Unified theory of human and animals aging. Bioenergy concept aging as a disease. Алексей Фёдорович Фитин

peripheral part of the afferent system of innervation is a “servant of two states” – the sympathetic and parasympathetic divisions of the ANS, working alternately, and the “master” of the central division of the ANS, participating in the regulation of its work through the second nonspecific afferent system. Afferent connections of the ANS function around the clock, which leads to their primary depletion and degeneration.

      One of the most probable mechanisms for the depletion and death of afferent axons is the competition of two energy-consuming processes for a secondary energy source – a gradient of sodium cations on the plasma membrane. One of these processes is represented by the transmission of nerve impulses along an extended axon, and the other is the work of Na⁺-dependent glucose transport into a large volume of the cytoplasm. This is a system with mutual exhaustion, in which each of the processes slows down the other.

      2) The presence of unique pseudo-unipolar neurons, when the same neuron provides energy-consuming transport of nutrients and mitochondria over long distances in two different directions, connecting the innervated periphery with neurons of the brain stem or with neurons of the spinal cord.

      3) A large network of collaterals that communicate with the neurons of the second afferent system (additional energy costs).

      4) A dense network of extended afferent nerve fibers of the ANS, each of which departs from a small group of cells of internal organs or blood vessels (high energy consumption for the operation of the network).

      5) A decrease, for one reason or another, in the number of cells in such a small group, connected by electrotonic contacts and innervated by a separate axon, leads to an increasingly rare use of the nerve fiber and, as a result, to its degeneration.

      As for the efferent part of the arc of the unconditioned reflex, it is devoid of this “disadvantage”, since its functioning is based on a huge number of neurons and neural networks of the central division of the ANS.

      The efferent part of the arc of the unconditioned reflex of the sympathetic division of the ANS also has vulnerable links that contribute to its age-related degeneration.

      1) The ganglia of the sympathetic part of the ANS, in which the neurons of the efferent part of the arc of the unconditioned reflex are localized, are supplied with blood (oxygen and nutrients) on a common basis with other cells of the body. while the neurons of the afferent part of the arc, located in the nerve nodes of the spinal cord and the brain stem, are supplied with oxygen and nutrients in priority, like the neurons of the central nervous system.

      2) Degeneration of the afferent part of the arc of the unconditioned reflex, which provides negative feedback between the periphery and the central structures of the ANS located in the parts of the brain stem, leads to irreversible activation of the work of the efferent part of the arc. Long-term non-stop work of neurons of the efferent part of the arc leads to their depletion and death.

      However, even before the onset of depletion and subsequent death of neurons in the efferent part of the arc, such irreversible activation of neurons in the sympathetic part of the ANS leads to a number of pathological manifestations. Apparently, it is the long-term functioning of only the efferent part of the autonomic reflex arc, without feedback from the periphery that leads to hyperactivity of the sympathetic nervous system and to the initiation of the development of metabolic syndrome with an increased risk of developing type 2 diabetes, cardiovascular diseases and premature mortality [11].

      An obvious additional mechanism for accelerating the pathogenesis of aging at this stage is the wasted oxygen consumption for the excessive and generally not required by the periphery of the activity of the sympathetic nervous system in the absence of a reverse inhibitory afferent connection with the periphery (autocatalytic process). This is one example of the aggravation of hypoxia at one of the stages of the pathogenesis of aging. The second mechanism for the aggravation of hypoxia, initiated by impaired afferent connections, is due to the cessation of the supply of inhibitory signals to the brain stem structures through the neural networks of the second afferent system.

      Normally, the second afferent system transmits signals to the structures of the brain stem and, in particular, to the hypothalamus, inhibiting the activity of some of its nuclei. The cessation of this inhibitory activity due to the death of afferent endings, as a result, leads to a gradual release of inhibition and to the activation with age of some nuclei of the hypothalamus. A decrease with age in the intensity of inhibitory signals entering the hypothalamus through this system leads to activation of the endocrine system, designed to replace the regulatory function of the degenerated ANS.

      Replacement of the nervous regulation of the periphery with the endocrine one is also realized in additional non-productive oxygen consumption, that is, in an increase in hypoxia. Degeneration of the afferent nerve processes of the sympathetic division of the ANS through the second afferent system activates the production of corticotropin releasing hormone (CRH) by the hypothalamus, which stimulates the synthesis and export of adrenocorticotropic hormone (ACTH) by the pituitary gland, followed by an increase in the synthesis and export of cortisol by the adrenal glands.

      The mechanism of an increase in oxygen deficiency when switching metabolic regulation systems is due to the differences in the regulatory systems of metabolism – the autonomic nervous system (No. 1) and the endocrine system (No. 2). The autonomic nervous system activates metabolism quickly (promptly) and targeted, in those local volumes of organs and tissues, in which there is a need for additional amounts of oxygen and nutrients. Signals about this enter the central control structures of the ANS, located in the brain stem along the afferent nerve connections.

      As soon as there is a saturation with oxygen and nutrients of the considered local volume of an organ or tissue, negative feedback turns off the intensive supply of resources. Thus, targeted activation of metabolism for a short period of time means economical consumption of both oxygen and nutrients. A completely different situation with the consumption of oxygen and nutrients is realized in the case of the control of these processes by the endocrine system. At the request from the periphery (through the bloodstream, with a long delay) for an additional supply of oxygen and nutrients, there is a slow increase in the level of hormones in the blood.