In people over 60 years, the most common diseases are the cardiovascular system and geriatric syndromes. Dyslipidemia and hyperglycemia are traditional cardiovascular risk factors. However, their impact on the major geriatric syndromes development among people over 60 years remains unclear. The relationship between the presence of diabetes mellitus type 2 and the development of frailty, sarcopenia, cognitive impairment depends on age. With increasing age, the influence of chronic hyperglycemia on geriatric syndromes decreases and in centenarians it acquires a neutral role. Recent studies have shown that in people over 60 years old low HDL levels are associated with the development of frailty, sarcopenia, cognitive impairment.

Extracellular vesicles (EVs) are considered to be the most significant component of the mesenchymal stromal cell (MSC) secretome. Vesicles carry a set of proteins, bioactive lipids, and nucleic acids in their composition, protecting them with a lipid bilayer, and when taken up by target cells, they can demonstrate persistent regenerative effects. However, many researchers have shown that other components of the conditioned environment, besides BB, are also involved in the function of MSCs. Thus, to elucidate the mechanisms of regenerative effects of MSCs, it is important to evaluate the contribution of BBs to these processes.

BBs participate in intercellular communication, transferring proteins, bioactive lipids and nucleic acids from one cell to another. BBs produced by stem cells can deliver important information to target cells for tissue regeneration after damage [1].

The vast majority of articles studied in the course of this review reveal similar issues, such as vesicle biogenesis, their contents, size classification, and participation in intercellular interaction. Also, the fusion ligand-receptor interaction of vesicles with the recipient cell has been discussed in sufficient detail. Only a few articles mention the specificity of vesicle-cell interaction. However, when considering the given examples, one can notice that, in the end, the detailed description of the mechanism of vesicle recognition by a cell is reduced to the description of the ligand-receptor pair interaction.

Raising the question of the specificity of vesicle-cell interaction, we decided to study in detail the ligand-receptor pairs mentioned in most articles. Perhaps, the specificity of vesicle-cell/tissue interaction is not determined by their biogenesis, membrane composition, and internal composition, but merely by the specific electrostatic field of the tissue that attracts vesicles with appropriate charge characteristics [2, 3, 4].

On this basis, it can be assumed that specificity, as such, does not exist, but there is a volume distribution of differently charged vesicles in the electrostatic field of tissues [5].

To answer the question about the possibility of vesicle distribution, it is proposed to create a model predicting the biodistribution of BBs depending on their total surface charge. For this purpose it is necessary to prepare training and test (validation) samples.

Tabular data will be used for analysis, where the object for each record will be a molecular component of the extracellular vesicle membrane, and the attribute will be the location of its distribution confirmed by open data (the number of attributes may vary) (Table 1). Data collection is complicated by the lack of readymade arrays. The table is formed manually from the volume of a pre-prepared sample of literature on the given subject. The approximate size of the table is 2 (or more) * 1000.

For direct training of the model, the training (training) sample, on which the algorithm parameters are optimised, will include all cases of distribution prediction based on the knowledge of electrophoretic mobility of particles in a charged field and electrostatic effects. Seventy per cent of the data obtained will be used to create this sample (90% if insufficient data is available). To verify the accuracy of the model and to control model overfitting, the test sample will consist of experimentally validated examples of vesicle distributions. To create this sample, 30% of the obtained data will be used (10% if insufficient data).

The next step is to determine the most appropriate machine learning algorithm. After studying publications devoted to similar tasks, it was decided to use Random Forest (RF) machine learning algorithm as the most suitable for solving this type of problems. We plan to use Random Forest architecture, where each tree has Gini index as a quality criterion of tree branching, the depth of each tree will be considered as a hyperparameter, the optimum of which will be selected by early stopping, limiting the depth of the tree, setting the minimum acceptable number or cutting off branches.

Once the model is obtained, the available data on the composition of extracellular vesicles of MSCs cultured in the laboratory will be verified. The prediction result will then be validated experimentally.

Relevance. Currently, the use of anticonvulsants is widely accepted in the treatment of neuropathic pain. Gabapentin, a drug within this group, is renowned for its effectiveness as it shares similarities with the neurotransmitter gamma-aminobutyric acid (GABA). In addition to enhancing GABA synthesis, gabapentin affects NMDA receptors, blocks the α2-δ subunit of calcium channels, inhibits glutamate synthesis and transport, reduces the release of monoamines, and substance P.

Aim. To study the effect of gabapentin in the complex treatment of chronic neuropathic low back pain syndrome in geriatric patients.

Materials and Methods. We conducted a study on the use of gabapentin in the comprehensive treatment of 28 geriatric patients aged 65 to 98 years, who had glomerular filtration rate (GFR) values of at least 30 mL/min according to the Cockcroft-Gault formula, and chronic neuropathic pain syndromes in the lower back, constituting the main group (MG). The control group (CG) consisted of 20 patients aged 65 to 97 years with a similar clinical presentation. The inclusion criterion was the presence of sleep disorders in patients associated with the presence of lower back pain, as assessed by the «Subjective Sleep Characteristics Assessment Questionnaire» — SSCAQ.

Results. The average pain score in the MG and CG was 8.7 ± 1.3 and 8.1 ± 1.6 on the Visual Analogue Scale (VAS), respectively. The average sleep disturbance score in the MG and CG was 13.6 ± 2.1 and 12.4 ± 3.3 on the SSCAQ, respectively. All patients in both groups received standard treatment, including local, intravenous, intramuscular, and oral administration of analgesics, anesthetics, muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), and physiotherapy procedures. In addition, patients in the MG received gabapentin, starting from the first day of treatment, with a daily dose of 300–900 mg, taking into account the signs of decreased GFR. The average dose of the medication in 80% of cases was 600 mg per day, administered as 300 mg twice daily. Two patients in the main group were excluded from the study due to the side effect of foot edema at a dose of 600 mg per day.

The intensity of the pain syndrome significantly decreased after treatment in both groups, averaging 2.7 ± 0.8 in the MG and 4.2 ± 1.1 in the CG, i.e. decreased by 78.07% and 50%, respectively (p < 0.01). Sleep disorders were on average 23.4 ± 4.8 in the MG, and 16.9 ± 4.3 in the CG, i.e. decreased by 41.9% and 26.6% (p < 0.01). The duration of inpatient treatment was 16.8 ± 2.4 days in the group and 19.1 ± 3.7 days in the control group. The drug was continued on an outpatient basis in selected dosages.

Conclusion. The research has shown that a daily intake of 600 mg of gabapentin, divided into two 300 mg doses, is the recommended dose for treating chronic neuropathic pain syndrome and sleep disorders in elderly patients aged 65 to 98. Factors to consider when administering gabapentin to older patients include adjusting the drug dose according to routinely monitored renal GFR, using the drug in a lower dose resulting in improved treatment outcomes thus increasing overall effectiveness from treatment, providing faster relief from neuropathic pain in the lower back, prolonged sleep, limiting the duration of inpatient treatment, maintaining adherence to various outpatient care over a long period.

Relevance. Treatment of chronic interstitial cystitis is one of the acute problems of modern urology. The development of new treatment options for this disease is necessary to optimize results and improve the quality of life of patients.

Aim. To analyze the results of photodynamic therapy for chronic interstitial cystitis in geriatric patients.

Materials and methods. The study was conducted on 45 patients over the age of 65 with chronic interstitial cystitis to examine the short and long-term effects of treatment. The main group consisted of 25 patients who received intravesical photodynamic therapy in combination with traditional antibacterial and anti-inflammatory treatment. In turn, the control group enrolled 20 patients who were treated with traditional therapy only. Patients must have met the following inclusion criteria to be eligible for participation in this study: the presence of chronic interstitial cystitis manifestations at least 3 times a year, morphological confirmation of interstitial cystitis. The study used clinical, laboratory, and instrumental research methods. To objectively assess the clinical symptoms of the disease initially, in the immediate and long-term periods after the start of treatment, the index of symptoms/problems of interstitial cystitis was used. Prior to the study and treatment, patients engaged in a discussion regarding the purpose and outcomes of diagnostic and therapeutic procedures, as well as their potential benefits and risks. Following this, the patients provided their informed consent by signing the necessary documents. For photodynamic therapy, the photosensitizer Photoditazine was administered intravenously 2 hours before the procedure at a dose of 0.8 mg/kg. Cystoscopy was performed. Using a quartz-polymer light guide, laser irradiation of the mucous membrane of the bladder was carried out with a wavelength of 661 nm, in a continuous mode, with a power of 2 W, an energy density of 25 J/ cm2, and an exposure time of 30 minutes. The dynamics of clinical and laboratory (leukocyturia, bacteriuria) parameters were assessed.

