[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.

[Chondrocytes secretory phenotype associated with aging: role in the pathogenesis of osteoarthritis and prospects for peptide bioregulation.]

Osteoarthritis (OA) is a socially significant age-associated disease, for the treatment of which a search for new effective drugs is underway. The development of OA correlates with the development of the aging-associated secretory chondrocyte phenotype (SASP). The purpose of the review is to analyze the pool of signaling molecules that form SASP of chondrocytes in OA and substantiate the possibility of peptide chondroprotection. It has been established that SASP of chondrocytes is characterized by a decrease in the synthesis of sirtuins, impaired remodeling of the extracellular matrix, and activation of cytokine production. Sigumir, a polypeptide complex of cartilage and bone tissues of young animals, and the AED tripeptide (Kartalax) have shown high efficacy in animal models of OA and oral administration in patients with OA of older age groups. These peptide substances regulate the synthesis of proapoptotic and proliferotropic molecules that form the SASP of chondrocytes.

[The influence of peptides on the chondrogenic differentiation of human mesenchymal stem cells during replicative aging.]

Osteoarthritis is a widespread age-related disease, that has no effective targeted therapy. In this regard, bioengineering methods are being actively developed that can stimulate the restoration of cartilage tissue. These methods include chondrogenic differentiation of stem cells, which is stimulated by various biomolecules, including short peptides and polypeptide complexes. It was studied the effect of the cartilage polypeptide complex (CPC) and AED peptide on gene expression and protein synthesis of chondrogenic differentiation - SOX9, aggrecan, type II collagen and COMP - in human mesenchymal stem cell (MSC) during replicative aging. AED peptide at the concentration of 200 ng/ml activates gene expression and protein synthesis during aging of MSCs. CPC has the same effect in the concentration 2000 ng/ml. These data indicate the stimulating effect of studied peptides on regulation of chondrogenesis and open up prospects for further investigation of their effectiveness in osteoarthritis models.

[Peptides prevent the forming of secretory phenotype of chondrocytes associated with the aging.]

Secretory phenotype associated with the aging (SASP) of chondrocytes forms the conditions for the musculoskeletal system diseases development, in particular, osteoarthritis (OA). The search for effective methods for OA treating is an urgent task of molecular gerontology. The purpose of this work is to characterize the SASP of chondrocytes and to conduct a comparative assessment of the effect of AED peptide and the cartilage polypeptide complex (CPC). It was found that chondrocyte's SASP is characterized by an increase of the synthesis of p16, p21, p53 pro-apoptotic proteins, TNF-α, IL-1α pro-inflammatory cytokines and a decrease of Sirt1synthesis. Peptides AED and CPC normalize the synthesis of molecules that form SASP of chondrocytes. This effect may explain their geroprotective effect and effectiveness in studies of various pathologies of the musculoskeletal system, including OA.

[Diagnosis of fragility and age resilience from a dynamical systems perspective.]

The concepts of fragility and resilience are often used together to describe elderly people with reduced physical activity. While fragility, which develops with the aging of the body, is a biological syndrome of a decrease in the stressors response resulting from cumulative regression in many physiological systems, and age related a comprehensive assessment of the ability resistance to stress. In this regard, it is important to develop systems and scales for the identification groups of risk among the elderly. The complexity of the solution lies in the fact that the study of fragility and physical resilience is interdisciplinary, primarily related to the health and increase in the active life of older people. The review describes theories based on the mechanisms of physiological aging, among them the theory of a decrease in the ability to stress, in which stress-related to diseases. The cycles of the development of fragility and a decrease in physiological reserves are considered, and, as a consequence, a change in reactivity to stress, which leads to the development and progression of diseases. The article presents data on homeostatic dysregulation in the accumulation of cumulative deficiency and related changes in heart rate variability, which allows early diagnosis of stressors in the elderly. These data will be useful for the development and implementation of preventive measures aimed at improving the quality of life and resistance to stress factors in elderly and senile people.

[AEDG peptide regulates human circadian rhythms genes expression during pineal gland accelerated aging.]

