Vladimir Khavinson

St. Petersburg Institute of Bioregulation and Gerontology · Peptide department

Aim. Study of the effect of short di‐ and tetrapeptides (AB‐0, AE‐0) on the growth, development and productivity of Batya soybean varieties. Material and Methods. Biologically active dipeptide AB‐0 and tetrapeptide AE‐0 were used. Field studies were carried out on meadow‐brown podzolized gley heavy loamy soil. One month before planting, soybean see...

This study evaluates the effects of five different peptides, the Epitalon® tetrapeptide, the Vilon® dipeptide, the Thymogen® dipeptide, the Thymalin® peptide complex, and the Chonluten® tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differe...

Neuroprotective peptides are promising candidate molecules for the treatment of Alzheimer's disease (AD). Oral application of KED (Lys-Glu-Asp) improved memory and attention in elderly individuals with functional CNS disorders. Peptide KED also restores synaptic plasticity in in vitro model of AD. This review is focused on the analysis of the influ...

Results of comparative assessment of level of antibodies of IgG to SARS-CoV-2 in dynamics at standard and complex methods of treatment with use of medicinal peptide medicine of a timus of a timalin for patients with COVID-19 are presented in article. It was found that as a result of standard treatment, patients showed a decrease in antibody levels...

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that...

The organism adaptive possibilities by pathology and aging are discussed in account of the epigenetic. The organism adaptation to inner and external factors is carried out by organism unite humoral protective system, inclusive hypothalamus-hypophysis-pineal and hypothalamus-hypophysis-thymus axises. AEDG, AEDP, EDR, KED, EW, KE short peptides are t...

The article discusses the problems of determining the need of citizens of older age groups in complex medical, social and psychological assistance in the framework of the implementation of a personalized approach to the service provision. The concept of an integral assessment of the biopsychosocial status of older citizens has been introduced. Base...

We studied the effect of KE and AED peptides on the expression of sirtuin-1, sirtuin-6, collagen I, cytokines (IL-1, TGF-β), and transcription factor NF-κB in human skin fibroblasts during their replicative aging. Immunocytochemical analysis and confocal microscopy showed that KE peptide reduces the synthesis of factors of the inflammatory response...

Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activ...

Peptide KE exhibits immunoprotective, geroprotective, and oncostatic activities and stimulates functional activity of fibroblasts. The KE motif is present in amino acid sequences of some cytokines and peptide hormones functionally similar to KE peptide. However, the relationship between the presence of KE motif and protein functions on the scale of...

The current demographic situation in the world is characterized by an increase in average life expectancy, low birth rate, as well as an increase in the number of older and senior people, which is why our epoch is referred to as «the age of ageing». [...].

Short peptides are applied for supporting skin function during ageing, because they can permeate the intact stratum corneum of the epidermis and affect the cells of the dermis. Short peptides are part of natural metabolism of cells and many of them have geroprotective properties. In the review we are considering the base sorts of peptides that are...

The applying of many drugs in elderly and old people often is the reason of liver dysfunction. Thereat, the risk of liver fibroid induration, acute and chronic hepatitis increases during aging. It is the reason to find new, effective and harmless hepatoprotectors. In the review is shown the data of hepatoprotective, immunoprotective and antiageing...

Neurodegenerative diseases are a heterogeneous group of nervous system pathologies. They are found mainly in people of an older age group. The incidence of neurodegenerative diseases is continuously growing due to an increase in the average life expectancy of the population. At the moment, there are no effective and safe treatments for neurodegener...

The article examines the outlook and challenges relating to the provision of system-based support of healthcare providers and social services in the course of delivering their healthcare, mental health and social services to elderly people, in particular amidst a crisis, such as the COVID-19 pandemic. The article gives the definition of integrated...

The article examines the challenges of creating a system of integrated health and social care for elderly people (the System) in Russia, these challenges being of particular significance in the light of the negative effects of the COVID-19 pandemic on the quality of life and mental and general health of elderly people, which need to be mitigated wi...

The causative agents of coronavirus infection have long been considered the cause of benign respiratory diseases «common colds» until their pathogenic types appeared on the epidemic arena: SARS-CoV-1, MERS and finally, SARS-CoV-2. Diseases caused by the listed viruses characterized by moderate invasiveness and noticeable mortality compared to other...

