Osteoporosis is a serious public health concern worldwide, characterized by decreased bone mineral density (BMD) and impaired microarchitecture of bone tissue, leading to an increased incidence of low-trauma fractures. Osteoporosis typically affects older adults, but it can also occur at younger ages due to impaired absorption of calcium and vitamin D in various gastrointestinal (GI) diseases. NAFLD is a risk factor for decreased bone mineral density (BMD). New data on the pathophysiological changes in bone tissue in NAFLD are presented: release of inflammatory cytokines, decreased secretion of molecules directly affecting bone (strengthening bone) from the liver affected by NAFLD, impaired vitamin D metabolism, and impaired intestinal microbiota. NAFLD is a risk factor for decreased BMD.

Further research is needed to confirm the physiological significance of NAFLD with regard to the risk of osteoporotic bone fractures. Mandatory osteoporosis screening and bone health monitoring in patients with NAFLD may be possible in future NAFLD management strategies and guidelines.

BACKGROUND. Healthy, good quality sleep is one of the necessary conditions for achieving longevity and enhancing survival. Numerous general population studies revealed a relationship between some sleep-related habits and mortality, but the results of similar studies conducted in older participants are not so unambiguous.

AIM. To study the impact of sleep-related habits on the 5-year survival rate in participants aged ≥75 years.

MATERIALS AND METHODS. The study included 223 participants (24% men) aged 75–98 years (median age: 87 years) who lived in Moscow and the Moscow region and were receiving routine inpatient care at the Russian Gerontology Clinical Research Center in 2011–2013. At admission, patients were surveyed using a specially developed questionnaire in order to assess social and behavioral factors such as lifestyle, habits, diet, and physical activity. The questionnaire included the following sleep-related items: 1) bedtime; 2) wake-up time; 3) nighttime sleep duration; 4) daytime napping. After discharge, patients were under follow-up for 5 years. Cases of all-cause mortality were registered.

RESULTS. During 5 years of follow-up (median: 3.63 years), 88 (39.5%) people died. Accordingly, the 5-year survival rate was 60.5%, and the mean survival time was 4.44 [95% confidence interval (CI) 4.19–4.71] years. The study demonstrated that the most of the participants went to bed at 10–12 p.m. (65%), woke up at 6–8 a.m. (58%) and had a daytime napping (61%), and 68% of the participants had the duration of nighttime sleep within 7–9 h. Univariate regression analysis showed that late (after midnight) bedtime, waking up after 8 a.m., and long (≥10 h) nighttime sleep were associated with a 1.7–2.1-fold increase in the risk of death over the next 5 years. On the contrary, early (before midnight) bedtime, waking up between 4–8 a.m., and nighttime sleep for 5–9 h were associated with a 43–52% decrease in the risk of death over this period. Daytime napping had no effect on the 5-year survival rate. Multivariate regression analysis demonstrated that age (hazard ratio [HR] 1.09; 95% CI 1.02–1.17; p = 0.019), early (before midnight) bedtime (HR 0.55; 95% CI 0.31–0.97; p = 0.040) and 5–9 h nighttime sleep duration (HR 0,44; 95% CI 0.26–0.76; p=0.003) were independent predictors of the 5-year survival rate.

CONCLUSION. In participants aged ≥75 years, who lived in Moscow and the Moscow region, early (before midnight) bedtime and medium (5–9 h) nighttime sleep duration are independent predictors for the 5-year survival rate and are associated with 45% and 56% reduction in the mortality risk, respectively, suggesting that a proper sleep may be a geroprotective factor.

BACKGROUND.One of the key indicators of immunosenescence is inflammatory aging (inflammaging), which is primarily attributed to the mechanisms of innate immunity. The assumed cause of inflammaging is chronic activation of patternrecognizing receptors of the innate immunity and their signaling pathways by endogenous and exogenous danger signals. The major role in this process is held by Toll-like receptors (TLR) and NOD-like receptors (NLR). Their activation triggers the implementation of effector mechanisms of innate immune defense; in the context of aging, this contributes to the development of a pro-inflammatory phenotype. Inflammaging can lead to normal aging and longevity, as well as to pathological aging and age-associated pathology. Currently, several receptor and effector components of the innate immune system have been examined in the context of aging and various age-related diseases. However, few studies have been conducted on the contribution of innate immunity components to normal aging; no analysis of specific mechanisms of innate immunity in various aging phenotypes has been conducted. AIM. To conduct a complex study of the innate immunity system (signaling receptor system, inflammasome complex components, cytokines) in elderly individuals and long-living individuals with various aging phenotypes.

