Unified theory of human and animals aging. Bioenergy concept aging as a disease - страница 9

4. Selective and reversible inhibition of the metabolism of a number of body cells under hypoxic conditions – mechanisms of oxygen saving (AMP-dependent protein kinase; ATP-dependent potassium channels; reversible inhibition of mitochondrial respiration by * NO radical, with the formation of nitrosylated hemes of cytochromes of the respiratory chain, not conducted by apoptosis). More on this in the second part of the review.

5. Cell poisoning due to a decrease in the activity of energy-dependent reactions for their detoxification and detoxification of the body as a whole: – a decrease in the activity of cytochrome P450 (NADPH-dependent), which carries out oxidative hydroxylation of xenobiotics – a reaction that stands at the beginning of numerous pathways of cell detoxification; – a decrease in the activity of the cell membrane glycoprotein Gp170 – ATP hydrolase, which energy-dependently removes organic pathogens of small molecular weight from the cell; – a decrease in the detoxification function of mitochondria, due to their death, due to the concentration in the mitochondria of a number of organs (liver), toxic metabolites and xenobiotics due to the energy of the difference in the electrochemical potential of the hydrogen ion on the inner mitochondrial membrane, followed by the fusion of mitochondria with lysosomes in the process of autophagy. Mitochondria, which occupy up to 30 % of the cell volume, are the most powerful detoxification systems that cleanse the cytoplasm from a large list of pathogenic factors of chemical and biological nature, thereby preventing chemical modification of various cytoplasmic enzymes by xenobiotics, thereby reducing the likelihood of metabolic chaos.

6. A decrease in the phosphate potential of cells under hypoxic conditions leads to qualitative and quantitative changes in the activity of hormonal systems of cascade regulation of metabolism, built on nucleotides and their derivatives (ATP, GTP, AMP, cyclo AMP, cyclo-GMP), as well as on regulatory enzymes: adenylate cyclases, guanylate cyclases and ATP-dependent protein kinases.

7. Qualitative changes in the systems of nervous regulation of metabolism: – decrease in the value of the potential of the cell membrane, leads to the problem of generation and propagation of the action potential; – a decrease in the ratio of guanine nucleotides (GTP / GDP) leads to significant problems in the synaptic transmission of a nerve impulse with the participation of G-proteins, which energetically remove a strongly bound neurotransmitter from the receptor due to the energy of GTP hydrolysis, thereby turning off the signal (solving the problem of the ratio selectivity and efficiency in the mechanism of synaptic signal transmission).

All of the above indicates hypoxia as a leading pathogenic factor in the disease of aging.

This section discusses the sequence of events connected by a network of cause-and-effect relationships and representing the pathogenesis of the disease of aging: – hypoxia; – decrease in the rate of formation of free energy carriers (ATP and NAD(P)H); – degeneration of sensitive nerve endings of the ANS; – irreversible activation of the efferent part of the arc of the unconditioned reflex; – depletion and degeneration of the efferent part of the arc of the unconditioned reflex; – switching the regulation of cellular metabolism and adaptation from the ANS to a less efficient and slow-acting endocrine system; – loss of differentiated properties by the cells of the denervated periphery and the acquisition of the properties of undifferentiated cells – the ability to proliferate and migrate.