Aging, the natural, complex and inevitable process in the life cycle of living beings, therefore also of man, according to today's knowledge, most likely takes place on the basis of a program located in the genome. This does not reduce the importance of dividing this process into normal or physiological aging and accelerated or pathological aging related to diseases. A whole set of current theories try to explain the essence of this process. In addition to different variations of the programmed aging theory, the following theories are also relevant: the theory of reactive oxygen species (ROS), cross-linking theory of long protein molecules, mutation theory, autoimmune theory, free radical Harman's theory, microglial aging theory, and the non-enzymatic glycation theory that is the result of the effects of advanced glycation end products (AGE compounds). According to the authors of this study, today's understanding of this inevitable, complex, one-way and irreversible event connected to living nature, with the crucial role of the five proteins mentioned in the title of this paper, is primarily based on the strong involvement of epigenetics in this complex process. Two basic processes related to epigenetics and essential for explaining the aging process, are deoxyribonucleic acids (DNA) methylation and DNA demethylation of CpG (cytosine/phosphate/guanine) sequences in the promoters of the LRP1 and RAGE genes. The first process, determined by deoxyribonucleic acid methyltransferases proteins (DNMTs), involves the insertion of methyl groups (-CH
3) at the C5 position of cytosine in the template strand of DNA, where these genes are located (formation of 5mC). The second process is the oxidative demethylation of 5mC via TET (ten-eleven translocates), TDG (thymine DNA glycosylase) and BER enzymes (base excision repair enzymes). The transcription processes of the five genes involved (LRP1, RAGE, DNMT1, DNMT3A, DNMT3B) have been taking place since the very beginning of life. In addition to their role in controlling growth and development, the crucial function of these processes is to repair the damage caused by a set of adverse events in complex macromolecular structures, mostly caused by the action of oxidation and glycation stress. In essence, this means the creation of new “healthy” receptors as mentioned. Here it is important to emphasize that genomic damage is otherwise subject to the effects of other reparation systems, but their analysis is not the subject of this study. The aforementioned “restorative” transcriptions, under the strong influence of transcription factors (TFs: Sp1, specificity protein 1; Sp3, specificity protein 3), take place under the control of their programs located in the genome. In order to maintain life in the harsh selection struggle typical for each species, there is a precisely determined maximum possible lifespan for its individuals. Here, the processes of DNA methylation and demethylation play an important role. They also have their own precisely defined programs, and the aim of this study is to try to provide answers to the question of the aforementioned interactions. An additional goal of this study is to present the latest findings on the specific blockade of, in old age, the increased expression of the RAGE receptor, and on targeted gene therapy aimed at the muted expression of the LRP1 receptor in old age.
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