Results. In terms of clinical progress, the main group saw improvement after three to four days, while the control group showed improvement after five to seven days of treatment. Leukocyturia in the main group decreased significantly on the third day, disappeared on the seventh day, meanwhile in the control group it remained at the upper limit of normal. On the third day of treatment in the main group, bacteriuria decreased to 104 CFU/ml, in the control group — to 106 CFU/ml. On the seventh day, bacteriuria was not detected in the main group, while in the control group it remained at the upper limit of normal. The duration of hospital stay for patients in the main group was 7.5 ± 0.2 days, for the control group — 10.8 ± 0.3. Long-term results of treatment over a period of 15 to 22 months in the main group showed the absence of clinical and laboratory manifestations of the disease. In the control group, the manifestation of chronic interstitial cystitis was noted in 45% of patients and clinically significant leukocyturia and bacteriuria.

Conclusions. The results of the study demonstrated a higher effectiveness of photodynamic therapy in combination with antibacterial and anti-inflammatory treatment of patients with chronic interstitial cystitis compared to traditional methods.

Introduction. Violation of all types of metabolism leads to the development of purulent-necrotic lesions of the feet in more than 25% of patients with diabetes mellitus. Often these patients receive repeated courses of antibiotic therapy, which sometimes leads to the formation of antibiotic intolerance, as well as the development of resistance of microorganisms to most antibiotics. The presence of diabetic angiopathy and severe purulent infection on the foot may hinder the penetration of certain antibacterial drugs into the purulent site. Microbiological studies, both on the wound surface and deep in the tissues, most often reveal a mixed microflora that is resistant to most antibiotics. In most cases, with a complex wound configuration or the development of a severe surgical infection, it is not possible to completely transform the lesion into a clean wound during one operation. This leads to the need to perform repeated surgical treatments, respectively, to an increase in the number of surgical interventions and lengthening the treatment period. The use of hydrosurgical technologies during surgical treatment in the complex of laser photodynamic therapy (PDT) of wounds in the postoperative period provides the most complete and rapid cleansing of wounds from necrosis, fibrinous-purulent plaque, which is associated both with sterilization of the wound by laser radiation and the weakening of disturbances in the microvasculature, and stimulation of regenerative processes due to activation of oxygen transport in the developing granulation tissue.

Aim of the study was to evaluate the efficacy of the combined use of laser PDT and hydrosurgical system (VersaJet) in the complex treatment of purulent wounds in patients with diabetic foot syndrome (DFS).

Materials and methods. We proposed the treatment of purulent wounds in patients with diabetic foot syndrome based on the combined use of PDT and hydrosurgical technologies to stimulate regeneration and sterilization of wounds. The work summarizes the experience of treating purulent wounds in 44 patients with diabetic foot syndrome. The age of the patients ranged from 65 to 89 years, the area of the wound surface was from 10 to 25 cm2. In group 1, 21 patients (control) received traditional treatment; the main group included 23 patients whose wounds were treated using laser PDT and a hydrosurgical system.

Results. As a result of treating wounds with laser PDT together with a hydrosurgical system, resolution of inflammatory phenomena on the foot in patients of the main group was noted 4–9 days earlier than in the control. A decrease in microbial contamination of wound tissue below the “critical level” in patients of the main group was detected on days 5–7 after the start of treatment, and in the control group on days 10–15. Cleansing of wounds, the appearance of granulations and marginal epithelialization in patients of the main group were detected, respectively, after 5.2 ± 0.5; 4.8 ± 0.4 and 5.8 ± 0.5 days, in the control group — after 10.2 ± 0.8; 9.8 ± 0.8 and 12.6 ± 1.1 days.

Conclusions. The analysis of the results of clinical studies showed that the combined use of a hydrosurgical system and the addition of local treatment of purulent wounds of soft tissues with laser PDT promotes accelerated regression of inflammatory processes in the wound, reduces the time it takes to cleanse wounds from purulent-necrotic masses and non-viable tissues, accelerates the appearance of granulation tissue and the onset of marginal epithelization, which, in turn, creates favorable conditions for performing plastic surgeries — autodermaplasty and the application of primary or secondary sutures and leads to rapid wound healing.

In addition to population ageing, one of the causes and most important problems facing the world today is the increase in age-related diseases such as cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM) which inevitably leads to the development of vascular wall changes and related micro- and macrovascular complications. Numerous experimental and clinical studies have pointed out to the role of glucose impairment in accelerating vascular wall changes, the speed and severity of these changes depends not only on environmental and genetic factors, but also on individual metabolic characteristics.

Among the many reasons for dissimilar rates of vascular alterations among patients with insulin resistance (IR) and T2DM is considered to be contributed by initially different «genetic protection» of the arteries from the influence of external negative factors. Replicative cell aging and its role in the development of vascular changes play an important role in these processes. Telomere length (TL) and telomerase activity (AT) are two vital biomarkers known as the "molecular clock" that regulate the lifespan of cells and mark the process of replicative cellular aging.

The link between vitamin D3 deficiency and the development and prognosis of numerous chronic non-communicable diseases has become a topic of significant interest in the world's scientific literature. Vitamin D3 is known to be involved in maintaining immune homeostasis, and its role in the polymorphism of enzymes involved in the pathogenesis of inflammatory processes is important. Recent literature has demonstrated the role of vitamin D not only in regulating calcium levels, but also in leveling chronic systemic inflammation, improving insulin sensitivity, reducing risk of T2DM development, obesity and autoimmune damage β-pancreatic cells, cardiovascular risk. The study of vitamin D influence on the development of main artery wall changes in T2DM and IR, and its association with telomere biology, holds significant relevance.

Relevance. The projected increase in the number of patients with glaucoma, late detection of the disease at an advanced stage with significant irreversible loss of visual function, leads to an expected rise in the number of patients with sensory deficits and subsequent disability. Considering the stage of the disease, the need to preserve residual visual function and reduce the frequency of instillations to improve the quality of life for such patients a special minimally invasive and highly effective approach to treatment is required. A crucial factor to consider is the evaluation of anesthesia risk, which involves factoring in comorbid conditions, a complex medical background, and potential interactions between different medications and the primary treatment.

Aim. To determine the efficacy of transscleral laser cyclocoagulation in older patients suffering from decompensated advanced and terminal glaucoma, and to evaluate its impact on their quality of life.

Materials and methods. The study included patients over 65 with decompensated advanced and terminal stages of glaucoma from the Ophthalmology Department of the War Veterans Hospital No. 2. Before the surgery, all patients received maximally tolerated hypotensive treatment. The surgical treatment, consisting of transscleral laser cyclocoagulation using a diode laser (wavelength 810 nm) with the Alcom Medika ALOD-01 device, was performed under local retrobulbar anesthesia (2% lidocaine solution, 4 ml). The average duration of the surgery was 10 minutes. The efficacy of the treatment was assessed based on the reduction in intraocular pressure (IOP), decreased frequency of instillations, perimetry results (kinetic perimetry before and 2 days after the surgery), and changes n visual function. Intraocular pressure measurements were taken on the 1st and 2nd days after the surgery, at 2 weeks, and then at 1 and 2 months postoperatively. During the three weeks following the laser intervention, no prostaglandin analogs were instilled in the operated eye.

Results. In all patients enrolled in the study, a reduction in intraocular pressure was observed to 40% on the first day, 60% on the second day, and 70% by the second week compared to the baseline level. At the end of the treatment, the frequency of instillations was reduced to 1–3 drops per day for all patients. Patients subjectively reported an improvement in visual function and pain relief. According to visual acuity measurements, an improvement of 1–2 lines on the eye chart was observed on average in patients with advanced glaucoma (80% of the examined patients). When assessing the results of perimetry, expansion of the peripheral visual field was observed in 80% of the examined patients or preservation of the visual field at the same level in 20% of the examined patients with advanced glaucoma. The level of intraocular pressure and improvement in visual function remained stable in 85% of the patients at the 2-month follow-up.

Conclusions. Surgical treatment using local anesthesia, minimal tissue trauma to the eye, and high efficacy in reducing intraocular pressure, improving visual function, and having a short rehabilitation period allow us to consider transscleral laser cyclocoagulation as the treatment of choice for older patients with decompensated advanced and terminal stages of glaucoma.

Relevance. Many studies have confirmed an age-associated decrease in the level of insulin-like growth factor 1 (IGF-1), which contributes to changes in a number of hormonal and metabolic processes. However, there is insufficient information about what level of IGF-1 is optimal in old age and whether maintaining a certain concentration of IGF-1 can have a positive effect and be a protective factor. Data obtained on a unique cohort of centenarians is especially limited, which determines the relevance of this study.

Aim. The paper aimed to study the association between higher and lower levels of IGF-1 with biomarkers of hormonal and metabolic status and determine its role in the one-year prognosis of centenarians.

