Ageing (as known as eldering, senescence) is a genetically and epigenetically programmed pathophysiological process. Velocity of biological ageing is defined as balance between alteration and reparation of body structures. According to last World Health Organization (WHO) highlights ageing still stays an extremely actual scientific, social and demographic problem: in 2020 total number of people older than 60 years and older was 1 billion people; in 2030 future number may be 1,4 billion people, in 2050 - 2,1 billion people. Absence of single universal theory of aging nowadays is reason for scientifical and clinical collaboration between biologists and doctors, including endocrinologists. Designing of potentially effective newest anti-ageing strategies (such as natural/synthetic telomerase regulators, mesenchymal stem cells etc.) is of interest to scientific community. The aim of present article is a review of modern omics (genomic, proteomic, metabolomic) ageing mechanisms, potential ways of targeted prevention and treatment of age-related disease according to conception of personalized medicine. Present review is narrative, it does not lead to systematic review, meta-analysis and does not aim to commercial advertisement. Review has been provided via PubMed article that have been published since 1979 until 2022.

The article reviews the main properties of the cornea and the mechanisms of its physiological regeneration and repair in response to damage and describes the most promising methods of treatment aimed at stimulating limbal stem cells and based on the use of native tissues of perinatal origin, umbilical cord mesenchymal stromal cells, and cell-free therapeutic products.

Currently, there is no effective method of treating complete spinal cord intersection. One of the promising experimental approaches is substances promoting repair and fusion of axonal membranes.

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.

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.

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

In this article, we celebrate the life and scientific contributions of the exceptional theoretical gerontologist Alexey Matveyevich Olovnikov (1936-2022), who is renowned for his visionary hypothesis regarding the role of telomeres in aging. He postulated that the ends of linear chromosomes cannot be completely replicated, which explains the limited potential of somatic cell divisions. He also predicted the presence of a specialized DNA polymerase that lengthens telomeres in germ, cancer, and stem cells. These and other aspects of telomere biology have been confirmed and are now the foundations of modern gerontology. Alexey proposed several hypotheses on aging, biorhythms, morphogenesis and evolution, all of which are striking and extraordinary, much like their author.

Therapeutic angiogenesis is a trend of treatment based on stimulating the growth of new blood vessels to fill the perfusion deficiency and thereby restore the function of a damaged organ. It is especially important in case of inefficiency or impossibility of surgical methods to re-establish perfusion of ischemic tissues. This method can also be effective at the initial stages of ischemic processes, including for the prevention of disease progression and the development of complications.Most technologies for stimulating angiogenesis are based on the creation of a high concentration of angiogenic growth factors. Physical and chemical methods can be used to stimulate the production of endogenous proangiogenic molecules. However, the clinical status of patients often implies the presence of defects in the endogenous mechanisms of regulation of angiogenic processes, therefore, the main trend in research is the development of methods for adequate repair of the mechanisms of regulation of angiogenesis. This review presents data on modern technologies of therapeutic angiogenesis, separately considering the state of the art of methods based on therapy with recombinant growth factors, encoding genes, as well as cells and their derivatives, also discussing peculiarities, advantages, and limitations of each of the methods.

The CD133 protein is a large transmembrane glycoprotein. Despite multiple studies, the role of CD133 protein in cells is still poorly understood. Nevertheless, there is an association of CD133 protein with neoplastic transformation. This review summarizes data on CD133 protein, its structure, regulation of expression, molecular interactions and representation in cells that have undergone malignant transformation. Available data suggest that CD133 may have a great potential for predicting survival in various solid tumors. This protein can also be a marker of glioma.

The problem of current treatment approaches to brain gliomas is short-term life expectancy in these patients. Apparently, it is required to change treatment approach via analysis of glioma stem cells rather cells with overexpression of marker genes. This review is devoted to similarities and differences between neurogenesis and neuro-oncogenesis characterized with molecular markers (CD133 as an example). The role of tumor stem cells and their relationship with neural stem cells are considered regarding development of glioma. The authors analyzed CD133 as a marker of glioma stem cells. In the future, stem cells will be important target for eradication during target therapy. A single molecular marker cannot characterize tumor stem cells as supported by CD133 studies. A set of molecular markers specific for certain cell type is required, and their combination will provide more accurate establishment of tumor stem cells.

