The indicator of the average life expectancy is associated with pathological or premature aging, and just like the indicator of the maximum life expectancy depends on the oxygen concentration in organs and tissues, but, at the same time, it is determined not by the rates of formation of carriers of free energy, but the rates of their expenditure.

Pathological aging is accelerated by the influence of numerous factors of a biological, chemical and physical nature, which is realized through a unified process of consumption of deficient oxygen or free energy, both on the work of the body’s safety systems (detoxification systems; immunity systems; stress response systems and supply systems a high level of selectivity of enzymes of matrix synthesis of DNA, RNA and protein, as well as a system for correcting errors made by these enzymes), as well as to overcome metabolic chaos in the form of diseases caused by infections, poisoning, distress and mutations, if the power of energy dependent security systems the body was not enough.

All expenditure of free energy by the body can be divided into two categories. The first is associated with the expenditure of free energy to maintain the basic vital functions, without which life is impossible, and which includes the costs of growth, development, reproduction, functioning, adaptation to small changes in the surrounding and internal environment of the body (costs for the constantly ongoing process of changing enzymatic patterns in cells and for the response to eustress), on maintaining body temperature and creating physiological endogenous reserves of nutrients for the smooth functioning of the body. The listed costs of energy are in a competitive relationship.

For example, the more free energy is spent on adaptation or on reproduction, the less it remains for other functions and the lower the indicator of the maximum life span of the species (see the example of the Shrew in the second part of the review). Another example – long-lived mutants of roundworms – soil nematodes Caenorhabditis elegans for the age-1 or daf-23 gene, encoding the catalytic subunit of phosphatidylinositol-3-kinase, localized in the signal transduction chain from the insulin-like growth factor, were characterized by either complete sterility, or fewer offspring and a high level of embryonic mortality.

I hope that the high energy consumption of the above basic vital functions is obvious to the reader, perhaps, except for the cost of adaptation. In this regard, I will briefly dwell on the mechanism of one of the most energy-consuming life processes – the adaptation of an organism to changes in its internal environment. The process of adaptation underlies the pathogenesis of aging as the longest chronic disease. This is not about the global (strategic) and slow process of adaptation of organisms to environmental conditions for many generations, which underlies the evolution of species and affects the changes in genes, but about the constantly going "every minute" adaptation of the organism to the continuous changes of the organism itself, manifested at the epigenetic level, without changing the genes themselves.

Such operational adaptation is expressed both in a change in the activity of enzymes due to a change in their content in cells, and in a change in their lists (patterns). It is impossible to constantly keep in the cells of this or that organ or tissue the entire set of necessary enzymes for all occasions. A large number of enzymes are classified as inducible and their amount in a cell can vary significantly depending on the situation. The relatively short half-life of many enzymes – from several tens of minutes to a day, indicates both the high rate of change of enzymatic “communities” (patterns) of the cell, and the significant expenditure of free energy, which goes both for synthesis and for degradation proteins. When I first drew attention to the high rate of protein turnover in the cell, I could not understand for a long time the reason for the high degree of cell wastefulness in terms of the expenditure of always deficient free energy.

Indeed, the ribosomal synthesis of only one peptide bond at a cost of 2 kcal/mol is accompanied by the consumption of four high-energy compounds (ATP, pyrophosphate and 2 GTP), with a total cost of 30 kcal/mol. In addition, the intracellular transport of protein to its workplace and folding of the protein into the working conformation also requires considerable additional energy consumption. The highest energy cost is characteristic of proteins delivered by energy-dependent vesicular transport over huge distances from the body of neurons along axons.

Only now, considering the energy costs underlying the life of cells and the organism as a whole, I realized the high cost of adaptation to the changing conditions of the internal environment of the organism. An example is the activation of the synthesis of a large list of enzymes under hypoxic conditions. For example, hypoxia of cell culture of cytotoxic T lymphocytes leads to an increase in the number of more than 7600 proteins [8]. Considering the huge variety of cells involved in the response to hypoxia, a large amount of the body's energy expenditures for adaptation to hypoxia should be assumed.

In my opinion, it is hypoxia that is the most common cause of changes in cell enzymatic patterns. A feature of hypoxia as a leading pathogenic factor is the high frequency of its manifestation in certain local volumes of organs and tissues. With age, the frequency of episodes of local hypoxia, their duration and depth increase, and, therefore, the expenditure of free energy both for adaptation and for exiting the adapted state and return to normoxia, also accompanied by a change in enzymatic patterns, increases.