Materials and methods. As part of a cross-sectional study, a cohort of people aged 90 years and older. Serum IGF-1 levels were measured using a chemiluminescent assay. Differences in survival between the high and low IGF-1 groups were assessed based on the results of one-year follow-up. The study was approved by the local ethics committee (protocol No. 30 of December 24, 2019). Statistical data analysis was carried out using the R programming language version 4.2.2.

Results. The study included 2893 people aged 90 to 107 years who met the inclusion criteria. The mean age was 92 years; the median IGF-1 level was 99.6 ng/ml. According to the results of intergroup comparison, a significant relationship with the level of IGF-1 was shown by the level of insulin, glycated hemoglobin, total protein, albumin and C-reactive protein (p-value < 0.001). The group of participants with higher IGF-1 levels (above the median — 9.6 ng/ml) had significantly higher levels of total protein, albumin and glycated hemoglobin and lower levels of C-reactive protein and insulin. When constructing logistic regression models and adjusting for the level of physical activity, statistical significance remained only for the association of IGF-1 levels and laboratory parameters such as insulin, glycated hemoglobin and albumin. When analyzing the survival of participants with high and low IGF-1 levels, higher (above the median) IGF-1 values were found to be a protective factor for the survival of subjects aged 90 years and older.

Conclusions. According to the results, higher IGF-1 levels were associated with better 1-year survival in subjects aged 90 years and older. In addition, bidirectional associations between IGF-1 and laboratory markers such as albumin, insulin and glycated hemoglobin were found. A more detailed analysis of the identified associations to determine the optimal level of IGF-1 to maintain metabolic processes among centenarians in different populations is required.

Introduction. It is known that chronological age may differ from biological age. Unlike chronological age, which is quite easy to determine, biological age is rather a cumulative assessment of the morphological, physiological and biochemical states of many systems of the human body. The biological age includes both a genetic component and an ontological one, considering the lifestyle of a person and the amortization of his body. The calculation of biological age is a more complex and, at the same time, a personalized approach for assessing the state of an organism compared to chronological age. There is still no single formula for determining the biological age of a person, however, attempts have been made to create local estimates, usually considering the state of an organ or system in the body. One of such local assessments may be a study of the patient's cardiovascular system, and one of the most informative instrumental diagnostics is Echocardiography. As a rule, during Echocardiography, morphological and functional changes of the heart are evaluated, indicators reflecting wall thicknesses, the volume of chambers, velocity blood flow, etc. are calculated.

The aim of the work was to create and train a predictive model using a neural network algorithm to estimate biological age based on Echocardiography data.

Material & Methods. The study included Echocardiography data from 300 patients of The Russian Clinical Research Center for Gerontology (Pirogov Russian National Research Medical University) who do not have chronic diseases. The age of patients ranged from 23–82 years in women, and 25–72 in men. Statistical analysis was performed in the statistical environment R. Echocardiography marks that have a native estimate (cm, mm, l, ml) were subject to normalization for height (cm). Spearman's correlation analysis was used as a nonparametric test to calculate the strength of the association between variables (Echocardiography marks) and age. The studied dataset was divided into training and testing sets. As a model, the architecture of a fully connected neural network (FCNN) was created using the Keras library. The architecture of the model is a deep network containing 10 hidden layers. The metrics of model quality during training were MAE (Mean Absolute Error), MSE (Mean Square Error), RMSE (Root Mean Square Error), R2 (R-squared coefficient of determination), and ε_acc (ε-accuracy — epsilon accuracy, where ε = 10, i.e. ± 10 years is the spread at accuracy assessment).

Results. The first step was an assessment of the ability of the Echocardiography data to describe an age. For this purpose, a nonparametric correlation analysis was carried out for groups of men and women separately. Out of 48 indicators, the top 15 were determined, which demonstrated a correlation with age of more than 0.55 (in abs value). Of these, the most common study protocol includes 8: E_A, IVS, LV_PW, LV_CO, LV_EDV, RWT. As well as H_RWT and L_E_A, which are calculated from RWT and E_A, respectively. Since the correlation of the selected parameters varies in its strength depending on gender (however, it retains the direction of dependence), two models were built — for men and for women. As a result, based on these parameters, we identified possible combinations and trained models based on them in three modes: general, for men, for women. According to the training results, several models demonstrated the highest accuracy of age assessment. The best models were combined into 2 two final complex models for each sex. As a result, predictive age models provide five Echocardiography marks as input data: LV_CO (cardiac output, l/min), E_A (E/A ratio of maximum flow rates in the 1st and 2nd phases), RWT (wall thickness ratio), IVS (interventricular septum thickness, cm), LV_PW (posterior wall thickness of the left ventricle, cm), and their two derivatives H_RWT (RWT ≥ 0.42) and L_E_A (E_A < 1); height (cm) and sex of the patient. The models intended for age forecasting have the following qualities: MAE = 4.92, MSE = 38.33, RMSE = 6.16, R2 = 0.78, ε_acc = 0.88, in men; MAE = 5.09, MSE = 39.42, RMSE = 6.28, R2 = 0.77, ε_acc = 0.89, in women.

Conclusions. Thus, two models for predicting age in men and women were created and trained, using five Echocardiography marks as predictors.

Relevance. The study of aging processes is a fundamental task of modern science. Gerontologists all over the world have long been paying attention to the transcription factor Nrf2, which is often called the master regulator of aging.

Aim. To analyze data pertaining to the impact of Nrf2 on aging in human and non-human mammals.

Materials and Methods. Analysis of available information from PubMed database with no publication time limit.

Results and conclusions. Many studies have demonstrated the direct involvement of Nrf2 in cellular and organismal aging. The transcription factor Nrf2 controls the expression of genes involved in antioxidant response, redox homeostasis, detoxification of toxic compounds, mitochondrial biogenesis and many other processes. Activation of these genes protects cells from oxidative stress and the development of inflammation. Nrf2 activation increases the expression of hemoxygenase (HO-1), responsible for the degradation of pro-inflammatory free heme and the formation of anti-inflammatory compounds such as CO and bilirubin; NAD(P)H: quinone oxidoreductase (NQO1), which has antioxidant activities; the cytoplasmic form of the antioxidant enzyme superoxide dismutase-1 (SOD-1); and key enzymes of glutathione biosynthesis (Gclc, Gclm), which is a major cellular antioxidant. The absence of Nrf2 in knockout mice causes an uncontrolled inflammatory response: activation of innate immune cells, high production of cytokines, chemokines and reactive oxygen species - all these factors contribute to cell and tissue damage [1-4].

In aging organisms, Nrf2 activity decreases, and oxidative damage to biomolecules gradually accumulates, accompanied by the production of inflammatory cytokines and subchronic inflammation. Activation of the transcription factor Nrf2 can reduce oxidative stress and inflammation in animal models such as Drosophila and nematodes, thereby retarding the development of senescent changes. That said, there are very few data on the effects of Nrf2 activators on human and mammalian aging. It might be expected that stimulation of Nrf2 would also lead to an increase in their lifespan. Indirect evidence for this assumption is the increased level of Nrf2 activation in long-lived animals such as the naked mole rat. Experimental work on the age-related dynamics of changes in Nrf2 activity in animals and humans, as well as on the effect of long-term administration of inducers of the transcription factor Nrf2 on longevity and signs of aging should become an important area of research. At the same time, there is a possibility that long-term pharmacological activation of Nrf2 may lead to the development of serious side effects, because long-lived organisms are finely adapted to the consequences of such activation, while humans and many other mammals do not have such adaptations [4].

The thesis about the key role of Nrf2 in aging processes is extremely controversial. Nrf2 regulates the expression of several hundreds of genes carrying specific sequences in their promoters, called antioxidant response element, ARE. But aging produces complex multidirectional expression changes that are unique to different tissues and species. These changes only correspond to a small extent to the pattern of genes controlled by Nrf2. Thus, it cannot be concluded at this time that Nrf2 is a "master regulator of the aging process" [4-5].

Relevance. Recently there has been an increase in the population of older people suffering from cardiovascular diseases. At the same time, the need to prescribe effective anticoagulation therapy to prevent thromboembolic complications also increases. Oral anticoagulants (DOACs) are one of the main methods of treatment for such patients; however, this group is characterized by polypharmacy and polymorbidity, which increases the risk of developing drug interactions when using them. Thus, it is necessary to take into account the possible risks of developing side effects of drugs when using DOACs.

Aim to study drug interactions of direct oral anticoagulants in geriatric patients.

Materials and methods. The study was conducted on the basis of the War Veterans Hospital No. 2 of the Moscow City Health Department in the 2nd, 4th, 5th geriatric departments. The study included patients aged 65 and over with chronic kidney disease (CKD) 3B and receiving one of the DOACs (Rivaroxaban (R), Dabigatran etexilate (D), Apixaban (A)). The patients were divided into 3 groups. The sample was made of 109 patients during the hospitalization period from May to June 2023.