The goal of the research is to study the effect of KE peptide on telomere length of PHA-stimulated blood lymphocytes of young and middle-aged men. 11 blood lymphocyte samples were enrolled in the analysis. Relative telomere length was measured using fluorescence in situ hybridization with DNA-probes specific to telomere sequences of human chromosom...

We studied the effect of peptide AEDG on telomere length and mitotic index of PHA-stimulated blood lymphocytes from young (18-22 years, N=5) and middle-aged (49-54 years, N=6) men. In the younger age group, no significant changes in the mitotic index were detected, while in the middle-aged group, a decrease in this parameter was found in one case....

Retinal diseases were always difficult problem for clinical ophthalmology. Modern methods of their treatment only decrease risk of complications, however in Russia was created better technology for this purpose: peptide bioregulators, which were made by sequential adding of amino acids one to another, binding with the promoter region of genes, and...

Cortexin is a clinically approved cerebral cortex polypeptide complex in calves. The mechanism of cortexin action is not understood well. Two cortexin derivatives, short peptides EDR and DS with neuroprotective activity, were synthesized. According to the data of molecular modeling, these peptides are able to bind to the histone H1.3 protein. This...

It has been demonstrated that short peptides play an important role in the transmission of biological information, modulation of transcription, and restoring genetically conditioned alterations occurring with age. Peptidergic regulation of homeostasis occupies an important place in physiological processes, which lead to the aging of cells, tissues,...

More than a quarter of the elderly and senile age population suffers from kidney pathology. For this reason, a prophylaxis of kidney diseases with safe and effective nephroprotectors is a priority of gerontology. This work studies the influence of the polypeptide kidney complex (PKC) and peptides AED, EDL, and AEDG, on the functional state of kidne...

Gerontocosmetology is the rapid developing knowledge area that has a very large applied meaning. Herewith a lot of information about skin aging and geroprotectors for skin rejuvenation hasn't a scientific background. Thus, understanding the fundamental mechanisms of skin aging becomes the actual task of molecular gerontology. Skin fibroblasts are t...

The data on the role of hypoxia-inducible factor, HIF-1, in the development of immunopathology (infectious, inflammatory, and autoimmune diseases), cancer (of the lung, brain, female reproductive system, urinary bladder, and pancreas), diabetes mellitus, and Alzheimer’s disease are analyzed. The data on the genes involving cell differentiation, apo...

The data on the molecular mechanisms of normal and pathological apoptosis are summarized. Three phases of apoptosis are distinguished: signal, effector, and degradation. The signal phase includes the extrinsic (caspase-dependent) and extrinsic (mitochondrial) pathways. Molecular markers of extrinsic and extrinsic apoptotic pathways play an importan...

Skin aging is an current problem of modern geriatric cosmetology. One promising method to decelerate the process of age-related skin changes is the use of cosmetics with short peptides. The goal of the work was to study the effect of peptide KE (Lys-Glu, Vilon) on the expression of aging markers of human fibroblasts in an in vitro model. The expres...

This publication is the second part of an analytical review of a new stage of development of gerontology and geriatrics in Russia. The components of a social-support system for senior citizens and the structure of social and medical support as its crucial components are presented. The problem of positioning the geriatric care within the system of s...

Essential hypertension (EG) is an age-associated disease. Often EG of elderly patients haven't good way of treatment. Thus, the search of new target molecules for EG therapy is an actual goal of gerontology and molecular medicine. It was shown, that during EG concentrations of GDF11 «youth protein» decreased in 3,3 times and GDF15, JAM-A/1, CCL11 «...

The polypeptide complex of the epiphysis and the peptide AEDG, constructed on the basis of its amino acid analysis, exert similar biological effects. Both bioregulators normalize melatonin synthesis in the pineal gland, functioning of the brain, eye retina, cardiovascular, endocrine, and immune systems; they also act as antioxidants, stress-protect...

On the page 553 Acknowledgements should be as follows: The study was supported by the Russian Science Foundation (grant 14-25-00024-P).

