[THE ROLE OF ENDOTHELIAL SIGNAL MOLECULES IN PATHOGENESIS OF AGE-ASSOCIATED DISEASES].

The article gives a summary of endothelial signal molecules that take part in homeostasis regulation and age-associated pathology development. Regulation of the endothelium function is realized by the system of signal molecules (NO, NOS, prostacyclin, thrombomodulin, tromboxan, antithrombin, endothelins, fibronectin, Willebrand's factor et al.). The change of their synthesis is the reason for the development of hypertonic disease, atherosclerosis, ischemic heart disease, myocardial infarction and other age-related pathology. The investigation of molecular mechanisms of endothelium functional activity is very important for creating new methods of diagnostics and treatment of cardio-vascular system age-associated pathology.

[INFLUENCE OF MILLIMETER-WAVE ELECTROMAGNETIC EMISSION ON NITRIC OXIDE SYNTHESIS DURING VESSEL ENDOTHELIUM AGING IN VITRO].

The applying of millimeter-wave electromagnetic emission (EHF-therapy) is an effective method for various age-related pathologies treatment, among other cardio-vascular diseases. During the EHF-emission of aging human endothelial cell cultures it was obtained changing of NO-synthase (eNOS), endothelin-1, angiotensin-2 and vasopressin expression dependence of irradiation exposition. These data have shown that EHF-emission has activated endothelium functional activity, which can play the important role to search for approaches to treatment of arterial hypertension and atherosclerosis.

[Tripeptides slow down aging process in renal cell culture].

The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.

[Ovary: ontogenesis and aging].

The neuroendocrine mechanisms of development and aging of ovary as the main reproductive organ are considered in the review. There are the analysed data of new investigation which is connected with the role of immune cells of ovary at involutive processes in reproductive system.

[Single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging].

The expression of matrix metalloproteinase 2 and 9 in thymus and pineal gland has been verified. These data demonstrate single mechanism of remodelling extracellular matrix in thymus and pineal gland at aging.

[Remodelling extracellular matrix in pineal gland at aging].

Matrix metalloproteinases (MMP) 2 and 9 has been verified in pineal gland, where MMP take part in remodelling extracellular matrix. Descrease of number MMP2 and 9 has been verified in pineal gland of old age and long liver people in comparison with middle age people. Pinealocytes and/or immune cells of pineal gland can synthesize matrix metalloproteinases.

[Changes of thymocyte differentiation, proliferation and apoptosis induced by syntetic peptides].

The changes in the processes of differentiation, proliferation and apoptosis were studied in the culture of human cortical thymocytes after cell exposure to T-32 and T-38 bioregulator peptides. T-32 and T-38 peptides were shown to enhance the differentiation of immature cortical thymocytes (CD4+CD8+) into T-regulatory cells by increasing their proliferate activity and decreasing the level of apoptosis. Moreover, these peptides were found to stimulate the proliferative and antiapoptotic activity of mature T-regulatory (CD4+CD25+) cells.

[The role of matrix metalloproteinases in human thymus aging].

The use of immunohistochemical method enabled to obtain for the first time expression ferments of extracellular matrix MMP2 and MMP9 in human thymus. Expression of matrix metalloproteinases is discreased in thymus of old age people in comparison with middle age people. These data testify to the important role of metalloproteinases 2 and 9 in extracellular interaction and proliferation activity in thymus aging.

[Characteristics of the pineal gland and thymus relationship in aging].

The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

[Neuroimmunoendocrine mechanisms of regulation of reproductive function].

Modern molecular biological studies have significantly improved understanding of structural and functional organization of the female reproductive system. The paper gives a brief overview of the literature and own research on verification and expression in the endometrium and placenta of many peptides, biogenic amines, steroids, cytokines and other signalling molecules, which, acting as hormones, enzymes, inhibitors, receptors, growth factors, immunoregulatory agents, transport's and binding proteins, provide the local regulation of intercellular neuroimmunoendocrine relationships that play a key role in the mechanisms of human embryogenesis and reproduction.

[Age-related features of immunocompetent cells of human placenta associated with diabetes mellitus].

The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B-lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B-lymphocytes in group of women with diabetes type I of younger age (18-28 years)--2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age.

[Peptidergic regulation of the expression of signal factors of fibroblast differentiation in the human prostate gland in cell aging].