Results. 69 patients were enrolled for analysis, the mean age was 81.4 years ingroup P, A and 75.6 years in-group D, 26 men and 40 women. CKD stage 2 — 26, 3A st. — 23, 3B st. 15 patients respectively. The duration of therapy was up to 1 year — 9, from 1 year to 5 years — 44 and from 5 to 10 years — 5 patients. Complications during therapy were noted in five cases in the P, A — epistaxis group. All patients were prescribed an average of 12.04 drugs from various drug groups. The smallest group D was younger in age compared to groups Pand A, this is due to the criterion creatinine clearance, which for D is 30 ml/min and requires cancellation, while for P, A this criterion is 15 ml/min. P and A are metabolized by CYP3A4, and D by glucuronidation enzymes UGT2B15, UGT1A9, UGT2B7, as well as with the participation of P-glycoprotein. Among the drugs used, the following drug interactions were identified: inducer carbamazepine and inhibitors verapamil, amiodarone, dexamethasone, diltiazem, clotrimazole, metronidazole, spironalactone.

Conclusions in older patients, it is necessary to evaluate age, glomerular filtration rate, and duration of DOAC use. When using DOACs, interactions between drugs that are metabolized by cytochrome CYP3A4 and P-glycoprotein should be assessed, which may result in decreased or increased drug concentrations (inducer/inhibitor) and increase the risk of side effects. One of the typical adverse reactions is epistaxis.

Relevance. Cognitive changes are one of the most common diseases in older patients. Neurodegenerative, cerebrovascular, and metabolic disorders are the most important triggers for evelopment of cognitive dysfunction. Correction of risk factors, conducting screening (tests assessing the risk of falls and fractures (osteoporosis is the most common cause of falls in older people), the risk of developing cognitive impairment), assessment of physical health indicators (medication intake, medical history, the presence of exacerbations, decompensated conditions) carried out in outpatient clinic can help improve the quality and increase the life expectancy of older patients.

Aim. Assessment of cognitive impairment in geriatric patients in outpatient practice.

Materials and methods. The study was conducted on the basis of the Voronezh City Clinical Hospital № 1 as a part of the preventive campaign “Day of Older People,” in which 421 patients (69 men, 352 women), whose mean age was 68 ± 5.5 years, took part. Every patient underwent a risk evaluation for falls and fractures using the Frax scale, cognitive changes were screened with the MiniCog test and blood pressure (BP) was recorded. Statistical data processing was carried out using the Statistics program.

Results. In total 35% of patients had uncontrolled arterial hypertension (AH) (at the same time, number of patients who took medications regularly – 56%). An increase in blood pressure above 180/110 mm during a physical examination was also detected. When assessing cognitive changes, it was revealed that more than 50% of the studied patients experience significant difficulties in performing tasks, which may indicate the development of dementia of varying severity (in 26% – mild severity, 48% – moderate severity, 26% – severe severity ). When collecting anamnesis, patients also noted significant difficulties, which required more time when answering questions (32% were unable to name the medications they were taking, 68% had difficulty in orienting themselves in time, place, and their own personality). It was found that such disorders were observed more often in men (56% of cases). When assessing the risk of falls and fractures using the Frax scale, a high (35%) or very high (28%) 10-year risk of complications was noted, which may indicate the development of osteoporotic changes of varying severity. It was also revealed that the closest relatives of 30% of patients were diagnosed with a history of fractures of various locations, as well as taking glucocorticosteroids (p < 0.006).

Conclusions. A significant increase in risk factors for the development of pathological conditions in older patients (cognitive impairment - dementia, osteoporotic changes) was identified, which require further laboratory and instrumental diagnostics to verify the diagnosis. Assessment of risk factors at the outpatient level contributes to timely both non-pharmacological and medicinal correction (creation of a safe life, organization of a comfortable environment, cognitive training, prevention of the development of anxiety and depression, individual selection of medications, prevention of development of hypertension complications), which entails absolute improvement in the quality of life in geriatric patients.

Aim. This study aimed to investigate the associations between hormonal and metabolic status and geriatric syndromes in centenarians.

Materials and methods. The study was carried out at Pirogov Russian National Research Medical University together with the Federal State Budgetary Institution FMBA. The study group included participants aged 90 and older, for whom a comprehensive geriatric assessment was carried out with the past medical history, the use of geriatric scales and questionnaires (MMSE, SARC-F, MNA and others), as well as collection of blood samples for assessment lipid profile parameters, carbohydrate metabolism indicators, hormones, telomere length. Special attention was paid to the assessment of hormonal-metabolic status in participants aged 90 and older with frailty and associations between vitamin D levels and geriatric syndromes. The study was approved by the local ethics committee (protocol No. 30 of December 24, 2019). Statistical analysis and data visualization were performed using the programming languages R version 4.1.3 and Python version 3.9.

Results. A total of 3007 people who met the inclusion criteria were enrolled in the study. Frailty was found in 627 (82.6%) of 759 men and 2061 (91.7%) of 2248 women. It was found that a statistically significant inverse association with frailty had the following: 25-OH vitamin D levels (increasing the concentration of 25-OH vitamin D by 10 ng/ml reduced the odds of having SA by 11% (95% CI 0.0001%, 21%) , apolipoprotein A1 (a 10 mg/dL increase in apolipoprotein A1 concentration reduced the odds of having SA by 8% (95% CI 3%, 12%), albumin (a 10 g/L increase in albumin reduced the odds of having SA by 36% (95 % CI 12%, 53%) and free triiodothyronine (a 2 pmol/L increase in free triiodothyronine reduced the odds of having SA by 37% (95% CI 8%, 57%). The mean 25-hydroxyvitamin D level in the group was 9 ng/ ml, 86.7% of participants had 25(OH) D deficiency, 8.4% had insufficiency. According to the results of intergroup comparison, a significant association with the vitamin D level group was shown by malnutrition, sarcopenia and cognitive impairment. However, when adjusting for nutritional status, diet and physical activity, the statistical significance of the association of vitamin D levels remained only for cognitive impairment.

Conclusion. Low levels of 25-OH vitamin D, apolipoprotein A1, free triiodothyronine and albumin can be considered as possible biomarkers associated with the presence of frailty among people aged 90 and older. The preventive value of correcting these parameters deserves further study. Also, this study, for the first time in the Russian Federation, highlights the problem of vitamin D deficiency in the population aged 90 and older and its associations with the presence of geriatric syndromes. The obtained results on the association of vitamin D deficiency with cognitive impairment can become a starting point for subsequent intervention studies on the possibility of modifying this condition with nutritional supplements.

Intrinsic ability, a core concept of healthy aging, is defined by the WHO as “the sum of all the physical and mental abilities that a person can use at any given time.” Vital capacity is considered the primary physiological determinant of intrinsic vitality. To facilitate the measurement and monitoring of viability, a working group of WHO staff and twenty experts representing six WHO regions was convened to discuss and clarify the characteristics of viability and develop a clear operational definition of the concept. Potential biomarkers for measuring vitality have been identified and the following consensus working definition has been developed: Vitality is a physiological state (due to normal or accelerated biological aging processes) resulting from the interaction between multiple physiological systems, as reflected in energy and metabolism , neuromuscular function, as well as immune function and the body's response to stress.

The concept of assessing health status implies, first of all, the creation of a socalled comprehensive gerontological assessment, including assessment of domains of functional, cognitive, psychological status and determination of a number of biomarkers.

Introduction. Biological age is an indicator of the functional integrity of the body. It is a more accurate predictor of health status and mortality compared to chronological age, and also has the potential to evaluate the effectiveness of geroprotective interventions. Biological age is calculated using biomarkers of aging, which include various biochemical, genetic, phenotypic and functional characteristics of the body. To measure biological age, statistical analysis methods and neural networks with deep machine learning are used. The resulting formulas and calculation methods are called biological age calculators or “ageing clocks”. Purpose. Our study was aimed to examine existing biological age calculators and describe the potential difficulties of translating them into clinical practice.

Materials and methods. A literature review was performed on the PubMed platform spanning the last 5 years. The search was performed using the keywords “aging clocks, ageing clock, age clock, biological age” for the period from 2018 to 2023. Reviews, systematic reviews, and meta-analyses were included in the search query. A total of 136 articles matching the search query were found.

Research results. The results derived from the literature analysised, demonstrated that the most accurate currently existing “ageing clock” is the second generation epigenetic clock. They estimate both biological age and all-cause mortality (DNAm PhenoAge, DNAm GrimAge), as well as take into account the potential aging phenotype. The data required for these epigenetic biological age calculators includes not only DNA methylation information, but also additional information: some clinical indicators (PhenoAge, GrimAge), as well as a smoking index (GrimAge).