The effect of a pineal gland polypeptide complex, Pineamin, on urine excretion of 6-sulfatoxymelatonin (6-SOMT) was investigated by immunoenzyme assay in 55 elderly patients with decreased melatonin formation. Pineamin at a dose of 100 mg increased the level of 6-SOMT excretion in overnight urine by 1.9 times in comparison with the respective indic...

We have discovered motives of short-chain epigenetically active peptides in some proteins of long-lived African mole rat Heterocephalus glaber. These epigenetic regulators are located in the protein structure between lysine and arginine residues, thus facilitating their release in limited proteolysis. Some of these epigenetic regulators are not fou...

In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer’s disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippoca...

EDL peptide produced a nephroprotective effect on experimental models gentamycin-induced nephropathy and ischemia/reperfusion kidney injury in rats. The nephroprotective effect of EDL peptide manifested in prevention of oliguria and retention azotemia, a decrease in proteinuria and sodium excretion, prevention of critical decrease in activities of...

In recent years discussions have been held on the significance of pineal gland functioning changes in aging and age related pathologies. The purpose of study was to evaluate the latest results of long-term use of pineal gland peptides (PGP) in elderly patients with coronary artery disease (CAD). 79 patients with stable angina (2nd functional class)...

Exogenous short biologically active peptides epitalon (Ala-Glu-Asp-Gly), bronchogen (Ala-Glu-Asp-Leu), and vilon (Lys-Glu) at concentrations 10–7-10–9 M significantly influence growth, development, and differentiation of tobacco (Nicotiana tabacum) callus cultures. Epitalon and bronchogen, in particular, both increase growth of calluses and stimula...

The review is dedicated to one of the molecular factors of skin aging essential for cosmetic medicine for the elderly. Cell renewal processes slow down with aging, and the proliferation–apoptosis equilibrium shifts towards cell death. One of the pivotal apoptotic markers is transcription factor p53. Its expression in skin keratinocytes increases un...

In the cell culture experiments, the AEDL peptide proved to be an efficient agent stimulating the cell renewal processes and the enhancement of the functional activity of bronchial epithelial cells. A presumed target of the peptide action is a DNA molecule. The work studies the peptide binding with high-molecular DNA in solutions with different ion...

It was shown in different experimental models that short peptides possess anti-carcinogenic and geroprotective properties, while being safe in long-term administration to animals. Experimental studies of complex peptide bioregulators and synthetic peptides suggested major molecular mechanisms of their biological activity and identified specificity...

Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder. The study in functioning and aging of neurons may give an opportunity to regulate these processes. Previous investigations demonstrated the ability of EDR peptide (Glu-Asp-Arg) to penetrate a cell nucleus and stimulate gene expression. The data obtained prompt EDR peptide c...

We investigated the influence of vascular peptide bioregulator on microcirculation in the brain cortex of spontaneously hypertensive rats of different ages and figured out whether there is functional cumulation during two-time application of the drug «Slavinorm» by above-mentioned animals. It was shown that a single course treatment with vascular p...

Skin aging is one of the topical issues in modern gerontocosmetology. Application of cosmetic products with short peptides is a promising measure for retardation of skin aging. This research is aimed at investigation of KE (Lys-Glu, Vilon) dipeptide influence on the expression of markers of aging in human skin fibroblasts in vitro. Collagen type I...

This article is a 1st part of the analytical review, focused on a new step in development of geriatrics in Russia. Creation of state system geriatric care as important part of state politics in the area of enhancement of quality of life was proved. General aspects of improvement of social support of disable elderly persons in condition of restricte...

Using a TV device to study brain microcirculation, we found that after a course of vascular peptide bioregulator the density of microvascular network of pia matter of old hypertensive rats (12 months) sensomotor cortex increased about 1,7 times compared to intact old rates SHR. This perfusion in the tissue of the cerebral cortex and the degree of b...

It was investigated the influence of polypeptide complex Pineamin on the 6-sulfatoxymelatonin (aMT6S) excretion in urine by ELISA test of 55 elderly patients with diminished melatoninsynthesis pineal gland function. Pineamin in course dose 100 mg has increased night level of aMT6S urine excretion in 1,9 times in comparison with relevant value untre...