MATERIALS AND METHODS. A total of 100 elderly individuals, 100 longliving individuals and a comparison group consisting of 50 young people were examined. Within the elderly and long-living groups, physiological and pathological aging phenotype subgroups were divided based on the Charlson Comorbidity Index, the Short Physical Performance Battery and the Mini-Mental State Examination. Peripheral blood was used as a biomaterial for the study. The expression levels of the pattern recognition receptor genes (TLR2, TLR4) and inflammasome complex genes (NLRP3, CASP1) in leukocytes were assessed by real-time polymerase chain reaction (RT-PCR). Surface expression of TLR on monocytes was determined by flow cytometry. The concentration of cytokines in the blood serum and in the mononuclear cell culture (MNC) of the study groups was measured by enzyme immunoassay. The obtained data were assessed using the Statistica 14 software package (StatSoft, Europe) and GraphPad Prizm (Prizm, USA).

RESULTS. Analysis of the age-related changes in expression of pattern recognition receptors TLR2, TLR4 at the transcriptional and protein levels revealed an increase in TLR2 expression and a decrease in TLR4 expression in the group of elderly and long-living individuals compared to the young participants. In the normal aging phenotype, an increase in TLR2 expression was recorded in both the elderly and long-living individuals. In the pathological aging phenotype, TLR2 hyperexpression was observed in elderly individuals, and TLR2 expression was decreased in long-living individuals. No significant differences in the expression of the TLR4 gene and protein were found in older participants depending on the aging phenotype. Assessing the expression of the inflammasome complex genes demonstrated an increase in the expression of the NLRP3 gene in the peripheral blood leukocytes of elderly and long-living individuals by 20 and 23 times, respectively, compared to young donors. In the pathological aging phenotype, both the elderly and the long-livers showed hyperexpression of the inflammasome complex genes (NLRP3, CASP1), which may be associated with the risk of developing ageassociated pathology. Since the main result of NLRP3 inflammasome activation is the processing of proinflammatory cytokines to a biologically active form, the level of IL-1β and IL-18 cytokines in the blood serum and in the MNC culture of the studied age groups was assessed. In long-living individuals, an increase in the levels of IL-1β and IL-18 in the blood serum was observed compared to the elderly and young donors. No differences in the content of IL-1β in the blood serum were found between the normal and pathological aging groups. An elevation in the levels of IL-1β in the MNC culture was observed during aging, with a more pronounced increase in the pathological aging phenotype.

CONCLUSIONS. Therefore, an increase in TLR2 gene expression may be regarded as a marker of normal aging, while hyperexpression of the NLRP3 gene and elevated levels of IL-1β in the MNC culture can be viewed as markers of pathological aging in elderly and long-living individuals. The identified markers of aging phenotypes will enable prevention of age-associated pathologies, thereby promoting healthy longevity.

BACKGROUND . Age-related changes occurring in the immune system during aging include dysregulation at the level of innate immunity and are described as inflammatory aging or “inflammaging.” Inflammatory aging presupposes lowlevel systemic inflammation, which is present even in clinically healthy people of older age groups and characterized by elevated blood levels of inflammatory mediators, including proinflammatory cytokines. Inflammatory reactions play a dual role: on the one hand, providing a protective reaction; on the other hand, mediating tissue damage with excess inflammation and its chronization. It is assumed that the nature of the aging process and the development of age-associated pathology are related to the balance of pro- and anti-inflammatory cytokines. AIM. To assess the levels of pro- and anti-inflammatory cytokines in long-living and elderly patients with various aging phenotypes.

MATERIALS AND METHODS. The study included 80 elderly participants (mean age: 81.8 years), 100 long-living participants (mean age: 92.2 years) and 50 young participants (mean age: 22.4 years) as a comparison group. The groups of elderly and long-living participants were divided into subgroups of the physiological and pathological phenotype of aging based on clinical data: the Charlson Comorbidity Index, the Short Physical Performance Battery and the MiniMental State Examination. The cytokine levels of patients in the study groups were assessed by enzyme immunoassay (ELISA) in blood serum, as well as in mononuclear cell culture (MNC) supernatants after 24 h of cultivation. The concentrations of the following cytokines were determined: IL-1β, IL-4, IL-6, IL-10, IL-18, TNFa, TGFß (Vector-Best kits, Russia and CloudClone Corp.,USA). The obtained data were assessed using the Statistica 14 software package (StatSoft, Europe) and GraphPad Prizm (Prizm, USA).