However, the lack of availability of DNA methylation assessment may cause difficulties when translating the epigenetic “aging clock” into clinical practice. From this perspective, the assessment of biological age using spectrometry and chromatography on proteome or metabolome data, as well as the analysis of fecal microbiota associated with human biological age, might be more viable for routine practice.

At the same time, the existing “ageing clocks” do not allow an objective assessment of biological age, since they either consider a limited amount of data (such as Galkin’s deep microbiotic clock), or while it is known that different types of cells have different rates of aging, analyze data from a very large undifferentiated array of biomaterial (like Howarth's multi-tissue epigenetic clock or Manuela Rist's metabolomic clock based on blood and urine data). Finally, it is not entirely clear which exact mechanisms of aging underlie the data obtained on biological age; therefore, the points for geroprotective interventions remain unclear.

In our opinion, the limited predictive precision and challenging implementation process are the primary hindrances to translating the existing "aging clock" into clinical practice. Further studies are required to create a variety of highly specialized calculators that estimate the biological age of various body tissues and do not require complex invasive methods of collecting biomaterials, and a machine model trained to analyze a large array of data to create a more accurate integrative indicator in the form of the biological age of an individual.

Conclusion. The existing “aging clock” assesses the functional integrity of the body and predicts outcomes. However, the low accuracy and low availability of complex information processing methods currently limit the translation of this tool into clinical practice and require improvement of existing models of biological age calculators.

The aim of this study is to create an "aging clock" that accounts for novel allelic polymorphisms in full-genome sequencing results to determine biological age.

The .vcf files of 21 samples from a study investigating the role of individual genomic variants of brain morphogenesis factors in the development of cognitive impairment were used to examine the data structure. Full genome sequencing (GWAS) results in .vcf format will be used as raw data from our own study. Correlation analysis and machine learning methods will be applied to analyze the data. The following algorithm for data processing is proposed: preprocessing of raw data, comparison of found polymorphisms with known polymorphisms, establishment of correlation between found polymorphisms and known age-associated diseases, assessment of statistical significance of found new polymorphisms with age-associated parameters (using trained models), model selection, and "clock" validation.

In the process of algorithm development, the structure of .vcf files was studied in order to automate the search for new allelic polymorphisms in genes with known involvement in the development of age-associated diseases. Analysis of fullexome sequencing results from 21 samples identified several genomic variants (rs6265, rs4760, rs4758443, etc.) associated with impaired brain development and the occurrence of cognitive impairment and age-associated diseases according to the literature. Preliminary results of the analysis demonstrate that the proposed bioinformatics data processing method can potentially be used to estimate the biological age of the study sample; however, the small sample size does not allow us to establish the accuracy of the proposed analysis method. For this reason, an analysis of 5000 additional samples is planned to optimize the proposed "aging clock" algorithms and evaluate their accuracy.

Analysis of a larger sample of biological samples from patients with ageassociated diseases will make it possible to identify new allelic polymorphisms, which will further improve the accuracy of the "aging clock".

Relevance. Atherosclerotic involvement of the carotid arteries accounts for 17-20% of all lesions among the total number of lesions in all branches of the aorta. It is the main cause of ischemic strokes (30-52% of cases). Carotid endarterectomy is one of the radical methods for treating and preventing this complication, as there is currently no other sufficiently effective pharmacological treatment.

Aim to investigate the immediate outcomes of surgical treatment, assess the safety and rationale of using regional anesthesia in performing carotid endarterectomy in older patients (aged 60 and above).

Materials and methods. The study included 193 patients with brachiocephalic artery pathology who were hospitalized in the Vascular Surgery Department of the War Veterans Hospital No. 2 in Moscow from March 2021 to December 2022: 116 (60.1%) males, 77 (39.9%) females, aged 60 to 96 years, with a mean age of 78.5 years. The cause of carotid artery involvement was atherosclerosis and atherosclerosis combined with pathological tortuosity of the vessel.

When determining the indications for surgery on the carotid artery, the clinical picture, degree of stenosis (70% or more), characteristics of the atherosclerotic plaque, and linear flow velocity (LFV) on the pathologically tortuous vessel were taken into account.

All patients underwent preoperative consultation with a geriatrician for comprehensive geriatric assessment (CGA) and medication review. They also underwent CT angiography of the brachiocephalic arteries with evaluation of the Willis Circle, native CT of the brain, esophagogastroduodenoscopy, echocardiography, carotid ultrasound, and consultations with a cardiologist, neurologist, and medical psychologist. General anesthesia was used in 8 cases (3.9%) and regional anesthesia in 185 cases (96.1%) during the surgical intervention. Regional anesthesia involved a combination of conduction and local infiltrative anesthesia, including deep (cervical and/or anterior approach) and superficial cervical plexus block and infiltration of soft tissues in the area of the mandibular angle.

Results. The mortality rate was 2.0% (4 patients), with one death due to recurrent stroke and three deaths due to acute myocardial infarction. There were 3 cases of stroke (1.5%): one patient died, one underwent thrombectomy within 2 hours with regression of neurological symptoms and full recovery, and one patient had neurological symptoms resolved one month after the stroke. Two patients (1.0%) required repeat surgery due to bleeding. No wound-related issues were noted.

Conclusion. The implementation of geriatric scales in surgical practice allows for a more careful selection of patients for surgical treatment based on their physical and cognitive status rather than solely on age, which helps minimize the risks of complications in the perioperative and postoperative periods. The use of regional anesthesia with simultaneous assessment of tolerance to cerebral ischemia allows for reliable monitoring of cerebral protection during temporary occlusion of the carotid arteries, enabling timely measures for preventing intraoperative ischemic injuries, such as the use of temporary bypass shunts. The safety of the technique allows its application in older patients with comorbidities and high anesthesiological risk. Currently, general anesthesia remains the main choice for analgesia during carotid artery surgeries. Regional anesthesia is still a subject of discussion in carotid artery surgeries. Studies and articles highlight both the advantages and disadvantages of each analgesic method. In our daily practice, regional anesthesia accounts for more than 95% of the total analgesic approach in carotid endarterectomy.

Relevance. The geriatric service at the Russian Gerontology Research and Clinical Centre of Pirogov Russian National Research Medical University places great emphasis on telehealth consultations conducted by their specialists, as it is a crucial aspect of maintaining active longevity.

Aim. In this paper, we aim to analyze the structure of telehealth consultations conducted in geriatrics.

Materials and methods. The annual reports of the Chief Geriatrician of the Voronezh region.

Results. Throughout 2020 and 2021, the National Medical Research Center for Geriatrics in the Voronezh region held 14 and 30 telehealth consultations, respectively, with experts. In 2022, the number of telehealth consultations reached 48, the Voronezh region took 7th place among the regions of the Russian Federation. Over the three quarters of 2023, 56 telehealth consultations were carried out in the Voronezh region. Telehealth consultations are carried out according to the schedule approved by the Department of Health of the Voronezh Region. Geriatricians in Voronezh and the Voronezh region take an active part in preparing patients and providing the required documents. Experts of the Russian Gerontology Research and Clinical Centre of Pirogov Russian National Research Medical University provide consultation protocols with detailed recommendations for the examination and treatment of older patients. Analysis of the performed telehealth consultations showed that patients suffering from frailty of mild and moderate severity, suffering from cardiovascular and endocrine diseases predominate. Improving the effectiveness of treatment for these patients will improve the autonomy of these patients and, therefore, improve their quality of life.

Conclusions. Use of the regional segment of the Unified State Health Information System when conducting telehealth consultations in geriatrics (profile “Doctor - Doctor”) allows to increase the effectiveness of older patients treatment.

The male aging is accompanied not only by decrease in testosterone synthesis, but also by the activation of a number of enzymes, an increase in the conversion of some hormones to others, a change in the number of hormone-producing cells and receptors, a violation of the sensitivity of receptors and the balance of hormones. Taking into account the pathophysiological processes with age, when body composition changes, muscle mass decreases and adipose tissue increases, as well as the global increase in the number of men with excess body weight due to adipose tissue, there is an increase in the activity of the aromatase enzyme, which converts testosterone into estradiol. Over time, estradiol suppresses the synthesis of gonadotropins, thereby suppressing testosterone synthesis. Consequently, this results in a decline in both physical and sexual activity, as well as a progressive accumulation of adipose tissue, which triggers aromatase and raises estradiol levels. In other words, a vicious circle is formed. In addition to the decrease in the number of testosteronesecreting Leydig cells, both the number and sensitivity of androgen receptors decrease.

To successfully extend the longevity of men and ensure their well-being, it is essential to take into account the individual endocrine changes that come with aging.

