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Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive cognitive decline. This review discusses current therapeutic strategies for the treatment of Alzheimer's disease, their limitations, and potential prospects. The feasibility of comprehensive approach for AD therapy is considered in contrast to the classical method in the development of therapeutic strategy. Leu-Ile, Glu-Trp, Lys-Glu, Gly-Pro, Glu-Asp-Arg, Lys-Glu-Asp, Met-Glu-His-Phe-Pro-Gly-Pro short peptides are described as multitarget agents with a wide range of activity.

The aim of this work is to verify the possibility of transport of 26 biologically active ultrashort peptides (USPs) into cells via LAT and PEPT family transporters. Molecular modeling and computer-assisted docking of peptide ligands revealed that the size and structure of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analysis of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters has been carried out. The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides, for which no biological activity has been established. This indicates an important possible role which LAT and PEPT family transporters may play in a variety of biological activities of the 26 biologically active peptides under investigation in this study. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp - or Glu - amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide are found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters. The data obtained lead to new prospects for further study of the mechanisms of transport of USP-based drugs into the cell and design of new antitumor drugs.

It was shown that KE peptide (Lys-Glu, vilon) has immunomodulatory, oncostatic and geroprotective effects. The aim of this work is to evaluate the effect of the KE peptide on gene expression and protein synthesis of SIRT1, PARP1, PARP2 during aging of human mesenchymal stem cells (MSC). The KE peptide increased gene expression and synthesis of the SIRT1 protein in «young» MSCs by 6 and 8,2 times, respectively. The KE peptide reduced gene expression and PARP1 protein synthesis during MSC aging by 2,1 and 5,3 times, respectively; and also reduced gene expression and PARP2 protein synthesis by 2,1 and 4,7 times, respectively. According to molecular modeling data, the KE peptide can interact with the GCGG sequence of double-stranded DNA (dsDNA) in the classical B-form and with the GGGC sequence of the curved dsDNA nucleosome. The indicated dsDNA sequences were found in the promoters of the human SIRT1, PARP1, PARP2 genes. Thus, the KE peptide regulates gene expression and synthesis of SIRT1, PARP1, PARP2 proteins in human mesenchymal stem cells during replicative ageing, which underlies the biological activity and geroprotective effect of this peptide.

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 differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides ® ), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific. We tested the capacity of the five peptides to influence cell cultures in vitro by incubating THP-1 cells with peptides at certain concentrations known for being effective on recipient cells in culture. We found that all five peptides can modulate key proliferative patterns, increasing tyrosine phosphorylation of mitogen-activated cytoplasmic kinases. In addition, the Chonluten tripeptide, derived from bronchial epithelial cells, inhibited in vitro tumor necrosis factor (TNF) production of monocytes exposed to pro-inflammatory bacterial lipopolysaccharide (LPS). The low TNF release by monocytes is linked to a documented mechanism of TNF tolerance, promoting attenuation of inflammatory action. Therefore, all peptides inhibited the expression of TNF and pro-inflammatory IL-6 cytokine stimulated by LPS on terminally differentiated THP-1 cells. Lastly, by incubating the THP1 cells, treated with the peptides, on a layer of activated endothelial cells (HUVECs activated by LPS), we observed a reduction in cell adhesion, a typical pro-inflammatory mechanism. Overall, the results suggest that the Khavinson Peptides ® cooperate as natural inducers of TNF tolerance in monocyte, and act on macrophages as anti-inflammatory molecules during inflammatory and microbial-mediated activity.

The review presents a literature analysis on the quality of medical care in general and the criteria for their assessment. The main discussion is conducted in several areas: what indicators are currently available; which of them can be used in elderly and senile age groups; what indicators should be used in this category of patients. Based on the review, it should be concluded, that the existing quality indicators do not reflect the specifics of providing care to elderly and senile people with chronic heart failure. It is concluded, that many issues have not yet been resolved and further research is needed on this issue. In our opinion, the assessment of the quality of medical care for chronic heart failure, primarily in elderly and senile patients, should be carried out taking into account age characteristics and using additional quality indicators, which should be introduced in a separate paragraph in the profile order.

Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA-peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.

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 influence of KED peptide on the expression of genes and synthesis of proteins regulating apoptosis, aging, neurogenesis, and involved in AD pathogenesis. Analysis of published reports and our experimental findings suggests that KED regulates the expression of genes of cell aging and apoptosis (р16, р21), genes (NES, GAP43) and proteins (nestin, GAP43) of the neuronal differentiation, and genes involved in AD pathogenesis (SUMO, APOE, and IGF1). The study the effectiveness of neuroprotective peptide KED in animal models of AD seems to be very important.

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, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms - in gray, hydrogen atoms - in white, and phosphorus atoms - in yellow.

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 the epigenetic regulators of gene expression and protein synthesis, which can be involve to the adaptation by stress and in the activation of hypothalamus-hypophysis-pineal and hypothalamus-hypophysis-thymus axises. These short peptides regulate the synthesis of proteins of heat shock, stress-protective proteins, cytocines, fibrinolysis and hemostasis factors and can participate in primary and tardive epigenetic regulation of adaptive response by stress, pathology and aging. The early functional diagnostic of element disturbances of organism unite humoral protective system by age-associative pathology can be usefull for the detection of deficient synchronization of epigenetic mechanisms, by wich the depletion and decrease of organism reserve possibilities occurs. The use of peptide can grade the adaptive syndrome manifestation by the stress and age pathology.

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. Based on the ranking of subjects according to the degree of decrease in body functions due to ageing and the development of age-associated diseases, an algorithm for the implementation of the assessment has been proposed. The possibility of using this algorithm has been substantiated, and its features have been shown on the example of St. Petersburg as a model region, taking into account its technical, personnel and organizational potential. The requirements for the implementation of the systemic support components for the provision of comprehensive medical, social and psychological assistance to senior citizens in the process of organizational and technical support for an integrated assessment of their biopsychosocial status have been defined.

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 activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117 + cells into mature CD28 + T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28 + , CD4 + , CD8 + T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28 + T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.

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 IL-1, NF-κB, and TGF-β and stimulates the synthesis of sirtuin-6. KE peptide normalizes the immunological function of human skin fibroblasts during their aging. AED peptide activates the synthesis of sirtuin-1, sirtuin-6, and collagen I in human skin fibroblasts during their replicative aging, which attests to its geroprotective effect.

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 known human proteome has not yet received sufficient attention. The incidence of bioregulatory peptide KE in proteins of various functional groups constituting human proteome is studied. The study is carried out with the use of the available data on the human proteome (UniProt portal) comprising 20,417 proteins. The levels of KE motifs were maximum in cytoplasmic and nuclear proteins, while the presence of KE in the membrane and all other proteins was the minimum. KE peptide molecules released from nuclear proteins during limited proteolysis can bind to DNA and regulate gene expression.

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 with due consideration of the dynamics of progression of age-associated chronic diseases of elderly people. The article describes the structure of the System, and the conditions and background of its establishment. It also looks at the components of system-based support of improvement of quality of life of elderly people. The article argues that it is essential to use the positive and negative experiences of different regions, to implement the practical and scientific expertise in the field of gerontology and geriatrics made so far in Russia, and to establish a meaningful and equal partnership among the state, research organizations, communities of professionals and non-public organizations. The authors suggest to look on Saint-Petersburg as a model region when establishing the System. The article contains a list of the major projects and events in the city from 2012 to 2020 aimed to provide system-based support for integrated health and social care for elderly people, not affiliated with any federal programs. Unbiased evaluation of the experience and expertise of Saint-Petersburg and other regions of Russia will allow to use them when establishing similar systems in other Russia's regions that do not possess sufficient resources. The authors suggest to establish the System in a step-wise manner at the federal district level. For example, a pilot project may be launched in the North-Western Federal District using the experience and expertise of Saint-Petersburg.