Short peptides constitute the system of signal molecules regulating the functions of the organism at the molecular, genetic, subcellular, cellular, and tissue levels. One short peptide can regulate dozens of genes, but the molecular mechanism of this process remains unclear. We suppose that short peptides penetrate through the cytoplasmic and nucle...

Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore maintains chromosomal stability in germ lines, as well as in the majority of cancer cells during cell doubling. However, up to 30% of human tumors of different types do not express telomerase but instead use an alternative lengthening of telomeres (ALT). Here we show th...

At a video facility for the study of intravital brain microcirculation, we found that, after a course treatment with vascular peptide bioregulator, the microvasculature density of the pial tunic in old (22–24 months) rats increased by about 2.5–2.8 times; the constriction and dilative reactions of the pial arterioles increased after the application...

The review covers the main functions of the family of adhesion molecules JAMs (Junctional adhesion molecules). This review provides information about the role of the molecules JAM-AH, JAM-BH and JAM-CF in the occurrence of pathological conditions, including diseases of the nervous and cardiovascular systems, atherosclerosis, thrombosis and malignan...

Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of mic...

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...

The article discusses the pool of signaling molecules that regulate the functional activity of the skin cells. Molecules of apoptosis and cells skin aging are p53, p21, p15, Cdk 4/6 and Bcl-2. Inflammation in skin fibroblasts are realized through the cytokines TNF-?, TGF-?, IL-1, ICAM-1, matrix metalloproteinase MMP-1,2,3,9, transcription factor NF...

Short (2–4 aa) peptides investigated increased life span of rats and improved various physiological functions and health status in aged people. Biological activities of peptides are tissue (cell) specific. Peptide bronchogen AlaGluAspLeu (AEDL) regulates synthesis of the Ki67, Mcl-1, p53, CD79, and NOS-3 proteins in cultures of the human bronchoepi...

GDF11 protein, the growth differentiation factor 11, which belongs to the TGF-β superfamily (transforming growth factor β), shows marked geroprotective effects on the cardiovascular and nervous systems. The cardioprotective and myoprotective effects of the GDF11 protein are associated with its regulation of several signaling molecules, including th...

Irisin produced by muscles during exercise and promoting fat burning also exhibits geroprotective effect and induces telomere elongation in normal somatic cells. Special attention is paid to studies of the role of peptides Lys-Glu, Glu-Asp-Arg, and Ala-Glu-Asp-Gly in epigenetic regulation of irisin content. The data suggest that the immunomodulator...

The paper presents the latest literature data on the structure and functions of «protein of juvenility» - CCL11 and «protein of senility» - GDF11. Chemokine CCL11 injected to young animals has been shown to lead to degenerative changes in the central nervous system (CNS), disturb cognitive functions and impede tissue regeneration. CCL11 concentrati...

Peptide KED (Lys-Glu-Asp) has vasoprotective effects and is effective substance in treatment of of atherosclerosis and other cardio-vascular disorders in elderly people. One of the probable mechanisms of biological activity of this peptide is epigenetic genes regulation. These genes can coding proteins, which are markers of endothelium functional a...

We studied the effect of melatonin and epithalon on age-related changes in proteolytic digestive enzyme activity in the pancreas and gastric mucosa of rats kept under different lighting conditions. In rats kept under standard illumination, pepsin activity and the total proteolytic activity in the stomach and pancreas increased by the age of 12 mont...

The effects of polypeptide complex from the kidney and short peptides AED, EDL, and AEDG on renal functions were studied in rats with cisplatin-induced acute renal failure. AED peptide decreased protein excretion and electrolyte concentration in the urine. Polypeptide complex from the kidney and peptides EDL and AEDG normalized diuresis, creatinine...

This review provides information about the structure and basic functions of the cytokine MIC-1/GDF15. MIC-1/GDF15 is normally contained not only in blood, but also expressed on cells of reproductive and nervous system. Its concentration increases in various diseases of the central nervous system, cardiovascular system, thromboembolism, malignant tu...

The search for new safe and efficient low-molecular weight substances stimulating skin regeneration is an important objective of geriatric cosmetology. The present study addressed the effects of the peptides LK and AEDG at concentrations of 0.05–2.00 ng/mL on the proliferation of organotypic tissue cultures of skin from young and old animals. The a...