Relevance. By 2030, the Russian Federation aims to increase the life expectancy at birth to 78 years as part of its national development plan [1]. This target value cannot be achieved without a reduction in mortality rates among older demographics and an increase in the life expectancy of the aging population.

Aim. To identify reserves for reducing mortality among older population in Russia and the contribution of older age groups to the increase in life expectancy at birth.

Materials and methods. Data from the Federal State Statistics Service (FSSS) on causes of death with population distribution by gender, five-year age groups, and brief nomenclature of death causes for 2022 were used for mortality analysis; data on the average annual population by gender and five-year age groups for 2022; and data from the average forecast variant of FSSS on population size by age groups up to 2030. Data from the Human Mortality Database [2] and agespecific mortality rates by causes of death from the WHO mortality database [3] were also used. The contribution of changes in mortality by age groups and causes of death to the increase in life expectancy was calculated using the decomposition method [4]. The forecast contribution of causes of death to the increase in life expectancy in older population was calculated taking into account the mortality structure by causes of death in 2022 (excluding malignant neoplasms and the Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified class).

Results. Since 2005, Russia has seen a steady increase in life expectancy, interrupted in 2020–2021. COVID-19 pandemic. For the period from 2005 to 2019. Life expectancy for men at birth increased by 9.3 years (from 58.9 to 68.2 years), while the decrease in mortality among men in age groups over 60 years accounted for 21% of this increase. Life expectancy of women at birth for 2005–2019. increased by 5.7 years, the contribution of the reduction in mortality over the age of 60 years was 48%.

Most of the decline in mortality in old age was determined by a reduction in mortality from diseases of the circulatory system. At the same time, there was an increase in mortality from symptoms, signs and abnormalities (ICD-10 class, including the cause of death old age and other codes for undetermined causes), and from other causes of death, incl. diseases of the nervous and endocrine system.

The contribution of the older population to life expectancy at birth increases as this indicator increases. Thus, in the period from 2005 to 2011. The decline in mortality among people aged 60 years and over accounted for 29% of the total increase in life expectancy at birth, from 2011 to 2019. Тhe contribution of reducing mortality in old age increased to 36%. According to the forecast until 2030, when life expectancy at birth reaches 78 years, by 2030 39% of the total growth in the indicator will be provided by age groups over 60 years of age, including almost 30% for men and more than 50% for women.

The forecast for 2030 shows that almost half of the potential increase in life expectancy at age 60 is linked to illnesses of the circulatory system, specifically coronary heart disease and various cerebrovascular events.

According to our estimates, the second most important contribution to life expectancy growth reserves is made by the class Symptoms, Signs and Deviations from the norm (uncertain causes of death, including old age). Age-specific mortality rates from this class of causes increase sharply after age 80 years. Using cause-of-death codes from this class underestimates mortality from other causes of death, including diseases of the circulatory system, neoplasms and other diseases [5] and requires improved quality of coding and selection of the original cause of death when completing medical death certificates.

The next leading causes of death are malignant tumours and COVID-19 (about 9%). Neoplasms are in second place in the structure of mortality in older population after CSD, however, the estimated contribution of changes in cancer mortality to the increase in life expectancy is significantly lower than both diseases of the circulatory system and the class of Symptoms, signs and abnormalities. It was previously shown that in Russia, a decrease in mortality from neoplasms is to a lesser extent a reserve for increasing life expectancy compared to diseases of the circulatory system and external causes [6]. Evidence from other countries between 1970 and 2018 supports a decrease of less than 25% in the standardized mortality rate from neoplasms in the EU-15 countries, while from diseases of the circulatory system it was more than 70% [7].

The remaining reserves aimed at extending the life expectancy in older population are distributed among conditions such as diabetes, nervous system diseases, respiratory and digestive disorders, and external causes leading to mortality.

Conclusion: With increasing life expectancy and aging population, the focus shifts to decreasing mortality rates among older adults, in light of the rising life expectancy at birth. Thus, it is crucial to implement targeted strategies in order to decrease mortality rates among individuals aged 60 and above. In order to increase life expectancy, priority areas in health care planning should be diseases of the circulatory system, which determine about half of the reduction in mortality in older age. Enhancing the quality of statistics on causes of death within this age demographic is crucial, as the common use of vague causes of death prevents a detailed examination of mortality in old age and complicates the creation of targeted approaches to reduce it.

Advanced glycation end products (AGEs/AGE) are represented by a large heterogeneous family of sugar-modified proteins, lipids, and nucleic acids associated with numerous age-related diseases including diabetes mellitus, atherosclerosis, chronic obstructive pulmonary disease, Alzheimer's disease, oncogenesis, etc [1-5].

At the Nutrition Research Institute of the Republic of Korea, specialised probiotics were selected and developed from 700 types of lactic acid bacteria derived from traditional Korean foods: sauerkraut (KimChi) and soy sauce; with detection of efficacy in the degradation of AGE foods. Strains were identified and analysed by 16S sequencing, biochemical analysis (API 50CHB) was used, enzymatic properties were studied (API Zym), and utilized food ingredients (DB) were analysed. Subsequently, selection of suitable strains was carried out. As a result, an active strain of Lactococcus lactis KF140 capable of significantly degrading CPG was obtained and patented (Park Ho Young et al., 2018).

In a double-blind randomised study on healthy volunteers, this probiotic strain was shown to reduce blood levels of carboxymethyllysine, one of the most potent pro-oxidants of AGEs, by 90% (P < 0.001) after 26 days of supplementation with a Parmesan cheese loading diet. The strain was also found to reduce ALT (P < 0.001), LDL-cholesterol (P < 0.01), and glycated haemoglobin levels from 5.0% to 4.7% and AST levels from 19.1 to 15.4 U/L, respectively. One of the mechanisms of the strain's effect on carboxymethyllysine levels was related to the activity of the enzyme β-lactosidase, as shown in in vitro experiments. In addition, the administration of KF-140 altered the abundance of 11 intestinal microbes at the species level. This probiotic strain is included in commercial dietary supplements. Thus, Lactococcus lactis strain KF140, along with correction of the microbiota, is considered as a promising substance to reduce the accumulation of AGE-products and, accordingly, as one of the factors in preventing the development of age-associated diseases and oxidative stress in chronic inflammation.

Relevance. The development of ischemic stroke (IS) is obligately accompanied by activation of the stress-releasing system. Predominant activation of hypothalamic-pituitary-adrenal axis is associated with a worse IS acute period prognosis. At the same time, the question of the stress-releasing system role in the brain neurons death regulation in IS remains unexplored.

Purpose to study the effect of peripheral blood cortisol concentration on the regulation of apoptosis of cerebral cortex neurons in the acute period of ischemic stroke.

Materials and methods. A prospective clinical and pathomorphological study was carried out. The study included 9 left middle cerebral artery who were admitted to the hospital and died in the acute period of IS in the absence of infectious complications, allergic reactions, oncological diseases, and who did not undergo thrombolysis. Examined the cerebral cortex. On sections, an indirect immunoperoxidase immunohistochemical method revealed neuron specific enolase (NSE), protein p53 (p53), caspase 3, caspase 8, Fas-receptor (CD95), Fas-ligand (CD178), Fas-apoptosis inhibitory molecule 2 (FAIM2). A total of 567 visual fields were processed for the group of patients after IS and 63 visual fields for the control group (3 people). Before the onset of death in the blood, the concentrations of sFas, sFasL, cortisol, adrenocorticotropic hormone, epinephrine, noradrenaline were measured by enzyme immunoassay (the control group consisted of 28 people).

Results. An increase in the proportion of neurons expressing proteins responsible for apoptosis was detected in the cerebral cortex compared to the control group; decrease in the proportion of p53, casp8, casp3-positive cells with distance from the ischemic core.

The proportion of neurons expressing membrane forms of Fas receptors in the 1st zone of the study was the largest, and in the 2nd and 3rd zones it significantly decreased. Expression of membrane Fas ligands was detected on 63.6 (58.3;70)% of NSE positive cells in the 1st zone, which significantly (p < 0.01) differed from control samples (75.5 (66.7;81.5 )%) to a lesser extent, while zones 2 and 3 were characterized by a significant increase in the proportion of neuronal cells expressing FasL, respectively, to 78.1 (71.4;85.7)% (p < 0.05) and 89.1 (81 .4;93)% (р < 0.01). In the 3rd zone, a decrease in the proportion of Fas- and casp8-positive neurons was revealed with an increase in the proportion of FasL-positive non-neuronal cells (r = -0.160, p < 0.05 and r = -0.211, p < 0.01, respectively). The proportion of FAIM2 positive neurons in the 2nd zone was 73 (67.9;78.9)% and did not differ significantly from the indicators of samples in the control group (72.4 (66.1;76.8)%). In the remaining study areas, the differences from the control were significant (p < 0.01), and the values of the indicators were lower. Significant correlations were revealed between the proportion of caspase 3-positive neurons and the concentration of cortisol in peripheral blood in zones 2 (r = 0.263, p < 0.01) and 3 (r = 0.383, p < 0.01). In zone 2, significant negative correlations were noted with the concentrations of sFas (r = -0.177, p < 0.05) and sFasL (r = -0.164, p < 0.05), in zone 3 — significant positive correlations with the ratio of concentrations of sFasL and sFas (r = 0.240, р < 0.01). The proportion of Fas-positive neurons in the cerebral cortex significantly correlated with the concentration of the soluble form of this molecule (for the 1st zone - r = 0.222, for the 2nd zone - r = 0.438, for the 3rd zone - r = 0.289, р < 0.01) and the ratio of concentrations of sFasL and sFas (for zones 1 and 2, respectively: r = 0.231, r = 0.266 and r = 0.281, p < 0.01) in peripheral blood.