This review is devoted to the prospects for the use of fundamentally important approaches and methods for the correction and therapy of genodermatoses, a group of inherited skin diseases. The greatest number of methods was applicable for the group of inherited epidermolysis bullosa. Gene replacement using viral and non-viral methods of delivery to cells has been replaced by genome editing using programmable nucleases used both in vitro and in vivo. The focus is on more widely used methods applied in vitro to various cell types. The description of the methods used is classified based on the use of DNA break repair pathways: the canonical non-homologous end-reconnection pathway-cNHEJ, and directed homologous recombination-HDR. The choice of editing strategy depends on the type of mutation causing the disease, the type of mutation inheritance, and the nucleotide environment of the mutation. Animal disease models obtained by genome editing are considered. The experience of developing methods for editing the genome and their application for the treatment of genodermatoses, previously recognized as incurable, is summarized.

Obesity and type 2 diabetes mellitus (DM 2) are two interrelated metabolic diseases widespread throughout the developed world. However, up to 30% of individuals with a long history of obesity do not have a carbohydrate metabolism disorder. This article presents the results of a multi-year study of adipose tissue biology in obese individuals with DM 2 compared with individuals with the same history of obesity without DM 2. Comparative analysis of hormonal, cellular, and genetic factors in two groups of patients showed that DM 2 occurs in individuals with abnormal proliferation and adipogenic differentiation of mesenchymal stem cells (MSCs) of adipose tissue. It leads to adipocyte hypertrophy and inflammatory infiltration of adipose tissue macrophages, resulting in increased insulin resistance and diabetogenic effects. These disorders are due to abnormal expression of genes responsible for the proliferation and adipogenic differentiation of MSCs. The study of the possible reversibility of abnormal changes in adipose tissue MSCs in obese patients after significant weight loss and DM 2 remission appears to be a promising research direction. The ability to control adipose tissue progenitor cells may represent a new target for treating and preventing metabolic disorders in obesity.

The article presents scientific evidence that new neurons from progenitor cells throughout life in almost all animals with a nervous system are an integral component of neuronal ontogenesis and plasticity.It has been shown that there are neural stem cells in the brain that give rise to adult neurogenesis, occurring primarily in the dentate gyrus, a subregion of the hippocampus important for learning, memory, and emotion. With age, there is a decrease in adult neurogenesis, which is associated with a decrease in cognitive functions. Newly formed neurons and «immature» neurons together constitute a potential reservoir of young cells («brain reserve») that can be used to prevent aging and/or delay the onset/reduce the impact of neurological disorders.The possibility of using neurogenic processes for therapeutic purposes to reduce pain and improve the quality of life of patients is implied.

Retinal diseases accompanied with the dysfunction or death of the retinal pigment epithelial (RPE) cells are widespread, hard to treat, and appear to be a leading case of visual loss and blindness among the persons older than 55 years. Transplantation of RPE cells derived from the induced pluripotent stem cells (IPSC-RPE) is a promising method of therapy for these diseases. To ensure the transplant survival instant follow-up is required. It can be based on biochemical analyses of tear fluid that can be easily non-invasively collected. For the post-transplantation process monitoring we have choosen such polyfunctional bioregulators as α2-macroglobulin (α2-MG) and endothelin-1 (ET-1). RPE atrophy in New Zealand Albino rabbits was modeled via the subretinal injection of bevacizumab. IPSC-RPE in suspension or as a monolayer on the scaffold were transplanted subretinally 1 month after the injection. α2-MG activity and ET-1 concentration in tears were estimated during the first month and after 2, 3 and 7 months after transplantation. On the 7-14 days after transplantation α2-MG activity increased in tears of the both operated and controlateral eye probably as a reaction on the corticosteroid therapy. In 50% rabbits there was one more increase after 2-3 months that could be due to the immune inflammation. Concentration of ET-1 in tears decreased dramatically on the 7-14 days and 7 months after transplantation, and it could have an influence upon the retinal vassal tone. The data obtained show that estimation of bioregulators in tears can help monitoring local metabolic processes after RPE transplantation that is necessary for the opportune, reasonable and focused medicamental correction of post-transplantation process.

