[Prospects for use of short peptides in pharmacotherapeutic correction of Alzheimer's disease.]

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.

[KE peptide regulates SIRT1, PARP1, PARP2 gene expression and protein synthesis in human mesenchymal stem cells aging.]

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 «young¼ 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.

[Features of assessing the quality of medical care for patients with chronic heart failure of older age groups (review).]

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.

[Integral assessment of the biopsychosocial status of older citizens and implementation of the systemic support components.]

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.

Peptide KED: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease.

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.

[Epigenetic regulation of adaptogenesis by pathology and aging.]

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.

Results and Prospects of Using Activator of Hematopoietic Stem Cell Differentiation in Complex Therapy for Patients with COVID-19.

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.

Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells.

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.

Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging.

We studied the effect of KE and AED peptides on the expression of sirtuin-1, sirtuin-6, collagen I, cytokines (IL-1, TGF-ß), 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-ß 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.

[Neuroprotective effects of peptides.]

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: regulation of skin function during aging.]

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 influence of polypeptide liver complex and tetrapeptide KEDA on organism physiological function in norm and age-related pathology.]

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.

Peptide KE in Human Proteome.

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.

[Features of pathogenesis and COVID-19 course for the elderly and old age.]

The causative agents of coronavirus infection have long been considered the cause of benign respiratory diseases «common colds¼ 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.

[Regional System of Integrated Health and Social Care for Elderly People: Experience and Expertise of Saint-Petersburg.]

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.

[System-Based Support of Improvement of Quality of Life for Elderly People in Russia: Outlook and Challenges.]

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.

Effect of Peptide AEDG on Telomere Length and Mitotic Index of PHA-Stimulated Human Blood Lymphocytes.

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.

[Problems of diagnostics and treatment of transtiretinum amyloidosis with destruction of the heart in the elderly: Clinical experience.]

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.

[Polypeptide vessel complex and its role in physiology function regulation in aging pathology.]

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).

[Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b].

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.