Conclusions: The cortisol concentration in peripheral blood has a significant effect on the cerebral cortex neurons apoptosis regulation in the acute IS period.

Relevance. Understanding the biological mechanisms of aging is necessary to prevent and slow down the development of age-associated diseases. One of the leading causes of aging considered to be the accumulation of so-called senescent, or aging, cells (SC). Cellular aging is necessary for tissue renewal and regeneration, but excessive accumulation of SC leads to the activation of chronic aseptic inflammation, tissue dysfunction and development of age-associated diseases. Currently, approaches to selective elimination of SCs, as well as control of their activity and reversion of the senescent state are being actively developed. The assessment of stem cell involvement in aging and disease development requires the use of dependable and relevant biomarkers. A commonly used biomarker to indicate a cessation in cell growth is the expression of cell cycle inhibitors (for example, p16/INK4a) since the arrest of proliferation is one of the main attributable features of SC. However, evaluation of this marker is difficult inclinical practice. Typically, the stiffness ofthe vascular wall, some hemodynamic and biochemical parameters, as well as the content of certain cytokines and growth factors in the blood are determined as markers of age-associated diseases. In this work, we aimed to study the relationship between established clinical systemic biomarkers of aging and development of age-associated diseases and biomarkers of KS at the tissue and cellular levels.

The aim of the study is to establish the associations between various biomarkers of SC accumulation at the cellular, tissue and system levels.

Materials and methods. Study included 38 patients aged 65 to 85 years. In all patients, traditional risk factors for cardiovascular diseases, arterial wall stiffness were assessed, and samples were obtained (peripheral blood, skin, subcutaneous fat), from which various types of cells were then isolated (mononuclear blood cells (MBC), fibroblasts (FB) and mesenchymal stromal cells (MSCs), and also histological analysis of biopsy specimens to evaluate various MC markers was performed.

Results. In the obtained samples, various indicators of the accumulation of senescent cells were determined, and the relationships between the rigidity of the vascular wall, traditional risk factors for CVD, biomarkers of inflammation and the accumulation of senescent cells in tissues and cell populations were analyzed. Using correlation analysis, a strong significant association was confirmed between the key biomarker of KS — the level of p16 expression in tissues — and age (r = 0.6, p < 0.001), which corresponds to literature data [2]. At the organismal level, its relationship with the pulse wave velocity (r = 0.394, p = 0.015), in the systemic circulation — with the level of VCAM-1 (r = 0.312, p = 0.006) and with the level of p16 mRNA in the MNC (r = 0.380, p = 0.046). Statistically significant correlations were identified with the proliferation rates of PB and MSCs in culture and the acquisition of the agingassociated secretory phenotype (SASP) by cells: thus, level of p16 significantly correlated with the level of IL-6 (strong relationship) and MCP-1 (weak relationship) in cell secretome. The results of multivariate linear regression analysis confirmed that, regardless of age, p16 expression is associated with the proliferation of isolated cells and IL-6 in SASP. Using computer modeling, after normalizing the characteristics, a formula was determined that allows one to predict the level of p16 expression in tissues, relying only on non-invasively determined indicators.

Conclusion. Thus, the association between clinical parameters reflecting vascular aging and biomarkers of SC accumulation in tissues and in cells isolated from these tissues into culture has been demonstrated. The possibilities of minimally invasive determination of indicators of accumulation of senescent cells in patients over 65 years of age have also been determined, which opens up new opportunities for monitoring the effectiveness of senolytic therapy.

Relevance. It is a widely recognized fact that variations in the genes responsible for drug transportation and metabolism can impact their pharmacokinetic properties. ABCB1 gene polymorphisms, in particular, have been linked to alterations in drug distribution and the onset of negative side effects. The results of studies regarding the effect of ABCB1 genetic variations on the drug response to rivaroxaban are contradictory, which was the subject of our study.

Aim. This study is aimed to evaluate the effect of ABCB1 gene polymorphism (rs1045642 and rs4148738) on the pharmacokinetics of rivaroxaban in patients 80 years of age and older with non-valvular AF.

Materials and methods. We examined 128 patients over 80 (mean age 87.5 years [83–90 years]) with non-valvular atrial fibrillation (AF). Every patient underwent genotyping of the rs1045642 and rs4148738 polymorphisms of the ABCB1 gene, determination of the minimum equilibrium concentration of rivaroxaban (Cmin, ss), prothrombin time (PT) in blood plasma and analysis of medical documentation for the presence of minimal clinically significant bleeding (clinically relevant nonmajor (CRNM) bleeding). Additionally, the results were assessed taking into account the range of the therapeutic window for rivaroxaban Cmin,ss (6–87 ng/ml), and standardization of the minimum equilibrium concentration of rivaroxaban per daily drug dose (Cmin,ss / D) was carried out.

Results. In SS carriers compared with patients carrying CT and TT for rs1045642 and rs4148738 of the ABCB1 gene, there were no significant differences in the values of Cmin,ss of rivaroxaban, Cmin,ss/D of rivaroxaban and the number of patients in whom Cmin,ss exceeded the range of 87 ng/ml (p > 0.05). The PT level in CC carriers compared to patients carrying the CT genotype rs1045642 (ABCB1) did not differ significantly, while in TT carriers the PT level was higher compared to carriers of the CC genotype rs1045642 (ABCB1): Me 14.2 [13.0– 16.1] sec versus Me 13.3 [12.4–14.5] sec (p = 0.049). The level of PT in carriers of CC compared with carriers of ST and TT for rs4148738 of the ABCB1 gene did not differ significantly. In TT carriers, CRNM bleeding was significantly more common compared to CC carriers for rs1045642 of the ABCB1 gene (29.3% versus 4.5%, p = 0.021). In carriers of TT, CRNM bleeding was significantly more common compared to carriers of CC (39.3% vs. 8.1%, p = 0.008) and CT of the ABCB1 gene mutated at rs4148738 (39.3% vs. 14.3%, p = 0.002).

Conclusions. Our data did not show the effect of ABCB1 gene polymorphism (rs1045642 and rs4148738) on the pharmacokinetics of rivarxaban in patients 80 years and over with non-valvular AF in routine clinical practice. However, in TT carriers, CRNM bleeding was significantly more common in comparison with CC at rs1045642 of the ABCB1 gene and in comparison with CT and CC at rs4148738 of the ABCB1 gene, which requires a more profound study of genetics contribution to the pharmacological response of rivaroxaban.

Relevance. Aging of the human body is accompanied by gradual reduction in the reserve of adaptive capacity and fragility, which represents an increased ulnerability to the impact of various factors. Sarcopenia refers to the fragility criteria associated with age-related degenerative changes in skeletal muscles, including gradual loss of muscle mass and decreased strength. It is considered one of the top five risk factors for severe illnesses and high mortality rates in people over 65.

Aim. the purpose of this study was to determine the incidence of probable sarcopenia as a marker of physiological aging.

Materials and Methods.Study groups were divided into youngest-old individuals (45–59 years, n = 482), middle-old individuals (60–74 years, n = 462), oldestold individuals (75 years and older, n = 291). All citizens who signed informed consent were examined according to the protocol of the European consensus on sarcopenia (EWGSOP2) with determination of walking speed, muscle strength by handgrip strength using a dynamometer and body composition assessment with determination of skeletal muscle index (SMI, kg/m2) using bioelectrical impedance analysis (BIA) (InBody, Korea), filling out the SarQoL questionnaire. According to the EWGSOP2 consensus, the term "probable sarcopenia" refers to a decrease in muscle strength, which is currently the most reliable indicator of muscle function. Inclusion criteria: compliance with the age criterion, absence of acute infectious diseases, exacerbation of chronic non-infectious diseases, absence of psychiatric diseases. Statistical processing was performed using the computer programme STATISTICA 10.0.