RESULTS. Assessment of serum cytokine levels showed that the concentration of both pro-inflammatory cytokines IL-6, TNFa, IL-1β, IL-18 and anti-inflammatory cytokines IL-10, TGFß was increased in the group of long-living participants. At the same time, an imbalance of cytokines was revealed in the elderly group, manifested by an increase in the concentration of IL-6 and a decrease in the level of IL-10 and TGFß. This imbalance of pro- and anti-inflammatory cytokines assumedly determines the transition from the phenotype of normal aging to a pathological variant characterized by the development of age-associated pathology. In addition, we revealed an increase in the level of IL-4 with a normal aging phenotype, which can be considered as a marker of this phenotype, and an increase in the levels of IL-6, TNFα as markers of the pathological phenotype of aging in elderly and long-living participants. The concentrations of cytokines IL-1, IL-4, IL-6, IL-10 and TNFα detected in blood serum are quite low. This leads to the need to make a diagnostic decision based on values at the lower detection limits of modern test systems, and, consequently, to low sensitivity of such markers. In this regard, we evaluated the levels of these cytokines in MNC cultures isolated from the peripheral blood of patients in the study groups. The obtained data showed that the concentrations of cytokines IL-1, IL-6, IL-10 and TNFα in cell culture are ten-fold higher than their concentration in peripheral blood, while they are significantly increased in elderly and long-living participants compared with young participants. Increased production of IL-6 and TNFα was also detected in the group of elderly and longliving participants with a pathological aging phenotype. At the same time, the concentration of the anti-inflammatory cytokine IL-10 also increased with age, but did not depend on the aging phenotype, which characterizes the revealed imbalance of pro- and anti-inflammatory cytokines in the pathological aging phenotype.

CONCLUSIONS. The identified markers of the pathological and normal aging phenotypes help predict the development of age-associated pathology or longevity. Our proposed study of cytokines in MNC culture may be more informative than the assessment of cytokines in peripheral blood serum.

BACKGROUND. A trend toward demographic aging of the population is currently observed in most countries worldwide. More and more people are achieving longevity, both due to environmental factors and lifestyle, as well as to molecular genetic processes. Few large-scale studies have examined all factors contributing to longevity both in Russia and globally. Fewer of them have used a multi-omics approach, which could provide a better insight into the phenomenon of longevity by integrating genomic, epigenomic, transcriptomic and metagenomic data. AIM. To study the longevity phenomenon in the Russian Federation using a comprehensive analysis of lifestyle, environmental, socio-economic, clinical and laboratory factors, as well as molecular genetic factors.

MATERIALS AND METHODS. The five-year joint longevity study conducted by the Center for Strategic Planning and the Russian Clinical Research Center for Gerontology has successfully collected one of the world’s largest repositories, containing a unique database of over 20,000 biological samples from 5,000 long-living individuals from 10 regions of the Russian Federation. Each participant undergoes a detailed medical history analysis, a comprehensive geriatric assessment, a wide range of laboratory tests, and molecular genetic testing.

RESULTS. An integrated approach to the study of longevity enabled the determination of main aging phenotypes, as well as the environmental and lifestyle factors associated therewith. The longitudinal design of the study also allowed for the identification of factors related to all-cause mortality, including mortality from COVID-19. State-of-the-art sequencing provided an opportunity to examine the molecular genetic factors underlying both longevity (86 genetic variants passed the genome-wide significance threshold for longevity, 2 of which were located in the coding region in the APOE gene) and socially significant geriatric syndromes, such as cognitive impairment (19 genetic variants passed the genome-wide significance threshold, several of which were also located in the APOE gene). The results of the genome-wide association studies have been used in the development of a polygenic score model that enables to assess an early risk for cognitive impairment with 69% accuracy and the longevity probability with 78% accuracy. The results were validated on independent cohorts, as well as in vitro and in vivo models. In addition to the genetic data analysis, the epigenetics of longevity has also been studied. The epigenetic data obtained during the study have enabled the development of a biological age assessment tool with an accuracy of 95%, outperforming other comparable models.

CONCLUSIONS. This comprehensive approach, considering both multi-omics and clinical data, could facilitate the development of highly accurate predictive models for aging-associated diseases and biological age assessment models. It provides a better insight into the fundamental mechanisms of longevity and promotes personalized geriatric medicine.

BACKGROUND. Validation of the SCORE2 scale in the Russian population showed high accuracy in assessing cardiovascular risk (CVR) in men, but not in women. The development of new methods for assessing CVR in women is therefore an urgent task. A number of mammographic parameters, such as breast calcification (BC) and breast density (BD) can be additional biomarkers of cardiovascular diseases in women.

AIM. To assess the relationship between the results of a retrospective analysis of mammograms and CVR in women aged 65 years and older.

