Unified theory of human and animals aging. Bioenergy concept aging as a disease - страница 8

1.3. Safety of free oxygen radicals generated by the mitochondria of a dying cell for neighboring cells. Due to the high chemical reactivity of free oxygen radicals and due to the small distances of their free path, neighboring cells with intact mitochondria are probably not susceptible to the pathogenic effects of these radicals.

First, in order to leave the mitochondria of a dying cell and get into a neighboring healthy cell, free radicals need to overcome many membranes with built-in densely packed proteins that contain a large number of potential targets for free radicals (unsaturated bonds in lipids and proteins; strong and numerous reducing agents in the form of natural antioxidants – vitamins, glutathione and thiol groups of proteins; as well as enzymes – catalase, peroxidase and superoxide dismutase, which neutralize radicals.

Secondly, even single free radicals that have reached the mitochondria of a neighboring healthy cell are able to engage in the normal functioning of their respiratory chains due to a chemical reaction with Coenzyme Q, a 50-fold excess of which in relation to other electron carriers (cytochromes, ferredoxins and dehydrogenases) is present in the inner membrane of mitochondria and diffuses freely in the membrane.

2. Activation of the disordered process of cell death – necrosis under conditions of deep or prolonged hypoxia, harmful to the surrounding tissues and to the organism as a whole. Disruption of apoptosis into necrosis is caused by a deficiency of oxygen and, consequently, a deficiency of free energy in the form of ATP and NAD(P)H, which are necessary to bring the energy-dependent process – apoptosis to the logical end.

3. Inflammation and autoimmune diseases. One of the last substrates inaccessible to proteases involved in apoptosis are transmembrane proteins of the plasma membrane. These proteins are present in apoptotic bodies, the end products of apoptosis, which are successfully captured by cells and digested by lysosomal enzymes of cells of the immune system. Interruption of this sequence of events under hypoxic conditions leads to the appearance of transmembrane proteins in the blood and to inflammation. The production of antibodies simultaneously against the external and intracellular epitopes of such proteins is likely to lead to autoimmune diseases accompanied by inflammation.

Some of these proteins may play the role of anchoring, that is, devices for mechanically fixing the contacts of a neuron and its extended processes with neighboring cells that have similar proteins in their membranes, the external water-soluble fragments of which form strong isological dimers with similar fragments of proteins of neighboring cells. After the death of a neuron and the triggering of a specific protease that cleaves off the outer fragments of these proteins, the latter form a densely packed and poorly metabolized conglomerate – beta-amyloid, which accumulates in the tissues of an aging organism.

The transmembrane precursor protein of beta amyloid could play the role of anchor fasteners only if its intracellular part was associated with the polymeric proteins of the cytoskeleton. A candidate for such a polymeric microtubule-forming protein is tubulin. Simultaneously with the appearance of extracellular deposits of amyloid beta during degeneration of neurons and their processes, intracellular deposition of aggregates of tau protein associated with microtubules is recorded. The simultaneous appearance of intracellular and extracellular protein aggregates during neuronal degeneration may be the result of the degradation of a single system that fixes extended nerve processes as they pass through tissues.