Results. The mean age in the 45–59 years group was 50.6 ± 5.5 years, with 15.8% men (n = 76) and 84.2% women (n = 406). The mean age in the elderly group was 67.1 ± 3.9 years, the gender composition was predominantly represented by women 80.3% (n = 371), the proportion of men was 19.7% (n = 91). In the group over 75 years old, the mean age was determined to be 79.2 ± 4.3 years, with 79% (n = 270) women and 21% (n = 61) men. The frequency of probable sarcopenia in 6.6% of middle-aged subjects (n = 32) and 17.1% of elderly subjects (n = 79) was found to be less than the threshold value (χ2, p = 0.001). The highest frequency of probable sarcopenia was determined in the group of elderly subjects — in 41,2% of subjects (n = 120), (χ2, p = 0,001). Thus, a significant acceleration of muscle mass loss is observed after 60 years of age and is an important characteristic of physiological aging (Fig.1).

Conclusions. The rapidly shifting age structure of the population will impact the frequency and occurrence of ageing-related conditions, such as sarcopenia. Our top priority should be to enhance the length and quality of life. The introduction of preventive measures is advisable at the stage of probable sarcopenia in order to preserve the ability to social functioning and self-care among the older and oldest-old.

Relevance. The coronavirus pandemic has had the most painful impact on older patients, including those living in social homes. Residents of closed-type care facilities are more at risk of contracting novel coronavirus infection (COVID-19) due to overcrowding and frequent contact with staff. They often experience a loss of support, there is forced social isolation amid anti-epidemic measures, and there is a decrease in cognitive stimulation. All these factors cause emotional disorders of the anxiety-depressive spectrum, and accelerate the decline of cognitive functions. Patients with acquired dementia are more sensitive to COVID­-19, since its risk factors are identical to the risk factors for vascular dementia (cardiovascular diseases, obesity, diabetes mellitus); and, in addition, mental disorders themselves prevent patients from complying with preventive measures. The study of cognitive and non­cognitive impairments in people after COVID­-19 is associated with the obvious need for their better psychological adaptation to cognitive dysfunction in vascular dementia, improving quality of life (QOL) and functional independence.

Aim: to study the dependence of quality of life on cognitive and emotional disorders in patients with mild vascular dementia following COVID-19. Materials and methods. We studied 132 residents (67 men, 65 women; mean age 73.05±3.48 years) from the “Severnoye Izmailovo” nursing home, the Department of Labor and Social Protection of the Population of Moscow, with mild vascular dementia (according to ICD­10 diagnostic criteria). We identified two comparison groups: subjects with a duration of clinical onset of COVID-19 confirmed by a positive PCR test, 6 months +/– 1 month, with an outcome of recovery confirmed by a negative PCR test (n = 65; 33 men, 32 women), and non-survivors of COVID­-19 (hospital control group) (n = 67; 34 men, 33 women). The gender and age composition of the compared groups was homogeneous (p > 0.05). To study the quality of life of patients, we used the Quality of LifeAlzheimer's Disease (QoL-AD) questionnaire, which includes the study of selfassessment of quality of life (QoL-AD-SR (self-rating)) and proxy rating of quality of life (indirect assessment QoL by caregivers (QoL-AD-PR (proxy rating)) This questionnaire assessed the following areas of QoL: physical health, strength, mood, living conditions, memory, family, marriage (relationships with loved ones), friends, general self-esteem , ability to do housework, ability to have fun, money, life in general. To evaluate the current emotional state, the Cornell Scale for Depression in Dementia (SCDD; probable depression was diagnosed when a score exceeded 10) was used. In addition, to estimatete cognitive status of patients, we used the Montreal Cognitive Assessment (MoCA), which assesses various cognitive areas: attention and concentration, executive functions, memory, language, visual constructive skills, abstract thinking, counting and orientation. Cognitive dysfunction was recorded when the result was less than 26 points on this scale. Statistical processing of the study data was carried out using the Statistica 6.0 package.

Results and discussion. It was found that COVID-19 aggravated cognitive deficits in older people with LSD (MoCA 20.80 ± 0.59 / 21.40 ± 0.78 points; p<0.05) in the absence of depression (SCDD 1.52 ± 0 .50 / 1.52 ± 0.84 points in the group of survivors of COVID-­19 / hospital control group, respectively; p > 0.05). The results obtained indicated direct damage to the brain contributed by COVID­19 have led to increased existing cognitive impairment in persons with vascular dementia. Self-assessment of quality of life (QoL-AD-SR) in persons with mild vascular dementia was 30.32 ± 2.89 points. In patients who recovered from COVID­19 and 29.76 ± 4.08 b. in those who were not ill, and the proxy rating of quality of life (QoL-AD-PR) was 30.26 ± 2.08 points and 29.22 ± 3.67 b. in the study groups, respectively, without statistical differences between them (p > 0.05). Such results were explained by the fact that in patients living in psychoneurological boarding schools, “pre-Covid” cognitive disorders and somatogenic asthenia “mask” the progressive deterioration of QoL.

In survivors of COVID-19, a correlation was found between the proxy rating of QoL and the severity of cognitive dysfunction according to MoCA (R = — 0.28); and in the hospital control group — between the proxy rating of QoL and the severity of depressive symptoms (R = — 0.33). No other significant correlations were found in the study groups between self-assessment of quality of life (QoL-AD-SR) and the severity of cognitive and emotional disorders.

In other words, there was a correlation between progressive cognitive impairment and QoL in older individuals with LSD following COVID-19. They showed symptoms of irritable weakness as part of the asthenic variant of the psychoorganic syndrome; There was a worsening of labile cerebrastia due to an increase in cognitive disorders with a decrease in the proxy assessment of QoL, which caused intrapersonal disadaptation (“capitulation” to the disease, “withdrawal”) and required individual forms of psychotherapeutic work (cognitive training).

In addition, a correlation was found between the severity of depressive symptoms and quality of life in older individuals with mild vascular dementia without comorbidity with previous COVID-19. This cohort of patients was distinguished by an acute experience of feelings of loneliness and worthlessness, a pessimistic worldview, vulnerability, concern about unfavorable assessments of others (patients were afraid of pity and being a burden, which led to instability of mood in interpersonal contacts), which indicated their interpersonal maladaptation, requiring group forms of psychotherapeutic correction of negative emotional experiences.

Conclusions. In older patients — residents of psychoneurological boarding schools, suffering from mild vascular dementia and having undergone COVID-19, there is a significant worsening of only cognitive deficit, without depressive manifestations. COVID-19 worsens the proxy assessment of their QOL due to worsening cognitive deficits. In “covid-free” patients, the proxy rating of QoL has a correlation with the severity of emotional disturbances. The identified patterns can contribute to the optimization of personalized models of medical and psychological rehabilitation of older patients with mild vascular dementia living in psychoneurological boarding schools. To improve psychological adaptation to cognitive deficit and improve quality of life in this cohort of patients, individual cognitive training is advisable among those who have suffered from mild vascular dementia, and group psychotherapeutic correction of negative emotional experiences among those who have not suffered from COVID-19.

According to the research results from Semashko National Research University, the development of age-related diseases is greatly influenced by the interaction of chronic conditions. The presence of three or more diseases can trigger a chain reaction in comorbidity, ultimately leading to non-viability of the organism due to high morbidity rate (comorbidity critical rate — CCR). CCR value depends on gender (6 for men; 8 for women), age (the highest value of CCR in men at 65 years old, in women at the age of 85) and the severity of concomitant diseases, which is determined by the influence of diseases. It is proposed to use the calculated CCR value as a comparative characteristic of the public health in regions.

The demographic shift towards an aging population and the subsequent rise in retirement age are driving the upward trend of doctors in older age brackets. The prevalence of comorbidity and cognitive decline among this demographic calls for effective strategies to minimize the risk of geriatric conditions as well as maintain required professional competence.

Semashko National Research Institute of Public Health has introduced a comprehensive technology that helps prolong the medical practice for older doctors. Its main goal is to optimize their work and stimulate their professional competence. Implementation plan is provided.

The proportion of individuals affected by dementia worldwide currently stands at over one percent and is anticipated to double within the next 20 years. Meanwhile, the accuracy of diagnosing the prevalent type of dementia, Alzheimer's disease, remains below 10%. The absence of uniform diagnostic criteria for each type of dementia is a major factor contributing to misdiagnosis. Poor detection results, coupled with the lack of profound treatment methods, places dementia among the main threats to public health. The research team from Semashko National Research Institute successfully structured and digitized diagnostic criteria for the main forms of dementia, resulting in the creation of MIS "Dementia" basing on the 1C web platform (MIS — certificate No. 2022664724 dated July 22, 2022), intended for diagnosis, out-of-office monitoring and treatment of 44 forms diseases. After the clinical trials are finished and the MIS is approved, it will be implemented in the organization of memory impairment clinics.