became rejuvenated. The specific Gibbs function of the above structures () will tend to become a lesser negative value (transition from curve 1- to curve 1+ ). That thermodynamic effect correlates to the clinical practice of treating atherosclerosis with preparations like Linaetholum derived from linseed oil. The preparation contains a mix of ethyl ethers of oleic, linoleic and linolenic acids . The above fatty acids have a low melting point and display a positive value of at 250C (Figure 5). The ouster of high-melting fatty acids and fats by low-melting ones rejuvenate biotissues in agreement with the laws of thermodynamics. There are other similar instances of the rejuvenation of fatty, collagen and other biotissues. The facts established (Blandamer, Cullis, Engberts, 1996; Blokzijl, Engberts, 1993; Engberts, Hoekstra, 1995; Flandin, Buffevant, Herbage, 1984; Jones, 1979; Lepock, Frey, Senisterra, Heynen, 1995) positively indicate that the nascent gerontological thermodynamics will be instrumental in the development of new methodologies and the development of new preparations slowing down the process of aging.


Fig.5. The specific Gibbs function of non-equilibrium phase transition supercooled liquid solid as a function of (= - 298.2K) at 298K for a series of fatty acids; and are the specific Gibbs function of crystallization (condensation) and the melting temperature of the i-th compound, respectively. The value of is calculated per unit mass. The correlation does not vanish when is calculated per unit volume. Empty circles ()relate to the saturated fatty acids, filled circles () to the unsaturated fatty acid.

One of the applied aspects of the thermodynamic theory of the evolution of living organisms related to the problems of gerontology, nutrition, and some other medical and biological disciplines can be defined in the following manner (Gladyshev, 1997):

Diets incorporating "thermodynamically evolutionary juvenile" foods of vegetable and animal origins facilitate longevity and improve the quality of life. The extent of evolutionary juvenility of a natural foodstuff is determined by its chemical composition and supramolecular structure, which in turn depend on its phylogenetic and ontogenetic age, and also on the habitat of the organism - the source of the foodstuff. The value of the specific Gibbs function of the formation of the supramolecular structure is an important quantitative measure of the gerontological value of a natural foodstuff.

If a patients diet incorporates evolutionary undeveloped species of plants and animals (for instance, Algae - Spirulina Porphyra, Laminaria, etc. - Mollusca, Chondrichthyes, Amphibia, etc.) and uses the biomass of juvenile species he stands a chance to enrich his own biological tissues with juvenile chemical matter, a building material corresponding in its composition to a young organism. Another important consideration is the habitat of the organism whose biomass is used for the preparation of food. From that point of view foodstuffs that come from highlands or cold seas and cold areas have a high rejuvenating value.

This theory readily explains the facts of considerable extension for the life expectancy of animals fed lowcalorie foods or administered preparations that slow down digestion (Advances..., 1996; Sohal, Weindruch, 1996; Klatz & Goldman, 1996; The Science..., 1996). Physical chemistry is also the key to understanding the positive effect of seafood and food grown in highlands on human longevity.

Here is an example of the use of the principle in compiling diets that reduce the risk of cancer and facilitate the treatment of cancer.

From the point of view of chemical composition the evolution of a malignant tumor is accompanied by morbid rejuvenation: the tissues becomes enriched with water and the concentration of lipids and proteins falls dramatically.

This suggests that by increasing the concentration of lipids in the tumor, for example, one may slow down the process of its morbid rejuvenation and reduce the risk of emergence of cancer in preventative care.

It would see that this strategy of treatment and preventative care of cancer from the point of view of dietetics. The point is that the other strategy leading to a dramatic increase in the amount of water in the tissue (during fasting, for instance) should not be entirely successful despite the fact that in keeping with the principle of Le Chatelier-Brown the organism may respond by stimulating the synthesis of organic matter (lipids, proteins). The origination and growth of a malignant formation derive from a mutational transformation of genes. The organisms response in that case is practically impossible due to kinetic factors since the a directional spontaneous transformation of genes or their blocking may require a long time. Understandably, the more effective methods of treating cancer may be associated with intervention at the genetic level.

