Pregledni rad
https://doi.org/10.21857/ygjwrc2d2y
One New Hypothesis about the Ageing Process of Man
Nikola Barić
; Private Family Medicine Practice, Labin, Croatia
*
* Dopisni autor.
Sažetak
Ageing, the natural, complex, purposeful, polysyllabic 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. Life is essentially a conglomeration of more or less complex physiological and biochemical processes that are constantly taking place, and whose alteration or shutdown leads to its termination. An accompanying and inevitable phenomenon related to a large part of these processes is the generation of the so-called reactive oxygen species (ROS), molecular structures that are characterized by two crucial properties, aggression and destruction of molecular body structures, and signaling effects, as secondary messengers, on the mentioned processes. Among these, the oxidative destruction of exposed molecular structures, according to some of the latest findings, have special importance for the process of programmed aging. Among these structures, two large transmembrane multiligand receptors, low-density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE), and three enzymes deoxyribonucleic acid cytosine methyltransferases (DNMTs), and two Sp1 and Sp3 transcription factors (Sp1 and Sp3 proteins) otherwise abundantly present in tissues and cells, are specially affected. ROS elements lead to a strong activation, transcription and expression of those two factors, Sp1 and Sp3, resulting in their strong effect on DNMTs promoters with pronounced transcription and formation of DNMTs proteins. What is the function of DNMTs proteins? As components of crucial importance in the systems of epigenetics, these proteins condition the methylation processes of DNA molecules (adding the methyl group -CH3 to the molecules), generate the formation of 5-methyl cytosine (5mC) on the template strands of DNA, and the decrease in the transcription of methylated genes while shutting down their expression. Due to the specific conditions related to LRP1 and RAGE receptors, their promoters have different reactions to DNMTs-induced methylation. In LRP1 pro
moter methylation is fast and intense, while in RAGE promoter methylation is extremely slowed down and reduced. Thus, the final effects of those two genes, or their receptors, are extremely different. Biochemical and physiological processes related to LRP1 gradually slow down and dampen, and processes related to RAGE become more and more expressive. Another group of processes related to epigenetics and programmed aging includes oxidative demethylation of 5mC DNA segments via ten-eleven translocases (TET), thymine DNA glycosylase (TDG) and base excision repair enzymes (BER). Everything indicates that this second group of events is less efficient than the first group, and methylation clearly dominates. If nature hadn’t programmed it that way, the aging process would be unpredictable. The increasing penetration of thought analyzes into the essence of the aging process, and the experimental results, increasingly point to the crucial importance of the process of transcription of the genes shown earlier. Regenerating transcriptions under the strong control of Sp proteins, and their programs located in the genome, influence the maximum possible life span of individuals of a species. The aim of this study is to provide additional explanations of the role of the mentioned receptors in the programmed aging of living beings. An additional goal of this study is the presentation of the latest findings on the specific blockade of, in old age, increased expression of the RAGE receptor, and on the targeted gene therapy, also in old age, of the muted expression of the LRP1 receptor.
Ključne riječi
Aging process; epigenetics; methylation and demethylation; LRP1 and RAGE receptors
Hrčak ID:
333440
URI
Datum izdavanja:
25.6.2025.
Posjeta: 682 *