MATERIALS AND METHODS. Retrospective analysis involved the mammograms of 570 patients who subsequently underwent medical examinations at the Research and Educational Center of the Moscow State University. BD and BC were assessed based on scales developed by the American College of Radiology. The CVR was assessed in accordance with the Guidelines of the Russian Society of Cardiology. Statistical analysis was performed using the open-source R 4.1 environment.

RESULTS. A relationship was found between mammographic parameters and CVR in women aged 65 years and older. Low BD, the presence and prevalence of BC were associated with higher CVR. The vascular type of calcifications was typical for patients with high and very high CVR. The absence of statistically significant differences in the density and calcification between the right and left mammary glands will be considered when developing an integral marker to verify the obtained results.

CONCLUSIONS. A method for secondary analysis of preventive mammography data can help assess the CVR and determine rational routing of patients within the framework of the second stage medical examination. Downward reclassification of cardiovascular risk factors will help avoid unnecessary prescription of statins, while upward reclassification will help prescribe optimal treatment and provide additional motivation for women to correct cardiovascular risk factors.

BACKGROUND. Global population aging leads to an increased rate of agerelated diseases such as arterial hypertension. Existing diagnostic methods are limited by the insufficient sensitivity of clinical and laboratory markers and the restrictions of conventional statistical methods. This highlights the need for new approaches to medical data analysis. This study is aimed to identify new laboratory markers of arterial hypertension using machine learning models and to compare their effectiveness compared with conventional methods. It involved the analysis of clinical and laboratory data of 2,228 patients over 65 years of age who sought medical advice at the clinic of the Medical Research and Educational Center of Lomonosov Moscow State University. Logistic regression with regularization, random forest, and gradient boosting were employed. Effectiveness was assessed using the AUC ROC, while attribute contributions were assessed by means of SHAP analysis. Machine learning models outperformed conventional logit regression. Gradient boosting achieved an AUC ROC of 0.85 compared to 0.78 for regression methods. The key attributes associated with arterial hypertension were age, RDW-SD value and creatinine levels, whereas conventional methods focused mainly on age. The conclusions confirm the high potential of machine learning methods in diagnosing age-related diseases. These models ensure higher accuracy and reveal complex interrelationships between indicators, which can improve early diagnosis and optimize diagnostic algorithms. Population aging is a global demographic trend leading to an increase in the incidence of agerelated diseases [1]. Early and accurate diagnosis of these conditions is becoming particularly important for effective treatment and minimization of the risk for complications in elderly patients. However, current diagnostic algorithms are often limited by the insufficient sensitivity and specificity of clinical and laboratory markers, while standard data analysis methods may not always detect hidden or nonlinear dependencies that are critical for diagnosis and prognosis assessment [2]. This necessitates the development of new approaches to interpretation of medical data and identification of more precise diagnostic criteria. Advances in machine learning (ML) and artificial intelligence (AI) offer new possibilities for the analysis of large and complex medical datasets. These methods allow uncovering complex and nonlinear relationships between various parameters, which can significantly enhance our understanding of pathogenesis, improve diagnostic accuracy, and increase the treatment effectiveness of age-related diseases in conditions of global population aging [3, 4].

AIM. To identify new laboratory markers associated with arterial hypertension using ML models and to evaluate their effectiveness in comparison with conventional statistical methods.

MATERIALS AND METHODS. A retrospective analysis was performed on a database containing clinical and laboratory indicators of 2,228 patients over 65 years of age who were affiliated with the Medical Research and Educational Center of Lomonosov Moscow State University and sought medical advice or underwent preventive examinations from 2020 to 2021. Data preprocessing included handling of missing values, dealing with outliers, and normalization of attributes. In this pilot study conducted to refine the analytical tools, the presence of arterial hypertension was considered the target variable. Binary logistic regression, a standard and widely accepted method for identification of disease markers, as well as ML models such as logistic regression with regularization, a random forest model, and gradient boosting were employed. The performance of these methods was assessed using the area under the ROC curve (AUC ROC). The contribution of each attribute was interpreted using the SHAP analysis.

RESULTS. The ML models have been proven to be superior compared with conventional logistic regression. Gradient boosting achieved an AUC ROC of 0.85, whereas logistic regression showed an AUC ROC of 0.78 (Fig. 1). The most important attributes associated with the presence of arterial hypertension were age, red blood cell distribution width (RDW-SD), and creatinine levels. Meanwhile, the standard regression analysis relied primarily on age (Fig. 2, 3). Age and creatinine levels were expectedly significant factors, while RDW-SD, typically evaluated in the context of anemia and associated with erythropoiesis, was also identified as a significant marker of arterial hypertension. These findings may indicate a broader relationship between inflammatory processes and the state of erythropoiesis with the development of arterial hypertension.