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 respiratory viruses. The pathogenesis of these infections is based on a wide range of innate immunity dysfunctions, manifested in the direct suppression of anti-inflammatory functions and, on the contrary, the activation of pro-inflammatory functions, such as the assembly and activation of NLRP3 inflammasome, as well as the synthesis and secretion of pro-inflammatory cytokines and chemokines. Excessive secretion of pro-inflammatory factors is accompanied by a disturbance in the balance of cytokines, leading to the development of a cytokine storm. When the body manages to cope with these disorders, a stable adaptive immunity develops, which is a harmonious combination of cellular and humoral mechanisms of resistance. Particularly difficult COVID-19 occurs in elderly and senile people. It has been shown that the main tests for the risk of multiple organ failure and death in COVID-19 in this category of patients are concomitant diseases, lymphocytopenia, increased transferases, D-dimer and other metabolic disorders. It has been established that critically ill COVID-19 patients develop endothelial dysfunction, thrombotic microangiopathy, immunothrombosis and disseminated intravascular coagulation, which are the basis of multiple organ failure. Pneumonia, as a complication of COVID-19, accompanied by the development of acute respiratory respiratory syndrome, ultimately leads to pulmonary fibrosis, which is often fatal. There is no specific therapy for COVID-19. Recently, immunomodulatory drugs have been widely introduced in the treatment of this infection, including remdesivir, synthetic quinine derivatives and neutralize antibodies.

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 properties of liver polypeptide complex (Ventvil) and KEDA tetrapeptide (Lys-Glu-Asp-Ala, Livagen). In liver pathology experimental models (liver fibroid induration, acute and chronic hepatitis) in amimals and in vitro was shown high efficiency of Ventvil and KEDA peptide. Ventvil and KEDA peptide had concordant effects - normalized immune and antioxidant status, restored liver function during hepatitis. It was demonstrated, that maximal hepato- and immunoprotective effect of peptides verified in aging.

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 neurodegenerative diseases, which are most often diagnosed at the stage of decompensation, when therapy is ineffective and does not bring positive outcomes. Most of the currently used drugs act only symptomatically. The review provides analyzed data and information about the prospects of using peptide bioregulators as neuroprotectors with high physiological activity and low immunogenicity.

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 used for normalized skin fibroblasts function: matrikines, carnosine, collagen peptides, cytokine and growth factor analogs, defensins, immunoprotective peptides and polyfunctional peptides. Polyfunctional peptides (AcSDKP, KED, AEDG, AED) have geroprotective properties, slow apoptosis and stimulate skin cell proliferation, also increase functional activity of skin fibroblasts, normalize intracellular matrix hemostasis. Polyfunctional peptides are the antioxidants and immunoprotectors and can activate microcirculation in dermis. Peptide regulation of skin function during ageing are the fast-developing and prospective area in molecular gerontology.

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 health and social care, its structure and the algorithm of delivering integrated health and social care to elderly people. The article argues that a system of integrated health and social care will improve the quality of life of older populations and extend their active longevity through a person-centered social services plan offered according to an older person's needs. The article gives the definition and a detailed description of the goals of system-based support of integrated health and social care for older populations. It describes the conditions for providing such system-based support in one specific region of the country. The article analyses the structure, aims and type of entity of the Geriatric Service which is viewed by the authors as a building block of the system of integrated health and social care for elderly people, and discusses the issues relating to coordination of activities among various divisions of the Geriatric Service and their cooperation with social services and healthcare providers. The article explains why it is important to establish a special research and methodological unit - the Center for System-Based Support - within the Geriatric Service.

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. The relative length of telomeric regions of metaphase chromosomes was evaluated by in situ fluorescence hybridization with DNA probes specific to telomeres. After incubation with peptide AEDG, significant changes in the relative telomere length were found in 7 of 11 individuals (3 cases in the younger age group and 4 cases in the middle age group). Significant increase in telomere length after exposure to peptide AEDG was revealed in 5 cases, including two individuals of the younger age group (by 41 and 55%) and three individuals of the middle age group (by 156, 18, and 76%). In one individual of the younger age group and in one of the middle-age group, a significant decrease in telomere length (by 37 and 15%, respectively) was found. A tendency to normalization of telomere lengths was noted: this parameter increased in individuals with initially lower telomere length relative to the group mean value and decreased in individuals with initially longer telomeres compared to the mean length in the group.

