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The effects of T-31, AB-17, and AB-9 peptides on old (passage 8) thymocyte culture were studied. Only AB-9 peptide exhibited a complex geroprotective effect on thymocytes during their aging. Peptide AB-9 stimulated proliferative activity and differentiation of thymocytes and inhibited their apoptosis. [ABSTRACT FROM AUTHOR]

The effect peptides KE, KED, AED and AEDG on proliferation (Ki-67), regeneration and aging (CD98hc), apoptosis (caspase-3), and extracellular matrix remodeling (MMP-9) in skin fibroblasts during their aging in culture were studied by immunofluorescent confocal microscopy. All studied peptides inhibited MMP-9 synthesis that increases during aging of skin fibroblasts and enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging. Peptides AED and AEDG suppressed caspase-dependent apoptosis that increases during aging of cell cultures.

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.

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.

A comparative study of polypeptides extracted from the tissues of calves: Cortexin (from brain cortex), Epinorm (from pineal gland), Ventvil (from liver), Prostatilen (from prostate), Thymalin (from thymus), Chelohart (from heart), Chondrolux (from cartilage) on the relevant organotypic tissue cultures of young and old rats, in concentration 0,01-100 ng/ml was performed. Polypeptides specifically stimulated "young" and "old" cell cultures growth in concentration 20-50 ng/ml. This effect correlates with increasing of PCNA and decreasing of p53 expression in brain cortex, pineal gland, liver, prostate, heart, cartilage. Moreover, Thymalin activated CD5, CD20 expression--markers of B-cells differentiation. These data show that polypeptides isolated from different tissues have selective molecular activity on the regeneration of suitable tissues in aging.

There are the point of molecular personified medicine view the applied importance of studying the expression of a variety of genetic and epigenetic factors (miRNAs, chemokines, cytokines, adhesion molecules, proliferation and apoptosis factors of vessel endothelium) as an innovative approach to the diagnostics and treatment of atherosclerosis, coronary heart disease, myocardial infarction. The review has described the data, which is connected with development new biological active vaso- and cardioprotective substances on the peptides base. These substances can regulate the expression of signaling molecules--the molecular markers of cardiovaslular diseases.

The review considers molecular mechanisms of chronic renal failure and cancer kidney disease. The most important molecules inducing inflammation are cytokines (MCP-1, TNFalpha, IFN-gamma, IL-1,6,8,18), matrix metalloproteinases MMP-2,3,9,14, tissue inhibitors of metalloproteinases (TIMPs) and grow factors (VEGF PDGE FGF). This signal molecules regulate the activity of immune cells and remodeling extracellular matrix (ECM) components taken place in inflammatory reactions, proliferation, apoptosis and also in the differentiation of kidney cells. On the basis of these data nowadays developed new highly selective approaches to diagnosis, prediction, estimation of efficiency of treatment of renal disease and creating of target drugs.

Peptide's bioregulators promotes restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of physiological activity of peptides is connected with its ability to regulate synthesis of protein markers of differentiation of neurons and retinal pigment epithelium epigenetically.

Cytokines CCL11 (eotaxin) and HMGB1 (alarmin1) are molecular markers of ageing and neurological, cardiovascular and immune diseases. Created in St. Petersburg Institute of Bioregulation and Gerontology short peptides are known to regulate gene expression and protein synthesis. They promote the mortality decrease and slowdown the development of pathology in the elderly. The article presents the proposed role of dipeptide vilon (Lys-Glu) and tetrapeptide epitalon (Ala-Glu-Asp-Gly) in CCL11 and HMGB1 genes regulation as activators of their expression. Geroprotective action of vilon and epitalon probably realizes in suppression of these genes.

Short peptides vesugen and D-7 have stimulated proliferation-associated protein Ki-67 decreased during aging in tissue-specific cell cultures received from young and old animals and in dissociated vascular endothelial cell cultures. Peptides vesugen and D-7 have interacted with promoter region of MKI67 gene coding protein Ki-67 that was obtained using methods of molecular docking. Both peptides have contacted with core promoter 5'-agcctcaaccatcaggaaaacaagagt-3' located in MKI67 gene from -14 to +12 base pairs relative to the transcriptional initiation site through sequence CATC(ENSG00000148773). Thus, vasoprotective effect of peptide vesugen revealed previously in elder people could be realized through epigenetic regulation of Ki-67 gene expression.

The influence of extreme radiofrequency millimeter microwave (EHF) and infrared (IR) electromagnetic emanation on the molecular markers of cell renovation (Ki67, p53) and proinflammatory cytokine TNF-α expression in the buccal cells of various age patients with chronic parodontitis was investigated. The results show that EHF- and IR-electromagnetic emanation increased Ki67 proliferative marker expression and decreased expression of proapoptosis protein p53 and proinflammatory cytokine TNF-α in the buccal epithelium of young, middle-aged and elderly people with chronic parodontitis. The data obtained open the new ability for patogenetic treatment of various age patients with chronic parodontitis using the EHF- and IR-electromagnetic emanation method.

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.