CONCLUSIONS. Our findings reveal the high potential of ML models in medical diagnostics for identification of new laboratory markers of age-related diseases. ML methods not only provide higher predictive accuracy but also uncover complex, previously unknown relationships between clinical and laboratory indicators and the onset and progression of diseases. Unlike conventional statistical methods, they account for nonlinear and multidimensional interactions between features. These findings can serve as a basis for further clinical research aimed at confirming the associations found and developing new targets for intervention, potentially leading to changes in diagnostic and treatment approaches. Implementation of these models in clinical practice may improve early diagnosis of age-related diseases, reduce morbidity and mortality, and ultimately enhance patient quality of life. 

BACKGROUND. Methods for slowing down aging processes and progressing of age-associated diseases are being extensively studied. To make significant discoveries in this area, scientists need data on elderly patients, primarily as the target subject of the research rather than a subgroup in the general sample of all ages. Meanwhile, doctors face difficulties in establishing and maintaining longterm contact with elderly patients both at the stage of inclusion in the study and during examination and treatment. Ignorance of the specifics of communication with elderly patients often leads to a complete loss of the patient’s trust and the cessation of interaction with the doctor.

AIM. To describe key elements of interaction with elderly and senile patients and to identify tools for establishing trust during the initial conversation.

MATERIALS AND METHODS. A cross-sectional observational study design was used to collect and analyze data from the initial interaction between the doctor and elderly and senile patients. RESULTS. A total of 166 people aged 65 to 90 years (median age: 77 years) underwent primary screening before inclusion in the clinical trial, which included medical history collection, examination, and assessment of available laboratory and instrumental data. All participants were informed that the study would require a noninvasive examination to assess vascular stiffness and a single blood draw from a peripheral vein. Despite full compliance with the inclusion/exclusion criteria, 42 patients (24.7%) did not sign informed consent for participation. When analyzing the reasons for refusing to participate in the study (data was indicated voluntarily in the questionnaire without the presence of a doctor and/or in person at a doctor’s appointment), the most common reasons were as follows: fear of fraud, fear of the need for repeated interactions (it would be necessary to come regularly to give blood / perform other invasive procedures), unwillingness to learn additional information about the state of their health and prognosis, fear of the personal data use outside the limits of medical purposes; the reason for not wanting to “create a medicine/weapon based on my blood” was also repeatedly indicated. In 63% of cases, elderly patients tried to transfer responsibility for a decision to their relatives or the doctor themselves. The main reasons for voluntary consent to participate in the study were as follows: hope for additional attention from medical personnel, the possibility of additional direct contact with a doctor (without an appointment), altruistic reasons.

CONCLUSIONS. Lack of trust in communication between doctors and elderly/ senile patients is a major issue in the medical environment. Building trust in the healthcare sector is crucial for forming effective long-term relationships with patients. Empathy, patience, transparency and medical expertise are the key pillars of trust for elderly patients. Methods of active listening, clear communication, limiting the use of medical terminology, predictable schedule in communication contribute to increasing empathy and transparency in the relationship and thus to building trust. Constantly updat of medical knowledge and providing a second expert opinion demonstrates the medical experience of the doctor to the elderly patient and also contributes to building trust.

BACKGROUND. More than one hundred candidate genes have been associated with longevity, including APOE, FOXO1A, GF1, IGF1, INCR, TP53, etc. Despite extensive research, the precise molecular and genetic underpinnings remain elusive due to the low reproducibility of the findings. Moreover, most studies have focused on exomes and have neglected intergenic regulatory regions of DNA.

AIM. To examine the genetic and molecular basis of longevity and create a prognostic model that assesses the chance of reaching the age of 90.

MATERIALS AND METHODS. To study the genetic predictors of longevity, 10,157 people were recruited, including 3,066 long-living individuals (90+ years). The recruitment of long-living individuals was carried out jointly with the Russian Clinical Research Center for Gerontology; other participants have been included from the database of the Center for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical-Biological Agency. A comprehensive medical history was collected for all participants (including data on chronic conditions), and wholegenome sequencing of blood cell DNA was performed. When determining the healthy long-living individuals, we have utilized the machine learningbased calculator of aging phenotype previously developed by us [1].

