In the process of human aging, an increase in the total amount of fat is observed mainly due to accumulation of lipids in non-adipose tissues. Insulin resistance, provoked by the intracellular accumulation of triglycerides, is often associated with development of such age-related diseases as atherosclerosis, type 2 diabetes, cancer, osteoporosis, and also with systemic inflammation and lipo- and glucose toxicity. Accumulation of lipids and lipophilic compounds is a biological phenomenon common for both prokaryotes and eukaryotes. Initially, it arose as an adaptation to starvation and shortage of nitrogen-containing nutrients, but later it converted into a depot of membrane material, needed on recommencement of cell division. In rodents and humans, the accumulation of non-metabolized fat in non-adipose tissues can be regarded as an adaptation to changes in the internal medium on a certain stage of ontogenesis as a result of age-related dysfunction of adipose tissue.
C1 compounds participate in various metabolic processes and regulations including DNA methylation. Formaldehyde (FA), a product of methyl group oxidation, is highly cytotoxic. In the cell, there are two pathways of its utilization: assimilation and oxidation. Formaldehyde displays cytotoxicity, and therefore its oxidation is considered as detoxification. The sensitivity to the threshold concentration of FA we regard as an indication of its major role in biosystem functioning. A model of a three-component conjugated redox system is proposed in which the methyl group oxidation pathway is an archaic and conservative donor of protons and electrons, the reduction of O2 serves as an acceptor, and the arginine amino group is used for production of both urea and nitric oxide (the donor and acceptor, respectively). The fourth component of the redox system is glutathione, which maintains redox balance. The three-level system of proton donors includes the oxidation of a methyl group (first level), the oxidation of acetate in mitochondria (second level), and glucose catabolism in the pentose phosphate pathway (third level). The whole redox system is united by the sulfhydryl groups of cysteines, glutathione, thioredoxin, and α-lipoic acid. The central regulatory role in this redox system belongs to glutathione-dependent formaldehyde dehydrogenase, which controls FA binding with tetrahydrofolic acid, arginine methylation, and denitrosation of sulfhydryl groups. The conjugated redox system was formed during evolution as a union of separate redox cycles of carbon, nitrogen, sulfur, and oxygen.
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