It follows from the above that anti-cancer diets should contain above all high concentrations of unsaturated fats, vegetable proteins in sufficient amounts and vitamins sustaining the organism and its protective systems. Diets of that kind should have a pointed anti-aging focus to be able to rule out negative effects especially where elderly patients are concerned. The above recommendation should also be followed in forming diets recommended for the prevention of cardiovascular diseases, Alzheimers disease and a number of others. A distinction should be drawn between preventative and curative diets.

Preventative diets can be recommended above all for people with a genetic predisposition for particular diseases.

Bearing in mind the above thermodynamic principle and published experimental data low-calorie rations should be used considering the following recommendations.

Diets aimed at reducing the risk of cancer

The use of sugar and large amounts of diary products is not recommended. Meat should be strictly limited. About 35-40 % of calorie content of the ration should be accounted for by unsaturated fats of vegetable oil and sea food (fish). The preferred options here are oils and fish fats with a low melting point. Oils extracted from plants that grow in cold climates should be preferred.

In that category are perillic, lallemantian, flax, sunflower, corn, mulberry, and buckthorn oils. The diet should also include fish, preferably cold water fish such as ice-fish (Channichthyidae), tuna, herring, cod, trout, salmon, etc.

Green vegetables and various beans should be incorporated into the diet in substantial concentrations.

In the case of genetic predisposition to cancer it is important to administer vitamins C, E, PP (niacin, nicotineamide) B, A (without counter-indications), zinc and selenium in doses ten times as high as normal (official recommended).

All other vitamins and minerals should be controlled within usual norms. The use of vitamins C and E in amounts exceeding norms tens of times cannot be ruled out here either. It has been demonstrated by L.Poling and other scienisists (Klatz & Goldman, 1996), that such doses are quite acceptable (Sci. America, 1996). It is also desirable to keep the concentration of iron in drinking water low (usual norm).

Diets recommended for treatment of cancer.

The recommendations follow those for preventative care and cancer risk reduction. However, the use of sugar and milk is totally ruled out and the doses of vitamins and minerals may be increased considerably.

Taking into account the experience of L.Poling and the most recent results of other studies (Eades, 1994; Pauling, 1986; Klatz & Goldman, 1996) one may recommend the following daily intakes of vitamins and minerals:

Vitamin - 10 g
Niacin (vitamin PP) - 2 g
B vitamin complex - 0,1 g
Vitamin - 800 I.U.
Vitamin - 30000 I.U.
Selenium - 500 mcg
Zinc - 40 g
Magnesium - 0,4 g

Other vitamins and minerals should be used in doses corresponding to official recommendations.

One of the possible mechanisms of the positive effect of fats during the treatment of cancer (from the perspective of supramolecular thermodynamics) is that cell membranes become enriched with lipid components, which leads to more intensive inter-cellular interactions. This in turn should impede the growth of metastases.

Many anti-cancer preparations are predominantly hydrophobic or contain groups with pronounced hydrophobic properties. This explains the positive effect of large doses of some vitamins in treating cancer observed by L.Poling (Eades, 1994; Pauling, 1986).

The latest findings of anti-aging medicine are in agreement with the general principles of the thermodynamics of aging and suggest the use of food additives such co-enzyme Q-10, blue-green algae, chlorella, melatonine, thyroid gland hormone, DHEA (dehydroepiandrosterone), deprenyl (eldepryl), aspirin, higher concentrations of chromium, etc (Klatz & Goldman, p. 317, 1997).

One must bear in mind that the use of extremely high concentrations of a number of vitamins and mineral additives untill now is questioned by a number of researchers and the U. S. Food and Drug Administration.

From the perspective of the thermodynamic theory of aging proposed by the author the idea is that companies produce food additives (vitamin complexes etc.) containing all physiologically important ingredients to make sure that their concentrations in the tissues of a patient be close to those of a young organism. Development of appropriate preparations would make it possible to rejuvenate not only individual tissues but the entire organism.

However, this would present considerable practical difficulties because in that case drug administration technologies ruling out or minimizing side effects will be required. For instance, the administration of hormones may lead to a hormones dependency. According to the Le Chatelier-Brown principle the synthesis of similar hormones in the organism will be suppressed.

Diets need to be corrected in the case of attendant pathologies (and in the case of particularity of patiens).