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 can affect the conformation of histone H1.3, which leads to a change in the chromatin structure in the loci of some genes, in particular Fkbp1b encoding the FK506-binding protein. Electrophysiological processes associated with the Ca^(2+) exchange are disturbed in the pyramidal neurons of the hippocampus during aging of the brain. The Fkbp1b gene encodes peptidyl-prolyl cis-trans isomerase, regulating the release of calcium ions from the sarcoplasmic and endoplasmic reticulum of neurons. The activation of the Fkbp1b gene transcription under treatment with short peptides can promote the synthesis of its protein product and the activation of the Ca^(2+) release from organelles of the sarcoplasmic and endoplasmic reticulum of neurons, which, in turn, can lead to an increase in the functional activity of neurons.

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 the polyfunctional cell population that synthesize a number of biologically active substances and participate in maintaining of extracellular matrix homeostasis, skin hydratation and endocrine and immune function. In the review genetic (accumulation of nuclear and mitochondrial DNA mistakes) and epigenetic factors of skin fibroblasts aging are described. Role of AP-1, NF-κB, c-jun, CCN1, TGF-β, TNF-α, MMP-1, MMP-3, MMP-8, MMP-9 and glycation in skin fibroblasts aging are discussed. There are some data about decreasing of skin fibroblasts ability to migration and synthesis of paxillins and aquaporin-3 (AQP3) during aging. Role of hormonal regulation in skin fibroblasts aging are described. Geroprotective action of melatonin to skin fibroblasts are showed. Reviewed molecular-cellular aspects of skin fibroblasts aging can be take into consideration for scientific background of using of cosmetic products for retarding of skin aging rate.

The article presents a modern understanding of the treatment of cardiac amyloidosis, provides data on the frequency of occurrence, classification and variants of clinical manifestations of transthyretin amyloidosis. This pathology is a slowly progressive disease, the symptoms of which usually appear in the elderly and senile age. This diagnosis may become more common in the future as the population ages and diagnostic methods improve. As an illustration, a description of the clinical case of transtritin amyloidosis of the heart in a 77-year-old patient, which occurred with a primary lesion of the heart and symptoms of chronic heart failure, is given. It shows the difficulties in the lifetime diagnosis of transthyretin amyloidosis.

The overview describes the clinical features of acute coronary syndrome in patients of older age groups. Atypical symptoms present in this cohort very often. It associated with a worse prognosis, partly due to delays in diagnosis, treatment, and insufficiently substantiated drug therapy. Comorbidity is one of the important factors complicating the diagnosis of elderly patients. Frailty, hyperglycemia, anemia, and chronic kidney disease are comorbid conditions, it identify in patients of older age groups often. High-sensitive cardiac markers is especially important for the differential diagnosis of acute coronary syndrome without ST elevation in elderly patients, because sometimes echocardiography does not provide additional information for interpreting the clinical case and there are no significant diagnostic changes on the ECG.

In review it is shown data about polypeptide vessel complex, extracted from calf vessel and named Slavinorm® (Vasolin). Slavinorm® had therapeutic effects in cardio-vascular age related pathology in animal models. Slavinorm® prevents atherosclerosis, normalizes lipid metabolism, lipid peroxidation parameters, station of congenital and adaptive immunity, callicrein-kinins system, vessel and trombocitary hemostasis, blood coagulability, fibrinolysis, activates vessel wall reparation. Slavinorm® has positive effects in other age-related diseases (arthritis, pancreatitis, respiratory distress).

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 «aging proteins» increased in 1,4-2,4 times. EG patients have abnormal microcirculation processes. It was shown as decreasing in 1,3 and 1,7 times of hemodynamic HI1 and H1-H3 indexes. EG patients have negative correlation of GDF15 concentration with arterial pressure. EG patients have no correlation of JAM-A/1 concentration with arterial pressure. Normal is positive correlation with GDF15, JAM-A/1 concentration with arterial pressure. GDF15 blood level during EG have positive correlation with HI1-HI3 and negative correlation with NEUR_HI2 and MAYER_HI3 indexes. It can show on pathogenesis mechanisms of endothelial and smooth muscles function of vessels tissues. We suppose, that the regulation of GDF11, GDF15, JAM-A/1, CCL11 «youth and aging proteins» can be target object of EG therapy.

