Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals—people over the age of 90 who managed to retain much of their health and functionality—could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

There is no single universal biomarker yet to estimate overall health status and longevity prospects. Moreover, a consensual approach to the very concept of aging and the means of its assessment are yet to be developed. Markers of aging could facilitate effective health control, more accurate life expectancy estimates, and improved health and quality of life. Clinicians routinely use several indicators that could be biomarkers of aging. Duly validated in a large cohort, models based on a combination of these markers could provide a highly accurate assessment of biological age and the pace of aging. Biological aging is a complex characteristic of chronological age (usually), health-to-age concordance, and medically estimated life expectancy. This study is a review of the most promising techniques that could soon be used in routine clinical practice. Two main selection criteria were applied: a sufficient sample size and reliability based on validation. The selected biological age calculators were grouped according to the type of biomarker used: (1) standard clinical and laboratory markers; (2) molecular markers; and (3) epigenetic markers. The most accurate were the calculators, which factored in a variety of biomarkers. Despite their demonstrated effectiveness, most of them require further improvement and cannot yet be considered for use in standard clinical practice. To illustrate their clinical application, we reviewed their use during the COVID-19 pandemic.

Background. The trend towards aging of the population is global, which makes the study of etiology, prevention and treatment of age-related disorders relevant. Increasing number of studies highlights the influence of 25-hydroxyvitamin D deficiency on health state in older people, as well as its correlation with geriatric syndromes prevalence. However, at the moment it is not known whether these patterns persist in patients older than 90 due to the limited number of studies on this population.Aim. To assess the prevalence of vitamin D deficiency in a cohort of centenarians in the central region of Russian Federation and to study its relationship with the presence of geriatric syndromes.Materials and methods. The study was carried out by Russian Gerontology Research and Clinical Centre of Pirogov Russian National Research Medical University and Center for Strategic Planning and Management of Medical and Biological Health Risks. It was a cross-sectional study on the cohort of centenarians (90 years and older). Complex geriatric assessment was performed. Complex geriatric assessment included past medical history, geriatric scales and questionnaires (MMSE, SARC-F, MNA scores). Blood samples were taken to assess the 25-OH vitamin D levels using chemiluminescence method. The study is reviewed by the ethics committee (№ 30 24.12.2019). The statistical analysis was performed using Python version 3.9 and R version 4.1.3.Results. The study included 3,235 people aged 90 to 107 years. Median level of 25-hydroxyvitamin D was 9 ng/ml, 86.7% of participants were found to be 25(OH)D deficient, and in 8.3% insufficiency 25(OH)D was detected. Using the intergroup analysis, the association between 25-OH vitamin D levels and some geriatric syndromes, such as malnutrition, sarcopenia and cognitive impairment was observed. However, after adjusting to physical activity and nutrition statistically significant association was demonstrated only for cognitive impairment.Conclusion. The results obtained on the association between low levels of 25-OH vitamin D and cognitive impairment among centenarians confirm the importance of vitamin D deficiency prevention and might be starting point for future studies.

Neurodegenerative disorders, particularly Alzheimer’s disease, have become a major global healthcare issue. Despite extensive research, the molecular

Previous studies examining the molecular and genetic basis of cognitive impairment, particularly in cohorts of long-living adults, have mainly focused on associations at the genome or transcriptome level. Dozens of significant dementia-associated genes have been identified, including APOE, APOC1, and TOMM40. However, most of these studies did not consider the intergenic interactions and functional gene modules involved in cognitive function, nor did they assess the metabolic changes in individual brain regions. By combining functional analysis with a transcriptome-wide association study, we aimed to address this gap and examine metabolic pathways in different areas of the brain of older adults. The findings from our previous genome-wide association study in 1155 older adults, 179 of whom had cognitive impairment, were used as input for the PrediXcan gene prediction algorithm. Based on the predicted changes in gene expression levels, we conducted a transcriptome-wide association study and functional analysis using the KEGG and HALLMARK databases. For a subsample of long-living adults, we used logistic regression to examine the associations between blood biochemical markers and cognitive impairment. The functional analysis revealed a significant association between cognitive impairment and the expression of NADH oxidoreductase in the cerebral cortex. Significant associations were also detected between cognitive impairment and signaling pathways involved in peroxisome function, apoptosis, and the degradation of lysine and glycan in other brain regions. Our approach combined the strengths of a transcriptome-wide association study with the advantages of functional analysis. It demonstrated that apoptosis and oxidative stress play important roles in cognitive impairment.

Neurodegenerative disorders, particularly Alzheimer’s disease, have become a major healthcare issue all over the world. Despite extensive research, the molecular mechanisms underlying these conditions are yet to be identi ed. APOE is the apolipoprotein E-coding gene. Its polymorphisms have been found to be signi cantly associated with both neurodegenerative disorders (rs429358, C112R) and protective e ects against these disorders (rs7412, R158C). Humans carry three apolipoprotein E isoforms: ε2 (protein with a protective mutation), ε3 (wild-type protein), and ε4 (protein with a pathogenic mutation). The study sought to investigate how these substitutions a ect the lipid-binding site, which is the functional region of the protein. Molecular dynamics simulation was used to analyze all three isoforms. We found that, unlike the wild-type isoform, both the pathogenic and protective mutations caused changes in the lipid-binding site. The changes, however, were di erent. Both ε2 and ε4 lead to an increased distance between the N-terminal (amino acids 88-104) and the C-terminal (amino acids 251-266) helices. However, in ε2, the C-terminal helix retained its structure, whereas in ε4, it unwound between amino acids 260 and 266. The opposite was true for the N-terminal helix. It is safe to assume that it is these structural di erences in the lipid-binding site that account for the di erent e ects of these two isoforms and clinical characteristics of their carriers. The clustering analysis allowed for the identi cation of the structures, most typical of ε2 and ε4, which could be used as the foundation for further molecular dynamics studies.