To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy.

To date, no modern methods of treatment allow overcoming malignant potential of glial neoplasms and significant increase of survival. Analysis of glioblastoma radioresistance using cancer cell cultures is one of the perspective directions, as radiotherapy is standard and available treatment method for these neoplasms. This review summarizes current studies identifying many factors of radioresistance of glial tumors, such as hypoxia, microenvironment and metabolic features of tumor, stem cells, internal heterogeneity of tumor, microRNA, features of cell cycle, DNA damage and reparation. We obtained data on involvement of various molecular pathways in development of radioresistance such as MEK/ERK, c-MYC, PI3K/Akt, PTEN, Wnt, JAK/STAT, Notch, etc. Changes in activity of RAD51 APC, FZD1, LEF1, TCF4, WISP1, p53 and many others are determined in radioresistant cells. Further study of radioresistance pathways will allow development of specific target aptamers and inhibitors.

Many cells are capable of maintaining viability in a non-dividing state with minimal metabolism under unfavorable conditions. These are germ cells, adult stem cells, and microorganisms. Unfortunately, a resting state, or dormancy, is possible for tuberculosis bacilli in a latent form of the disease and cancer cells, which may later form secondary tumors (metastases) in different parts of the body. These cells are resistant to therapy that can destroy intensely dividing cells and to the host immune system. A cascade of reactions that allows cells to ener and exit dormancy is triggered by regulatory factors from the microenvironment in niches that harbor the cells. A ratio of forbidding and permitting signals dictates whether the cells become dormant or start proliferation. The only difference between the cell dormancy regulation in normal and pathological conditions is that pathogens, mycobacteria, and cancer cells can influence their own fate by changing their microenvironment. Certain mechanisms of these processes are considered in the review.

To evaluate therapeutic efficacy of mesenchymal stem cells in patients with severe acute pancreatitis.

Auditory neuropathy spectrum disorder (ANSD) is a specific auditory disorder caused by dysfunction of periphery part of the auditory system, in which the function of the outer hair cells is preserved, but the afferent input at the cochlear level suffers due to the pathology of the inner hair cells, neurons of the spiral ganglion and/or the auditory nerve, as well as synaptic contact between them. As a result, a specific condition is formed, in which a patient's otoacoustic emissions and/or cochlear microphonics are present, auditory brainstem responses are abnormal or absent, the discrepancy between the hearing level and the electrophysiological data, poor speech perception which may not correlate with the hearing thresholds. ANSD is a multifactorial disease. One of the main risk factors is perinatal pathology and, in particular, prematurity. The possible factors associated with prematurity that provoke the onset of the disease, features of the pathogenesis, clinical and audiological peculiarities of ANSD in premature infants, contemporary approaches to the habilitation of such patients are discussed in the article. The necessity of an individual, patient-oriented approach to the treatment of premature infants with ANSD is substantiated; such an approach should be based both on the genesis of the disorder, taking into account possible points of lesion in the auditory system, and the developmental peculiarities of a premature baby considering the presence of concomitant diseases associated with prematurity. In the article attention is focused on the main directions of habilitation work with such children, including a multidisciplinary approach, regular careful monitoring of the auditory, speech and language skills, intensive psychological and speech therapist support, the choice of an adequate way of intervention and its improvement as necessary.

To develop and evaluate the results of the modified surgical technique for transplantation of retinal pigment epithelium (RPE) differentiated from human induced pluripotent stem cells (iPSC-RPE) in the form of a cell suspension into the subretinal space of rabbits with previously induced RPE atrophy.