RESULTS. A genome-wide association study (GWAS) involving 3,066 longliving individuals (90+ years) and 7,091 people aged 18 to 75 years confirmed the known association of APOE gene variants with longevity. Additionally, we discovered new associations in the TMEM59, LRRC7, FHIT, CPLX1, DDX31, GRIN1, DHX32, CACNA1C, FBXO21 and UBBP4 genes. The obtained results helped construct a polygenic score, which assesses an individual chance of becoming a long-living individual (ROC AUC = 0.78). However, long-living individuals are a phenotypically heterogeneous group, so determining only the chance of living to 90 years may not be enough. The functional status at this age should also be addressed. The genomes of healthy long-living individuals were compared with the genomes of ailing long-living individuals and those of a healthy population sample. Healthy longevity is mediated by completely different molecular mechanisms than the broader phenotype, and is associated with the genes NAV1, SDK1, ARHGAP39 and ITGAE. Regulatory RNAs, particularly the antisense RNA to the mRNA of the IPO9 gene product, were shown to significantly affect healthy longevity.

CONCLUSIONS. This study of the genetic basis of longevity has shown that there is no single mechanism that would be a single and key predictor for life expectancy. Longevity has been and remains a multifactorial phenomenon. However, this work confirmed the association of variants in the APOE gene with life expectancy in the Russian population, as well as detected many new polymorphisms associated with longevity. A polygenic scale was proposed that predicts the chance of reaching the age of longevity with an accuracy of over 78%. The important role of regulatory regions of the genome in the phenotype formation was specifically highlighted. Moreover, the achievement of healthy longevity turned out to be mediated by completely different molecular mechanisms than the broader phenotype, and is associated with the genes NAV1, SDK1, ARHGAP39, and ITGAE.

BACKGROUND. Alzheimer’s disease (AD) is the most common neurodegenerative disease that causes memory loss predominantly in eldely and senile people [1]. AD is one of the most common causes of death within 5–12 years after the first detected symptoms. Modern drugs approved by the FDA (U.S. Food and Drug Administration) for the AD treatment (memantine, tacrine, rivastigmine, galantamine, donepezil) do not significantly slow down the disease progression [2] and have a wide range of side effects [3]. In view of the lack of effective treatment, the rising global prevalence of AD and significant costs of patient life support, finding effective and safe potential anti-AD drugs is becoming increasingly critical in the context of a global trend towards longer life expectancy. Peptide bioregulators are promising neuroprotectors with low immunogenicity and high physiological activity. In particular, AD therapy may benefit from studying the activity of EDR and KED short peptides obtained by analysis of amino acid composition of extracts isolated from cattle brain and vessels, respectively. AIM. To evaluate the efficacy of short peptides in in vitro and in vivo models of Alzheimer’s disease with a view to developing a drug for the treatment and prevention of this pathology.

MATERIALS AND METHODS. A neuronal culture isolated from the brain of newborn wild-type mice, with the addition of synthetic oligopeptides Aβ (the amyloid synaptotoxicity model) was used as the in vitro model of AD. The study groups were as follows: Group 1: control (without Aβ); Group 2: control with the addition of Aβ; Group 3: the addition of Aβ and EDR peptide (200 ng/mL); Group 4: the addition of Aβ and KED peptide (200 ng/mL). Series of neuron microphotographs were obtained using the ThorLabs confocal microscope and ThorLabs software (USA) at the 100-fold magnification (Olympus UPlanSApo) with resolution 1024×1024, which were used for dendritic spine morphology analysis using NeuronStudio software package according to [4]. The transgenic line of 5xFAD-M mice derived by cross-breeding of 5xFAD and Thy1-GFP mice was used as an in vivo model of AD. The experimental groups were as follows: Group 1: control (a line of healthy mice, which received the injections of physiological solution); Group 2: 5xFAD-M line of mice (AD model), which received the injections of physiological solution; Group 3: 5xFAD-M line of mice (AD model), received the injections of EDR peptide; Group 4: 5xFADM line of mice (AD model), received the injections of KED peptide. Short peptides were intraperitoneally injected in mice aged from 3 to 5 months on a daily basis. At the age of 5 months, the animals underwent transcardial perfusion followed by brain extraction; fixed brain slices (40 μm thick) were prepared using a vibratome. Series of neuron microphotographs were obtained using the ThorLabs confocal microscope and ThorLabs software (USA), followed by morphometric analysis of dendritic spines. RESULTS. EDR peptide at the concentration of 200 ng/mL increased the number of the most functional mushroom spines of neurons (by 71%) to normal levels in the primary neuronal culture under amyloid synaptotoxicity conditions (in vitro AD model). KED peptide at the concentration of 200 ng/mL increased the number of mushroom spines by 20% in the AD model. Daily intraperitoneal injection of EDR and KED peptides at a concentration of 400 μg/kg to 5xFAD mice (in vivo AD model) aged from 3 to 5 months contributed to statistically significant increases in mushroom spines in the CA1 area of the hippocampus by 25% and 27%, respectively. These peptides contributed to the increase in the total dendritic density by 13% and 22%, respectively.