The effect of short peptides T-32, T-38 and cardiogen on the expression of signaling factors of the differentiation of human prostate's fibroblasts (PFM), which are the main cells of its microenvironment--protein CXCL12, WEDC1 and ghrelin in aging cultures has been studied. Confocal laser microscopy has demonstrated that all the investigated peptides possess the ability to actively enhance the expression of the above markers, whose synthesis significantly reduced in senescent cultures. It has been shown that the rate of expression of the studied factors in older cultures (after 7 passages) under the action of the peptides have a tendency to even higher than those of controls (young culture, after 1 passage). Thus, peptide T-38 is the most active among the investigated ones. These studies show promise for detailed development of methods of peptides' regulation of aging and age-correction of violations of functioning of the prostate gland.

[Cell renovation in the intestinal epithelium in aging].

The ability to cell renovation of two basic cell types of intestinal mucosa is the important mechanism for the regulation and support of the gut physiological functions in aging and under the influence of the ecological negative factors. The study of the processes of cell renovation of the intestinal epithelial and neuroendocrine cells in physiological and radiological aging has a great interest, because the irradiation in the subletal doses could be considered as the model of artificial aging, and this fact enables studying of the radiological influence as the ecological factor, promoting the aging. In this study, the increase of cell proliferation in intestinal mucosa in physiological as well as artificial aging was observed. It was shown, that the total population of mitotic cells increases two times. These data testify about active participation of the mechanisms of cell renovation in the safety of gut functions during aging.

[Influence of peptides from pineal gland on thymus function at aging].

The interference between thymus and pineal gland during their involution is considered in this review. The research data about influence of thymus peptides on pineal gland and pineal peptides on thymus is summarized. Analysis of these data showed that pineal peptides (epithalamin, epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (thymalin, thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

[Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

[Neuroimmunoendocrine mechanisms of aging].

The review discusses in detail the mechanisms of aging from the position of common signaling molecules produced in three regulatory systems: the nervous, endocrine and immune ones. It is shown that the neuroimmunoendocrine hormonal regulation of homeostasis plays the important role in the complex chain of processes that lead to aging of cells, tissues, organs and body as a whole. Particular attention is paid to morpho-functional involution of nervous, endocrine and immune systems, which is accompanied by a breach of elaborate signaling molecules. Detailed analysis and further development of integrated molecular commonality of views on the regulatory systems of both the central and especially local levels, opens vast new opportunities for deepening knowledge of the mechanisms of aging, as well as for the prevention, diagnosis and treatment of diseases associated with aging, in which pathogenesis the discoordination of neuro-immuno-endocrine signaling mechanisms plays an important role.

[Expression of serotonin and vessel endothelial growth factor (VEGF) in human thymus in aging involution].

Immunohistochemical verification of serotonin and of the vessels endothelial growth factor (VEGF) has enabled to establish the presence of these signaling molecules in human thymus in all stages of ontogenesis and in aging. Thus authentic increase of quantity of the cells synthesizing serotonin in people of advanced age is established, which reflects the compensatory role of serotonin, directed on maintenance of immunity in old organism. The minimum quantity of the cells containing VEGF is observed in human thymus of advanced age, but the intensity of synthesis of this peptide does not practically change during the postnatal ontogenesis. These data may be considered as the evidence of the important role of signaling molecules that are expressed in thymus in local paracrine regulation of thymic functions in aging.

[A role of placental macrophages in gestosis pathogenesis in women of various age].

The main aim of this work was to determinate a role of placental macrophages in aetiology of gestosis and significance of pregnant women age during this pathology. We analyzed expression of CD68 (marker of placental macrophages) in placentas of healthy women and women with gestosis from younger and older age groups. We have found that in case of gestosis the increasing expression of placental macrophages at placentas of women younger than 30 years old takes place, although at placentas of women older than 30 years old expression of macrophages remains at stably high level during normal pregnancy flow and in case of gestosis.

[Serotonin and endotelin-1 expression in human thymus in aging].

The use of immunohistochemical method enabled to obtain for the first time the expression of two vasoactive hormones--serotonin and endothelin-1 in human thymus. The high level of the expression of these hormones has been shown in aging. Taking into account the immunoregulatory effects of serotonin and endothelin-1, and especially the activation of T-lymphocyte function under their influence, these data testify to the important role of these hormones in the regulation of immunity in aging.

[Expression of key regulatory apoptotic proteins and their role in thymic involution in human aging].

Immunohistochemical verification of the expression of pro-apoptotic protein p53 and anti-apoptotic protein mcl-1 in non-lymphoid structures of human thymus of different age groups has been carried out. It has been shown, that thymic involution starts very early in postnatal ontogenesis, which is testified by the decrease of mcl-1 expression during first months of child life, and at the same time the expression of pro-apoptotic protein p53 noticeably increases during the first year. It was established that deceleration of thymic involution is connected with the decrease of p53 expression, but not with the increase of mcl-1 expression during aging.