More than a quarter of the elderly and senile age population suffers from kidney pathology. For this reason, a prophylaxis of kidney diseases with the safe and effective nephroprotectors is a priority of gerontology. An influence of polypeptide kidney complex (PKC), peptides AED, EDL, AEDG on the functional state of old rats kidneys was studied in research. Administration of PKC, peptides AED and EDL increased diuresis by 1,2-1,4 times. PKC and peptide AED reduced urine protein level and protein excretion by 1,5-2,8 times. PKC, peptides AED and EDL increased distal sodium transport by 1,2-1,3 times. Peptides AED and EDL increased sodium excretion by 1,3 and 1,6 times, respectively. Renal effects of peptide AEDG resulted in a reduction of glomerular filtration rate by 21%, decrease in urine protein level by 3,1 times and protein excretion - by 2,5 times. Peptide AEDG reduced absolute sodium reabsorption by 1,3 times and increased distal sodium transport by 1,4 times. Realization of glomerular-tubular and tubular-tubular balances is verified by correlation between glomerular filtration rate (GFR) and absolute sodium reabsorption, proximal and distal sodium reabsorption. In kidney tissue a stimulation of the antioxidant enzymes activity on the background of inhibition of the peroxidation processes intensity was observed, which in complex with morphological data evidences the absence of nephrotoxic effects. PKC, peptides AED, EDL and AEDG may be considered as nephroprotective agents in kidney aging.

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-protectors, and geroprotectors. Within the epiphysis polypeptide complex, free amino acids (3.26%), dipeptides (23.19%), tripeptides (50.72%), tetrapeptides (22.10%), and pentapeptides (0.72%) were revealed by mass spectrometry and HPLC. Peptide AEDG was detected among the tetrapeptides of the epiphysis polypeptide complex by selective reaction monitoring method. The biological effects of the epiphysis polypeptide complex are determined by the effect of its component AEDG.

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 found in the proteins of short-lived species - Norway rat Rattus norvegicus and house mouse Mus musculus.

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

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 hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer's disease.

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 antioxidant enzymes, suppression of LPO, and normalization of energy supply to kidneys cells. Our findings confirm the prospects of further studies of the nephroprotective properties of peptide EDL in various pathologies of the kidneys.

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 stimulate formation and growth of leaves in plant regenerants. Because the regulatory activity of the short peptides appears at low peptide concentrations, their action to some extent is like that of the activity of phytohormones, and it seems to have signaling character and epigenetic nature. The investigated peptides modulate in tobacco cells the expression of genes including genes responsible for tissue formation and cell differentiation. These peptides differently modulate expression of CLE family genes coding for known endogenous regulatory peptides, the KNOX1 genes (transcription factor genes) and GRF (growth regulatory factor) genes coding for respective DNA-binding proteins such as topoisomerases, nucleases, and others. Thus, at the level of transcription, plants have a system of short peptide regulation of formation of long-known peptide regulators of growth and development. The peptides studied here may be related to a new generation of plant growth regulators. They can be used in the experimental botany, plant molecular biology, biotechnology, and practical agronomy.

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 peptide bioregulator had increased the density of microvascular network of the pia mater in young animals ca. 1,2-fold and had not affected the perfusion and oxygen saturation of sensorimotor cortex. The second course treatment with «Slavinorm» was provided in a 6 months. Functional cumulation was revealed in 12 month-aged rats which had 2 course treatments with vascular peptide bioregulation: the density of microvascular network of the pia mater was increased ca. 1,6-fold; level of perfusion was increased ca. 15% in comparison with intact animals of the same age. These animals were more tolerant to cerebral vasospasm (the application of vasoconstrictor on the surface of the brain): the highest level of tissue oxygen saturation was remained at fairly constant perfusion in comparison with other animals.

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 untreated. Similar effect was obtained early for medical drug Epithalamin. Epithalamin also restored melatonin level in human and animals during aging. Thus, Pineamin and Epithalamin have similar stimulate effect on melatonin synthesis in elderly people pineal gland.

