Such an operation did not lead to any significant disturbances in the normal life of animals at rest and under constant environmental conditions. However, such animals lost the ability to quickly adapt and died from insignificant stressful influences. The behavior of the operated animals with a distant peripheral sympathetic nervous system reminded me of the behavior of elderly people. This similarity was expressed in a low threshold of a stress response to what seemed to be the most insignificant, both external and internal influences, manifested in humans in inadequately strong and unreasonable feelings, fears and worries.

This strengthened me in the consciousness that I was on the right track. I became interested in the fine structure of the ANS and the structural features of the neurons of this metabolic regulation system, looking for weak links that could make it the most vulnerable component of the aging mechanism of the body. The success of the search was largely predetermined by my “bioenergetic” past in science [6]. Since then, I have viewed all significant aging events through the prism of bioenergetics.

Such weak links were quickly discovered – incredibly extended processes of pseudo-unipolar neurons, in which a single axon leaves the cell body, splitting into two branches: a long one towards the sense organ and a short one towards the central nervous system, as well as slow and energy-consuming processes of axonal transport over long distances of tens of centimeters, which determines the slow process of their regeneration.

The volume of cytoplasm located in the extended processes of such neurons is hundreds of times greater than the volume of cytoplasm in the body of the neuron, in which the nucleus and the Golgi apparatus are localized, supplying the processes with all the necessary “building materials” for their growth and regeneration due to slow axonal vesicular transport, the speed which is much less than the blood flow velocity. The speed of vesicular transport in the axon reaches 20–50 cm / day, and the blood flow rate is in the range from 0.03 cm / sec in the capillaries to 40 cm / sec in the aorta.

Thus, the rate of vesicular axonal transport of mitochondria and enzymes accumulated in the Golgi apparatus and is 50–70000 times less than the rate of transport of nutrients by the circulatory system. This difference predetermines the limiting stage of the regeneration process of axons damaged in one way or another, which is from 2 to 5 mm per day. I came to the conclusion, that it is the energetics of these unique neurons that can be a limiting factor in their effective work and the regeneration of their offshoots. And since the energetics of a neuron is based on oxidative phosphorylation, I came to the preliminary conclusion that only oxygen can be the initial limiting factor in the work of these unique neurons. Later it turned out that the weakest point of these neurons are the terminal areas of axons farthest from the cell nucleus and from the Golgi apparatus, on which receptors are localized and which are capable of regeneration after physiological degeneration.

The death of the body is the inevitable outcome of the disease of aging. When assessing the dynamics of aging, two indicators are important – the average indicator and the indicator of the maximum life expectancy.

Searching for the stages of pathogenesis that limit a long and healthy life, I came to the conclusion that the indicator of the maximum or species life expectancy is associated with physiological aging (senescence) and depends on the only unique internal pathogenic factor – oxygen deficiency in organs and tissues and is determined by specific (per unit mass of body weight per unit of time) by the rate of formation of carriers of free energy [1] : adenosine triphosphoric acid (ATP), reduced forms of nicotinamide-adenine dinucleotides (NADH, NADPH), reduced forms of flavine-adenine dinucleotide (FAD) and acetyl-coenzyme A (acetyl-CoA).

Indicator of maximum life expectancy has not changed over the centuries and therefore is a species-specific feature. At the same time, the partial pressure of oxygen in different organs and tissues differs significantly, and therefore the levels of hypoxia, normoxia and hyperoxia for each organ and each tissue are unique [7].

Max Rubner first drew attention to the limitation of the maximum life span for the species of warm-blooded animals, while studying the energy characteristics of animals under resting conditions. More on this in the second part of the review.

Specific rates of synthesis of energy carriers, in turn, are determined not only by the partial pressure of oxygen in organs and tissues, but also by the specific content of mitochondria in cells, which catalyze the main process of synthesis of carriers of free energy – oxidative phosphorylation.

In a number of cells (stem, tumor) and tissues (embryonic tissue, fetus and «cambial» tissues of stem cell niches), in which aerobic glycolysis and the pentose phosphate cycle make a significant contribution to the production of free energy carriers, the amount of enzymes of these metabolic pathways present in cells also determines the specific rates of synthesis of free energy carriers.

Thus, the indicator of the maximum or species life expectancy of organisms is determined by the specific rates of synthesis of free energy carriers (per gram of tissues and organs per unit of time): ATP, NADH, NADPH, FMN, FADH2, Acetyl-CoA.

The parameter limiting the indicator of the maximum life span of a species, according to my proposed bioenergetic Concept of aging, is the specific rate (per kilogram of body weight) of the formation of carriers of free energy, which depends on the content in cells and activity of mitochondria that carry out oxidative phosphorylation of ADP and reduction of NAD+.