These recommendations have been made on the basis of the schematic in Figure 4 and numerous experimental data (Gladyshev, 1997; Goodnight, 1996; Lepock, Frey, Ritchie, 1993; Lepock, Frey, Senisterra, Heynen, 1995; Mazariegos at al., 1994; Nutrition, 1989; Widdowson, 1967) and also calculations based on the Gibbs-Helmholz equation: ,

where - specific enthalphy (variation of specific enthalpy) of melt - denaturation of the supramolecular structure (), - average melt point of i-th structure, - standard temperature. The results obtained are in good agreement with dietetic and clinical data (Advances, 1996; Klatz & Goldman, 1996; The Science, 1996; The Yearbook, 1997).

These recommendations clarify recognized principles and justifiably point to expediency of the use of foodstuffs based on plants and poikilothermal animals living in cold areas and also plants and animals of the cold seas. From that perspective, I would like to stress once again, cold sea and highland grown food are conducive to longevity. From the practical perspective of thermodynamics foodstuffs with low melt points of supramolecular structures should have pronounced rehabilitative effect. It must be understood that an optimal diet would be a great asset for the patient, but it cannot replace proper treatment based on medical indications.

It is also possible test the gerontological effect of medical preparations on the process of the aging of human biotissues. It is another method of evaluating the quality of medical preparations.

Many medical preparations (vitamins, trace elements, hormone emulators and other biologically active compounds) help sustain the physiologically optimal stability of the supramolecular structures of the biological tissues of the organism. That optimal stability (estimated by the value of the specific Gibbs function of the formation of the supramolecular structure) facilitates normal metabolism, slows down aging and improves the quality of life. Appropriate tests make it possible to identify the most effective preparations and recommend their doses from the point of view of gerontology. A geronotological screening of a preparation can rely on the known data about the chemical structure of the medicine, composition and the features of the supramolecular structures of biological tissues where the preparation needs to be localized (lipid structures, membranes, serum, collagen tissue, etc.) and on simple physical and chemical tests such as solubility in standard systems, etc.

Let us take a look now at some facts that have to the fore as a result of extensions of thermodynamic theory.

ON THE PRINCIPLE OF STABILITY OF SUPRAMOLECULAR STRUCTURES OF THE BIOMASS

Each structural hierarchy of the biological world represents a set of particles of the same type. In an hierarchy of small molecules the molecules themselves form that set, in a cellular hierarchy it is the cells, etc. Unitary particles are kinetically independent (in ideal solution or mixture) in each hierarchy and their concentrations determine the colligative properties of the system of a given hierarchy.

In some cases singling out the systems of independent hierarchies is fairly easy. This goes for instance for the simple homogenous ideal chemical systems such as solutions. However, if a complex heterogeneous system is split into hierarchies difficulties may arise. It is hard for example to size the supramolecular formations which act as kinetically independent fragments. For instance when an investigation is undertaken of nucleic acids in solutions it is assumed that a kinetically independent fragment consists on average of several dozen monomer nucleotide links. Evidently, for the practical perspective a kinetically independent fragment may be defined as a supramolecular formation that has melted in a narrow temperature range.

A living tissue is a supramolecular (im) hierarchical structure that has emerged as a result of phase transitions. Within that structure one may define several hierarchical sublevels (fragments, blocks). In investigating the evolution (aging) of such hierarchical substructures one can single out fairly small macrovolumes containing fragments of macromolecules and low molecular substances as kinetically independent formations taking part in phase balances.

Let us consider two cases.

1. If the above supramolecular structures of macrovolumes are not spatially isolated and are formed at relatively the same rates on the same time scale, their selection in the course of ontogenesis and phylogenesis is determined by the variation of the specific value of the total Gibbs function for their formation, . The value of is made up of many components corresponding to various types of interaction (Ch.Cantor and P.Schimmel, 1980; Tanford, 1994; G.Gladyshev, 1997). The value of , characterizing the extent of the completion of evolution (ontogenesis, phylogenesis) of the hierarchical sublevel, tends to a minimum. In that case , when some individual i-th components, may be greater than zero ().