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 restricted budget and interagency separation was presented. Establishment of unified system of medical social support and gerotechnologies for the elderly was substantiated, as a mechanism facilitated life activity and decreasing of demographic loading on economic status of regions of Russian Federation. Legislative and normative regulations of gerontology and geriatric development were observed as well. Accepted legislative and normative acts were analyzed for period since 1977 to 2014. The necessity of approaches to regulation modernization for elderly was demonstrated. Analytical review on number of legislative state documents issued after meeting of Presidium of State Council of the Russian Federation being in August 2014 was also presented. Applicability of these documents for realization new strategy of gerontology and geriatrics development in Russia was proved.

The review is devoted to an actual problem of cosmetics in gerontology, one of molecular aspects of skin aging. Cell renewal processes slow down with aging, and the proliferation apoptosis ratio shifts towards cell death. One of the most pivotal apoptotic markers is the transcription factor p53. p53 protein expression in the skin keratinocytes increases under the influence of ultraviolet radiation. Wherein when exposed to ultraviolet radiation mutant forms of p53 have been revealed in 70 % of keratinocytes. On the one hand, suppression of p53 expression decreases apoptosis in skin cells that slows down the process of aging. On the other hand, it promotes the development of tumors in the skin. Thus, maintaining the physiological balance of p53 expression in skin cells is important for the basic and practical cosmetic medicine in gerontology. In addition, p53 protein may be used as a functionality marker of skin cells when administered with geroprotective cosmetic means and instrumental cosmetology methods.

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 blood oxygen saturation in the microvasculature of this tissue region raised.

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 and sirtuin-6 expression in «young» and «old» skin cell fibroblasts cultures was studied using immunofluorescence confocal microscopy method. The areas of expression of collagen type I and sirtuin-6 are known to decrease in skin fibroblasts with aging by 3,5 and 3,6 times accordingly. KE dipeptide increases collagen type I expression area in «old» skin fibroblasts cultures by 83%. KE dipeptide increases expression area of sirtuin-6 in «young» and «old» skin fibroblasts cultures by 1,6 and 2,6 times correspondingly. Thus, KE dipeptide promotes functional activity of skin fibroblasts and inhibits their aging.

The publication is the second part of the analytical review on the new stage of development of gerontology and geriatrics in Russia. Components of social support system for senior citizens and the structure of social-medical care as its crucial components are presented. The problem of positioning of geriatric care within the system of social support for senior citizens, as well as its peculiarities and the algorithm providing geriatric care are discussed. The analysis of this algorithm allowed us to justify the indissoluble link and continuity of individual components of geriatric care and its cost-effectiveness. The position of the Russian Federation Ministry of Health concerning of introduction of geriatric care as an element in the system of medical care for older citizens was looking through. The pilot project «Territory of Care» proposed by the Russian Federation Ministry of Labor and Ministry of Health for establishment of long-term system of medical and social care to citizens of the older generation on the principles of multidisciplinary and interdepartmental interaction was elucidated as well. Some failures of the project have been highlighted and recommendations for its development were stressed. The role of gerontology as a systemic basis for creation of geriatric service in Russia and for the development of an integrated social and medical care to citizens of the older generation was underlined. The main priorities in the field of aging in the forthcoming decade are formulated. The most promising areas of research in the field of gerontology were discussed, the implementation of which will allow to realize the State social policy goals focused on the quality of life of senior citizens. Finally, the position of Gerontological Society of the Russian Academy of Sciences on the creation of mechanisms of scientific support for the renovation of geriatric services, including collaboration with experts in the field of practical medicine, social workers, and organization of scientific coordination of all efforts for the development of geriatric care to citizens of the older generation are presented.

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 nuclear membrane and bind to DNA. Spatial models of DNA-peptide complexes are constructed for 19 short peptides by the docking method. Some peptides have the same binding sites. Peptides KE and EDP bind agat sequence, peptides KEDW and AED to acct sequence, and peptides AEDL and EDL to ctcc sequence.

