[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.

[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.

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.

[Prospects of buccal epithelium application for noninvasive diagnosis of coronary heart disease in people of different age.]

Cardiovascular diseases caused by atherosclerosis, in many countries of the world are one of the most important social and economic problems due to the high morbidity and mortality rate of the working population. Recently, the immunological theory of atherosclerosis and coronary heart disease (CHD) has been actively developed, and the search for markers of inflammation characterizing immuno- and atherogenesis has been conducted. Buccal epithelium (BE) can be used as biological material for in vivo molecular-cellular studies, allowing to diagnose CHD by inflammation markers. The purpose of the work was a comparative study of the expression of IL-1ß, IL-6, IL-10, MCP-1 and GDF-15 in BE in patients of different ages with CHD and without cardiovascular disease. The material of BE in healthy donors and patients with 2nd stage CHD was divided into groups according to age classification of the WHO: the 1st - middle-aged people (45-59 years) and the 2nd - elderly people (60-74 years). Control material was obtained from people of middle and old age without cardiovascular disease. According to the immunocytochemical study, the area of IL-1ß expression in BE is 3 times higher in middle-aged people with CHD, and in 4,4 times higher in elderly people compared to healthy individuals of the same age group. The area of IL-6 expression in middle-aged and elderly people with CHD was in 7,9 and 7,4 times higher, respectively, than in the control group. In middle-aged and elderly patients with CHD, IL-10 expression was in 1,6 and 2,8 times higher, respectively, compared to healthy donors of the same age group. The expression of MCP-1 in BE of middle-aged and elderly people in normal and ischemic heart disease did not differ. GDF-15 expression is in 6,8 and 6,6 times higher in middle-aged and elderly people with CHD than in healthy people of the same age. The findings showed that the expression of the cytokines IL-1ß, IL-6, IL-10 and GDF-15 increase in BE in patients with CHD of middle-aged and elderly people compared with persons of the same age group without cardiovascular disease. Thus, BE can serve as an informative material for noninvasive molecular diagnosis of CHD in people of different ages.

[Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аß42 in CSF in case of AD, but CSF taking may have a number of side effects. Less traumatic taking of sampling tissues for the diagnosis of AD is in use of epithelium biopsy and blood portion. An increase in the expression of the hyper phosphorylated form of τ-protein is shown in blood lymphocytes of AD patients. An increase in the content of high molecular weight forms of phosphorylated t-protein and amyloid precursor protein-APP was also revealed in blood platelets of AD patients. Changes in the amount of 2 miRNA families - miR-132 family and miR-134 family were revealed in blood cells 1-5 years before the manifestation of clinical signs of AD. An increase in the concentration of bound calcium, synthesis of peptides Aß40 and Aß42, τ protein was observed in AD skin fibroblasts. In the olfactory and buccal epithelium an increase in the expression of hyper phosphorylated form of τ-protein and Aß peptide was detected in patients with AD. Verification of AD markers in peripheral tissues for biopsy have the important significant for life diagnostics, prevention and and target AD treatment.