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Thermodinamics of Aging

HomepageINSTITUTE of Physico-Chemical Problems of EvolutionBiological Evolution and AgingThermodinamics of Aging

Institute of Ecological Biophysical Chemistry

Ladies and Gentlemen, First of all I would like to thank the Organizing Committee for this opportunity to address the conference and take part in organizing this Session. My intent is first to dwell upon the general problems of thermodynamics in their classical definition, an area of research that is broadly used in science in general and in chemistry, biology and medicine in particular.

Many attempts have been undertaken in the second half of the 20 th century to bring together thermodynamics (thermostatics) and kinetics with a view of creating of general dynamic thermodynamics that would investigate non-equilibrium systems and processes, and especially processes taking place in the open systems. The thermodynamic theory of Clausius - Gibbs, as it seemed, could be easily applied only to the systems that are close to a state of equilibrium and to those that do not exchange matter with the environment (i.e., closed and isolated systems).

The fundamentals of hierarchical thermodynamics and macrothermodynamics have been defined over the past decade. The notions of quasi-closed systems were introduced and ways of using the variational principles of classical thermodynamics in investigating systems of that kind were identified. The notion of thermodynamic stability of heterogeneous systems, which can be assessed only by the integral Gibbs function of their formation is broadly used in hierarchical thermodynamics. Let us revisit the notion of system hierarchy.

Natural systems can be described as an assembly of co-subordinated subsystems, hierarchically related by size and spatial position (structural or spatial hierarchy) and (or) relaxation times of the processes in different structural hierarchies (temporal hierarchy). Besides that one can view the hierarchy of energies of the formation of structures of different types in aggregated matter, in particular in a complex heterogeneous system. For instance one can identify the chemical (molecular) component and the intermolecular (supramolecular) component of the energy of cohesion. In the basic case the Gibbs function (free energy) of the condensed living matter can be separated into the Gibbs function of the formation of molecules of that matter (hypothetical ideal gas) which may be designated as (or ), and the Gibbs function of the formation of supramolecular structure (or ) for the condensed state. In the case of heterogeneous systems such as microemulsions, suspensions, biological tissues, etc., if averaging can be done these quantities should be referenced to a unit of volume or mass and designated as the specific values and , respectively.

The values of and are integral and can be inferred from the expressions of the type: (1) and (2) where V - system volume; m - mass of released microvolumes; x, y and z - coordinates; the symbol " _ " indicates that and are specific values, and the symbol " ~ " underscores the heterogeneous nature of the system. The description of complex heterogeneous systems based on relationships (1) and (2) lend expediency to the notion of a macrothermodynamic description of such systems.

Let us now consider an open system located in a constant environment, for example, a chemical reactor (chromatographic column) into which a solution of substances is flowing spontaneously and within which these substances are adsorbed by a porous sorbent. Some of these substances can be adsorbed in the reactor. At the same time the substances that are not adsorbed stay in the solution and leave the reactor.

It can be easily shown that the amount of substances retained in the reactor is determined by their tendency to form stable thermodynamic supramolecular substance-sorbent structures. The more stable the supramolecular phase of substance is, the faster this particular substance is accumulated in the reactor. That is a consequence of the relationship:


where - retention time, A - coefficient, R - gas constant, T - temperature.

The stability of supramolecular structures retained in the reactor is determined by the value . On the whole the system (reactor) proves to be partially closed (quasi-closed) to the release of the adsorbed substances from the reactor. Such a system would be known as partially kinetically quasi-closed or quasi-closed. The above reactor inside which the chemical transformations occur and the matter is self-reproducing and self-assembling is a model of a living system. Let us dwell on the results obtained by methods of the thermodynamics of aging of living organisms.

Most of the known theories of aging deal with the aging mechanisms and emphasize the kinetics (dynamics) of the processes. There exist extensive scientific and popular science resources on this subject.

Another group of theories deals with the kinetic-thermodynamic aspects of aging. Most theories in that group rely upon models that study the changes in the production of entropy as a result of aging. These theories are derived from the work of I.Prigogine and co-workers. These works model the rate of heat release in living organisms. In that case the heat effects describe the intensity of biochemical processes and are indirectly related to the structure of biosystem. Moreover, the changes of entropy in an open system are related not only to heat effects of the processes internal to the system but also to exchanges with the environment. As a result it is practically impossible to conduct any meaningful calculations.

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

In our case it is necessary to understand the causes of the changes in the chemical composition of living organisms during the aging process from the perspective of quasi-closed systems and to provide a quantitative justification of them. 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 tissue; 2 - fat in tissue. m fat and m water - 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 connecting link between the two hierarchies: molecular and supramolecular. Figure 2 shows that the motive force behind ontogenesis is the tendency of the specific supramolecular component of the Gibbs function of biomass (biotissue or any biostructures, for example, the structures of telomeres) to a minimum.

The growth of the chemical component of biomass, that is its energy capacity ( or ) is secondary. According to supramolecular thermodynamics and the Second Law the biosystem tends to accumulate energy-intensive chemicals that oust water from the system. Figure 2 is in good agreement with the calculation we have conducted and with the experimental data.