Night work provides biorhythms desynchronization, disorder of melatonin-producing function and accelerated pineal gland aging. One of the promising geroprotectors restoring the pineal melatonin synthesis is the AEDG (Ala-Glu-Asp-Gly) peptide. AEDG peptide increases in 1,7 times the 6-sulfatoxymelatonin (6-SOMT) excretion in the urine of middle-aged people. Moreover, AEDG peptide normalized circadian Clock and Csnk1e genes hyper expression in leukocytes in 1,9-2,1 times and increases the Cry2 gene hypo expression in peripheral blood lymphocytes in 2 times in people with reduced melatonin-producing epiphysis function. The geroprotective effect of the AEDG peptide is based on its ability to restore the epiphysis melatonin-producing function by means regulation of human circadian genes expression.

[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.

[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).

Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland.

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.

[Effects of vascular peptide bioregulator on cerebral microcirculation of old hypertensive rats].

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.

[Results of troponin I testing by high sensitive method in three age groups of healthy population].

Article is about troponin I testing by high sensitive method in healthy population group. 165 people (employees of hospital) were examined, 71 % - women and 29 % - men. Inclusion criteria were as follows: absence of active complaints at the time of health examination and during the previous 30 days. All the examinees were divided into three age groups: 18-34 years (middle age, I period), 35-54 years (middle age, II period), above 55 years (old age). Research of correlation between cardiac troponin I and age of healthy population group was the main aim of investigation.

Effect of Polypeptides on Cell Proliferation and Apoptosis during Aging.

Polypeptide complexes derived from the bronchi, blood vessels, muscles, kidneys, ovaries, testes, and retina stimulated the processes of cell renewal in organotypic cultures of the corresponding organs of young and old animals. A correlation between the intensity of regeneration and animal' age was revealed. The polypeptide complexes reduced the expression of apoptotic factors p53 and caspase 3 and increased the expression of proliferation protein Ki-67. These results provide the basis for further study of the polypeptide complexes as stimulators of regenerative processes in different tissues during ageing.

[Functional cumulation of influence of vascular peptide bioregulator on microcirculation in the brain cortex of spontaneously hypertensive rats.]

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 «Slavinorm¼ 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 «Slavinorm¼ 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.

Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats.

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 microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times.

[The investigation of blood cells of middle and old age in patients with bronchial asthma and chronic obstructive pulmonary disease by atomic force microscopy. Similarities and differences with the biological animal model].

The investigation of reactive changes of blood cells in such diseases as COPD or asthma in people of different age groups is the very difficult problem. Simulating the same conditions in animals that occur in humans with these diseases can serve as a reliable practical model. It is possible because the changes which take places at the cellular level in animals might reflect a similar trend in the human body.

[OPTIMIZATION OF REPARATIVE OSTEOGENESIS JAWS ON AGING (PRECLINICAL STUDIES)].

The article presents the results of pre-clinical studies of the possibility of optimization of reparative osteogenesis in postoperative bone cavities of the jaws in old rats with a peptide bioregulator of Kartalaks. Using histological and morphometric methods in the experimental study, it is shown that the use of Kartalaks positive effect on the course of the process of reparative osteogenesis of the mandible in old rats. The features of the Kartalaks drug investigated for optimization of reparative osteogenesis jaw during aging. It is found that by using Kartalaks in old animals to 30 days before the surgical intervention, the process of reparative osteogenesis standard defect of mandible occurs at early stages (before 30 days), similar to the control. The deadlines for 60-120 days from the beginning of the experiment using the peptide bioregulator Kartalaks, noted the formation of a complex regenerate tissue containing a smaller proportion of connective tissue and cartilage, as well as more advanced remodeling of newly formed bone tissue compared with the control group, and older animals who received the drug after performing surgery.

[Diagnostics of the changes arising in an oral cavity at oncological sick senior age groups (review)].

Article is devoted to the changes happening in an oral cavity and in oral liquid under the influence of preparations of the oncological diseases used for treatment. Considering that research of oral liquid belongs to one of noninvasive methods of diagnostics and can be used with success for definition and correction of conditions of the mucous membrane of an oral cavity at the patients of advanced and senile age passing polychemotherapeutic treatment, this type of research is the extremely perspective for a gerontostomatology.

[The effect of vascular peptide bioregulator on the microcirculation in the brain cortex of old rats].

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.

["Protein of senility" CCL11, "protein of juvenility" GDF11 and their role in age-related pathology].

The paper presents the latest literature data on the structure and functions of «protein of juvenility¼ - CCL11 and «protein of senility¼ - 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 age¼. 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.

[POLYPEPTIDES INFLUENCE ON TISSUE CELL CULTURES REGENERATION OF VARIOUS AGE RATS].

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