CONCLUSIONS. The obtained results demonstrate that EDR and KED short peptides have a neuroprotective effect in the AD model, manifested by an improved functional state of neurons. Further research is needed to identify the mechanism of action of short peptides in AD in order to develop a drug for the prevention and treatment of this pathology.

BACKGROUND. Leptin is involved in the development of some age-related pathological conditions, in particular, metabolic syndrome, obesity, diabetes mellitus and atherosclerosis. Considering the population aging and high prevalence of cardiovascular diseases and related mortality in the older age group, it is quite important to study various risk factors for cardiovascular pathology (including hyperleptinemia) in the very old and long-living population.

AIM. To determine the concentration of leptin and to analyze the relationships of this adipokine with obesity and a number of other pathological conditions in very old and long-living patients with coronary artery disease (CAD).

MATERIALS AND METHODS. This work was a cross-sectional study. A total of 110 very old patients were enrolled in the study: 90 patients with CAD in the study group and20 patients without CAD in the control group. Mean age of the patients was 88.5 + 4.5 years; 48.2% of patients were ≥ 90 years. The serum leptin concentration was determined by enzyme-linked immunosorbent assay. Normal leptin values were 2.6–11.1 ng/mL for women, and 2.0–5.6 ng/mL for men. The content of adipose tissue in the body was assessed by dual-energy X-ray absorptiometry.

RESULTS. Elevated serum leptin concentration was found in 58.2% of patients (decreased in 16.4%, normal in 25.4%). Increased leptin concentration was found in 67.1% of women and in 40.5% of men (p = 0.007). In patients with CAD, mean concentration of leptin reached 16.7 ng/mL; in patients without CAD, 15.3 ng/mL (p = 0.6). In patients with chronic heart failure, the probability of detecting low leptin levels increased by 3.2 times, compared with patients without heart failure (OR = 3.2; 95% CI = 1.1–9.9; p = 0.03). In patients with obesity, the mean leptin concentration was 28.5 ng/mL, while in patients without obesity it comprised 12.2 ng/mL (p = 0.00002). Significant correlation was found between the leptin concentration and body mass index (p < 0.000001). Significant positive correlation was registered between the serum leptin level and the adipose tissue content (p = 0.000001). The leptin concentration positively correlated with the concentration of total cholesterol (p = 0.02) and triglycerides (p = 0.003) in the blood serum. Patients with diabetes mellitus had higher leptin values (26.3 ng/mL vs 13.5 ng/mL in the group of patients without diabetes; p = 0.0003); a significant direct correlation was found between the concentration of leptin and glucose in the blood serum (p = 0.0003). In patients with low leptin concentration, lower bone mineral density was registered (p = 0.0003).

CONCLUSIONS: The study results suggest frequent leptin pathology in elderly and long-living patients, both with and without coronary artery disease. Higher leptin levels are associated with various metabolic disorders (obesity, dyslipidemia, and diabetes mellitus). Lower leptin levels are typical for patients with chronic heart failure.

BACKGROUND. Studies on body composition in long-living patients, especially using dual-energy absorptiometry, are almost unknown. AIM. To investigate body composition in patients over 90 years old (long-living patients) with coronary artery disease (CAD).

MATERIALS AND METHODS. This work was a cross-sectional study that enrolled 200 patients (140 women and 60 men, mean age 92.4 ± 2.3 years) with CAD. Body composition was analyzed using dual-energy X-ray absorptiometry.

RESULTS. Overweight or obesity were diagnosed in 69.5% of patients. Obesity was reported in 29.0% of patients: 77.6% of them had class I obesity, while class III obesity was not observed at all. Mean values of the body mass index (BMI) were 27.6 ± 4.5 kg/m2 (18.2–38.8 kg/m2). Women had a higher proportion of fat in all areas of the body. The adipose tissue content in the upper limbs was 1.6 kg in men and 2.2 kg in women (p < 0.0001); in the lower limbs, these values were 5.7 kg and 8.1 kg, respectively (p < 0.0001). The ratio of the adipose tissue in the lower limbs to the total fat content reached 0.40 in women and 0.27 in men (p < 0.0001). The ratio of trunk fat to total fat was 0.53 in women and 0.62 in men (p < 0.0001). Mean values of bone mineral density (BMD) as a whole were 1,008 ± 140 mg/cm3; the T-score reached -1.7SD. The lowest BMD values were registered in the ribs (626 mg/cm3). In women, all BMD values were significantly lower than in men; the greatest differences were noted for BMD of the lower and upper extremities (p < 0.0001). The total lean tissue content was 38.4 kg in women and 48.8 kg in men (p < 0.0001). The musculoskeletal index remained within normal in 72.1% of patients. A decrease in this index was reported in 25% of women and 33% of men. A direct correlation was established between BMI and BMD in all areas of the skeleton (r = 0.5; p < 0.0001). A highly significant direct correlation was found between the adipose tissue content in all areas of the body and BMD; the most significant values were registered for the correlation between BMD of the ribs and the fat mass in the trunk (r = 0.85; p < 0.0001). A significant correlation was observed between the lean tissue and BMD; the most significant relationship was registered for BMD of the upper limbs and the lean tissue in the upper limbs (r = 0.69; p < 0.0001). An inverse correlation was recorded between the adipose tissue and lean tissue; the most significant relationship was found in the lower limbs (r = -0.46; p < 0.0001). Sarcopenic obesity was observed in 5% of patients, osteosarcopenic obesity in 2%, and a combination of osteoporosis with obesity in 8.7%. Normal BMD values in combination with the absence of sarcopenia and obesity were registered in 16.5% of patients.