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 ( ). >>

Separation of thermodynamic functions into components in keeping with the hierarchy of the structures of the real world makes good sense, because there are uni-directional series of lifespans, 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: ... << t m << t im << t organelle << t cell << t org << t pop << t soc << ... ,

where t is the average time of existence (life-time) for hierarchical structures - free metabolite molecules, supramolecular structures, organelles, cells of the biotissue, and also organisms, populations, communities. "The thermodynamics of j -th hierarchical level selects the structures of ( j- 1)-th level".

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 the diagram given in Figure . 4. A transition from curve 1 - to curve 1 + thermodynamically amounts to rejuvenation, and transition from 1 + to 1 - , to aging. Fig4. Schematic variation of the 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.

Therefore the rejuvenation of a specific organism (organ, functional system or any local zone of biotissue) 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 type, 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 ontogeny of the organism. One of the applied aspects of the thermodynamic theory of the evolution of living organisms related to the problems of gerontology, dietetics, nutrition and some other medical and biological disciplines can be defined in the following manner:

Diets, incorporating thermodynamically 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 patient's diet incorporates evolutionary undeveloped species of plants and animals and uses the biomass of juvenile species he or she has 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 have a high rejuvenating value.

Viewed from the perspective of the thermodynamic theory of aging commercial companies will be well-advised to produce food additives, vitamin complexes and drugs that contain all physiologically important ingredients of living tissues. The dosage of components should be such that their concentrations in the tissues of a patient were close to the concentrations of these substances in the tissues of a young organism . The introduction of such preparations would make it possible to rejuvenate not only individual tissues, but the entire organism.

Let us take a look now at some facts that have come to the fore as a result of the extension of macrothermodynamic theory.

The biological systems that I have been discussing are apparently governed by the principle of stabilization of chemical substance. The gist of that principle can be generally stated as follows: during the formation of the more stable structures of a higher hierarchical level (j) i.e., supramolecular structure, nature spontaneously predominantly uses the least stable structures of a lower hierarchical level, i.e., molecular (j-1).

The schema illustrates that principle.

Gases and Water - H 2 , N 2 , O 2 , CO 2 , H 2 O

T mol.decay 30001000 K High molecular stability
T melting 20273 K Low supramolecular stability

Tissues - Fats (Lipids), Proteins, Proteids, Sugars, RNA, DNA
T mol.decay 320 380 K Low molecular stability
T melting 273 383 K High supramolecular stability

For instance, the molecularly (chemically) stable substances such as H 2 , N 2 , O 2 , CO 2 , H 2 O have relatively low melting and boiling points that indicates the low thermodynamic stability of their condensed phases. On the other hand, such energy-intensive substances (with low molecular thermodynamic stability) as sugars, peptides, nucleic acids melt at relatively high temperatures and decompose during melting and boiling. The aggregated phases of these substances are highly stable!

The principle defined here is in agreement with the experimental data and calculations done for the Gibbs - Helmholtz equation: (4) where is an averaged measure of the stability of supramolecular structure, - specific enthalpy (variation of specific enthalpy) of melting - denaturation ( ) , T o - standard temperature, i.e., 25 0 , - melting point of i- th substance, and - variation of specific heat during melting. It is very important to bear in mind that the principle of the stability of chemical substance is a thermodynamic principle. According to it the tendency of biological system during evolution (ontogenesis and phylogenesis) to generate relatively highly stable structures of higher hierarchies lead to the selection of relatively less stable structures of lower hierarchies. That evolutionary tendency of the biological system rejuvenates the lower hierarchical structures and causes unbounded evolution of the biological world.

The theory that I have outlined offers an answer to questions about the origins of life in the Universe and the motive forces of evolution and aging. That answer is the thermodynamic force. One must not forget that natural selection at work at higher hierarchical levels is a manifestation of an important mechanism that assures the interaction of biological systems with the environment and helps their survival. But those problems first of all are in the realm of kinetics !

Additional experiments could refine the theoretical model and stimulate an effort to obtain additional proof that the Second Law can undoubtedly be applied in its classical definition to explain the origins of life on Earth or elsewhere in the Universe. Additional information about studies in macrothermodynamics can be obtained in some books and at INTERNET


We can formulate the conditions of equilibrium of a system as follows: in the equilibrium state of a system, its thermodynamics potentials have the minimum value upon constancy of their natural variables, while

the entropy has its maximum value upon constancy of the internal energy and volume of the system. These statements are correct only for the systems in which no work is being performed or only the work of expansion is performed.

S --> MAX (U and V are constants, Work = 0 or p dV)

The entropy of a simple system with fixed internal energy and volume tends to increase in natural (spontaneous) processes. When it reaches a maximum value, the system comes to equilibrium. The thermodynamic simple system is a system in which only the work of expansion is performed (or the work is not performed).


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 thermodynamic 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 specific for the old age. The principle of the stability of chemical substance of the supramolecular structures of tissues makes it possible to understand the causes of practically unlimited evolution of the biological world from the position of the Second Law in its classical definition.

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Institute of Physico-Chemical Problems of Evolution

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