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 malignant growth. A molecule JAM-C and JAM-C directly affect platelet’s adhesion to endothelial and dendritic cells, neutrophils, and other types of leukocytes, which makes their involvement in the regulation of hemostasis, and migration processes. JAM-A has an effect on the inflammatory response, leading to impaired cognitive function in HIV infection. JAM-B is involved in suppression of tumor growth in patients with Down syndrome. It is described the role of molecule JAM-A and JAM-C in the pathogenesis of hypertension, hypertensive crisis, atherosclerosis, cardiac abnormalities in the syndrome of Jacobson. Molecules JAM-B and JAM-C reduce the growth and invasion of human gliomas, and JAM-A has static effect against breast cancer. JAM-A molecule, JAM-B and JAM-C are involved in the development of inflammatory reactions and pathological neoangiogenesis in the cornea. The molecule JAM-C is involved in differentiation and polarization photoreceptors of the retina. The review provides own data of the authors, suggests the presence of epigenetic mechanisms of regulation of expression of the family of molecules JAMs, carried out with the direct participation of peptide geroprotectors.

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 rats (22-24 months) sensomotor cortex increased about 2,5-2,8 times compared to control old rates; and noradrenaline-induced constriction reactions and acetylcholine-induced dilative reactions of the pial arterioles increased significantly. This perfusion in the tissue of the cerebral cortex is not increased, but the degree of blood oxygen saturation in the microvasculature of this tissue region raised.

Telomerase is a ribonucleoprotein enzyme that elongates telomeres and therefore maintains chromosomal stability in germline, and 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 authors show that human tumor-derived ALT cell lines express a LINE-1 (L1) retrotransposon, which suggests its participation in telomere maintenance, possibly by a «slippage» mechanism of telomeric DNA synthesis. Moreover, suppression of the L1 encoded reverse transcriptase activity using an antisense strategy, or treatment of the ALT cells with the reverse transcriptase inhibitor 3'-azido-2',3'-dideoxythymidine (AZT), induces progressive telomere loss, arrest in G2-phase of the cell cycle, and, eventually, in cancer cell death. This finding suggests an exciting opportunity for the cure of up to 30 % of cancer cases.

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 activity. The goal of investigation was to study the KED peptide effect on signal molecules expression in normal, atherosclerotic and restenotic endothelium in vitro. It was shown, that KED peptide has normalized endothelin-1 expression, which increased during atherosclerosis and restenosis. KED peptide also restorates cells interactions by connexin expression. Geroprotective effect of KED peptide is realized by increasing of sirtuin1 expression, which has took part in DNA reparation.

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 concentration increases dramatically in schizophrenia, Alzheimer's disease, neuro-inflammatory disorders, cerebral malaria, drug addiction, as well as in atherosclerosis, periodontal disease, macular degeneration, cancer and other pathologies. In contrast to CCL11, differentiation growth factor 11 (GDF11), being administered to old mice, eliminates age-associated hypertrophy of the heart, improves muscle tone and prevents degenerative changes in the CNS, improves cognitive functions and enhances tissue regeneration. Its concentration decreases in cardiovascular disease, osteoporosis, and other «diseases of old age». At the same time, the higher the GDF11 level in the blood, the milder myocardial infarction, stroke and other age-related diseases of the cardiovascular system.

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 monkey females (Macaca mulatta). Five of them were injected with Pancragen (0,05 mg/animal per day during 10 days, intramuscularly) for 10 days; 4 animals received glimepiride (4 mg/animal per day during 10 days, per os). Blood samples were taken from all the animals with subsequent analysis of glucose, insulin and C peptide levels; the manipulation was performed before administration of the drugs, on the background of their administration and after their withdrawal in basal conditions, as well as during glucose tolerance testing. Pancragen and glimepiride administration induced the decrease of blood glucose basal levels in both groups of old monkeys. Pancragen also normalized insulin and C peptide levels suggesting its recovering effect on the disturbed tolerance to glucose in old animals. At the same time, glimepiride administration led to a more expressed and delayed hypoglycemic effect and C peptide secretion stimulation without any significant effect on insulin secretion. The data suggest that Pancragen is effective and safe for correction of age-related imbalance of endocrine pancreatic function, and can be used for elderly patient with disturbed glucose tolerance.