CONCLUSIONS. The study results indicate the specific features of body composition in long-living patients A high proportion of patients with excess body weight, but with normal BMD and lean tissue mass was found.

BACKGROUND. With aging, the concentration of proinflammatory mediators increases even in the absence of signs of inflammation (“inflammaging”). AIM. To determine the serum concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and to analyze the relationships of these proinflammatory cytokines with a number of pathological conditions in very old and long-living patients with coronary artery disease (CAD).

MATERIALS AND METHODS. The study enrolled patients over 75 years of age. The study on TNF-α enrolled 130 patients (102 with CAD in the main group, 28 without CAD in the control group). The mean age of patients was 89.3 ± 4.6 years (77–101 years); more than half (56.2%) were over 90 years old. The study on IL-6 enrolled 128 patients (94 patients with CAD in the main group, 34 without CAD in the control group). The mean age of patients was 88.3 ± 5.3 years (76–98 years); 49.2% were over 90 years old. The concentration of TNF-α (N < 8.1 pg/mL) and IL-6 (N < 7.0 pg/mL) was determined by enzyme-linked immunosorbent assay.

RESULTS. The mean TNF-α concentration was 9.2 ± 4.7 pg/mL (3.9– 31.9 pg/mL). Increased TNF-α was found in 54.6% of patients. In patients with CAD, mean TNF-α concentration reached 10.0 ± 4.9 pg/mL, while in the control group it was 6.1 ± 1.8 pg/mL (p = 0.000001). The probability of detecting an elevated TNF-α level in patients with CAD increased by 16.6 times compared with patients without CAD (odds ratio (OR) = 16.6; p < 0.00001). The TNF-α concentration was higher in patients with chronic heart failure (CHF) (p = 0.002). In patients with hyperuricemia, mean TNF-α level was 10.9 ± ± 5.3 pg/mL, while in patients with normal uric acid levels it was 7.5 ± 2.5 pg/mL (p = 0.000006). Direct correlations were found between the concentrations of TNF-αand uric acid (r = 0.45; p < 0.000001), creatinine (r = 0.26; p = 0.002), urea (r = = 0.37; p = 0.00004), type I collagen degradation products (β-CrossLaps) (r = 0.53; p = 0.0001) and IL-6 (r = 0.39; p = 0.007). Inverse correlations were found between the concentration of TNF-α and HDL-cholesterol (r = -0.38; p = 0.00005). In patients under 90 years of age, mean TNF-α concentration reached 10.5 pg/mL, while in long-living patients it was 8.1 pg/mL (p = 0.003). Elevated IL-6 levels were found in 45.3% of patients. Mean IL-6 concentration was 8.2 ± 6.3 pg/mL (1.5–36.2 pg/mL). In patients with CAD, mean IL-6 concentration reached 9.0 pg/mL, while in those without coronary artery disease it was 5.8 pg/mL (p = 0.001). The probability of detecting elevated IL-6 concentrations in patients with CHF increased by 3.1 times, compared with the group without heart failure (OR = 3.1; p = 0.005). Among patients with asymptomatic hyperuricemia, mean blood concentration of IL-6 reached 10.8 ± 4.8 pg/mL, while in patients with normal uric acid levels it comprised 6.9 ± 4.5 pg/mL (p = 0.001). Patients with elevated IL-6 levels had lower values of baseline functional activity according to the Barthel index (70.7 and 80.7, p = 0.003) and instrumental activity according to the IADL scale (3.4 and 5.0, p = 0.0002).

CONCLUSIONS. The study results indicate a frequent increase in the blood concentration of TNF-α and IL-6 in very old and long-living patients with CAD. Higher levels of TNF-α and IL-6 are associated with CHF and hyperuricemia.