The actual goal of gerontocosmetology is deal with the research of new effective and harmless low- molecular substances. The influence of LK and AEDG peptides in concentrations 0.05-2.00 ng/ml on organotypic skin cell cultures proliferation in young and old animals were investigated. Peptides stimulated skin fibroblasts proliferation on 29-45% in s...

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 c...

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 path...

Expression levels of genes encoding specific transcription factors and other functionally important proteins vary upon aging of pancreatic and bronchial epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect gene expression in pancreatic and bronchial cell cultures, respectively. It is established in this work that the DNA...

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, coro...

We performed a comparative analysis of biological activity of Lys-Glu peptide and its amino acid constituents. It was established that Lys-Glu stimulated proliferation of splenic cells in organotypic culture, while the mixture of glutamic acid and lysine inhibited culture growth. Using the method of molecular docking, we showed that glutamic acid,...

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 regu...

The aim of the investigation was comparative study of the influence tetrapeptide Pancragen (St. Petersburg Institute of Bioregulation and Gerontology, St. Petersburg) on hormonal function of the pancreas compared to the effect of widely used hypoglycemic drug - glimepiride. The investigation involved 9 old (20-25 years) clinically healthy rhesus mo...

The article represents evidence about structures, properties and functions of adhesion molecule JAM-A/1 belonging to JAM subfamily. This protein plays an important role in epithelial tight junction formation and immune function. Current article focuses on the role of JAM-A protein in pathogenesis associated to ageing: atherosclerosis, apoplexy, thr...

Brillouin light scattering studies of the behavior of hypersound velocity in solutions of short peptides Asp-Ser, Glu-Asp-Arg, Ala-Glu-Asp-Leu with widely varying concentrations at temperatures ranging from 295 to 360K are presented. As shown by analysis of experimental data and molecular simulation, the dipeptide Asp-Ser is characterized by format...

A marked increase elderly population in the structure of modern society is one of the main reasons for increase in the number of patients with type 2 diabetes and impaired glucose tolerance. The purpose of this research was to study impact of pancragen (tetrapeptide Lys-Glu-Asp-Trp) on endocrine function of the pancreas of non-human primates, femal...

We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the...

Factors significant for clinical-and-labor prognosis in elderly patients with ischemic heart disease after surgical myocardial revascularization are considered in the article. The authors demonstrate that for each level of the problem there are their own significant factors. Besides, the most essential correlations between investigated factors are...

During the peptides activity mechanism investigation it was shown that short peptides regulate gene expression and protein synthesis. These peptides stimulated cell proliferation, differentiation and decreased cell apoptosis. This effect is the reason of increasing of various organs function. The peptides injection decreased the frequency of cancer...

Peptide bioregulators promote restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of the physiological activity of peptides is associated with their ability to epigenetically regulate the synthesis of protein markers of the differentiation of retinal neurons a...

This paper reviews the results of long-term studies by the authors on the clinical efficacy of peptide bioregulators (Timalin, Thymogen, Vilon, Epithalamin, Prostatilen, Cortexin, and Retinalamin) for the prevention of diseases and treatment of people of all ages. Particular attention is paid to analysis of the use of peptide bioregulators as gerop...

Molecular mechanisms of the neuroprotective effect of peptide T-33 and cortexin were studied on organotypic cultures of the brain from young and old Wistar rats. The effective concentration of peptide T-33 stimulating proliferative activity of neurons considerably surpassed that of cortexin. Cortexin and peptide T-33 stimulated the expression of se...

Atherosclerosis is a leading cause of obliterating diseases of the arteries in 80-90% of cases. The main pathogenetic mechanism is endothelial dysfunction, leading to hypertension, diabetes, congestive heart failure. The desire of modern society to improve the quality of life increases interest of human health in general and sexual health in partic...

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 us...

Introduction: Some studies have shown that peptides have high treatment potential due to their biological activity, harmlessness, and tissue-specific action. Tetrapeptide Ala-Asp-Glu-Leu (ADEL) was effective on models of acute bacterial lung inflammation, fibrosis, and toxic lung damage in several studies. Methods: We measured Ki67, Mcl-1, p53,...