2. If the times over which particles of hierarchical sublevels are formed are considerably different and the top sublevel stabilizes the bottom sublevel the structures of these sublevels may be viewed as independent hierarchical structures: j, (j-1) etc. In that situation the motive force of evolution is the variation of the Gibbs function of the formation of the top level j, i.e., , at < 0. However, the value of , characterizing the selection of some structures at the bottom level can be greater than zero. Here too as in the previous case (1), there is a direct analogy with the growth of against a background of overall decline of in a simplified model given in Figure 2. The above considerations are meant to clarify the model discussed (Figures 2 and 4).

The principle of the stability of chemical matter defined by the author (Gladyshev, 1997, Thermodynamic Theory of the Evolution of Living Beings, Appendix 2) is evidently applicable to the two above cases. The principle can defined as follows: during the formation of the comparatively more stable structures of the top hierarchical level (j) nature spontaneously prefers to use the comparatively less stable structures of lower hierarchical levels (j-1).

There are reliable experimental data confirming the applicability of the principle to the evolution of RNA. The selection of AU pairs (the less preferable choice from the point of view of the thermodynamics of the formation of secondary structure) in the evolutionary optimization of the structure of RNA (P.Schuster, 1993) is determined by the thermodynamic stability of higher supramolecular structures.

Similar results are given in the other works ( T.Mashkova et al., 1990) showing that the evolution of the secondary structure of 5S r- RNA of the higher plants is accompanied by growth of the component of the secondary structure which assumes a lesser negative value. Undoubtedly, during evolution there occurs the selection of the more stable ribonucleic complexes higher structures which form of the less stable structures of the secondary r-RNA structure. Therefore the selection of these fragments of the secondary structure is often the preferred option.

The two above facts related to the evolution of the RNA correspond to the principle of the stability of chemical substance. The impression is that this principle is applicable to various hierarchical levels of matter in the evolution of living systems. Perhaps it reflects an important feature of the evolution of living matter, that is the tendency of biological matter to evolve higher comparatively more stable structures as a result of the involvement of lower and comparatively less stable (energy-intensive) structures in the spontaneous processes of the formation of aggregate matter.

Another important consideration is that the principle of stability of chemical matter is a thermodynamic principle. It asserts that the tendency of the biosystem in evolution (ontogenesis and phylogenesis) to evolve highly stable structures of higher hierarchies leads to the selection of comparatively lesser stable structures of low hierarchies. That evolutionary tendency of the biosystems serves to rejuvenate the lower hierarchical structures and preserve an optimal stability of these structures and is the reason for the practically unlimited development of the biological world.

The thermodynamics of biosystems can be best investigated in terms of partial equilibriums. As has been noted it makes sense to single out within a supramolecular (im) hierarchy a series of spatial and/or temporal sub-hierarchies. The identification of temporal of sub-hierarchies is based on different relaxation times of the establishment of partial phase im-equilibrium in various sub-systems under study. The overall intermolecular equilibrium among comparatively large supramolecular structures (complex proteins, membrane fragments) is reached ( comparatively fast) only in minor local volumes. Partial im-equilibrium involving lower molecular components may become established fast in the volume of the entire organism. Such the partial im-equilibrium involving water molecules and other low molecular substances and ions. Electrochemical equilibrium may be reached practically instantly between biostructures located well away from each other in the organism.

I have no doubts that the fundamental notion of the proposed theory of aging are well justified. However, some details of the thermodynamic tendencies of aging need to be clarified. Additional experiments could serve to refine the theoretical model and stimulate the emergence of more evidence of the applicability of the Second Law in its classical definition to the investigation of the origins and evolution of life on Earth or elsewhere in the Universe.

I deliberately did not consider the problems of kinetics, i.e., mechanisms of aging in this report in order to avoid unwarranted polemics and attempt to understand the phenomenon of life from the perspective of general laws of nature.

Additional reference material about research in thermodynamics/thermostatics of aging and the limitations of the theoretical model is available at this page.


Appendix 1.

Schematic for the variation of Gibbs function of the formation of a supramolecular structure in a model binary system 2 ChS.

ChS chemical mater (except water) of the tissue ousting water from the bio-system during aging.

1 variation of assuming that the composition of ChS is constant.

2 actual variation of .

increment of caused by the variation of the composition of ChS during aging. Experimental data make it possible to assume that in a narrow range of 2/ChS concentration variation it is very often the case that << .


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