This study aimed to identify disease progression specific to older patients through cluster analysis of blood biomarkers and lifestyle. The most significant variables, including hormonal and metabolic parameters, as well as the results of a comprehensive geriatric assessment, help stratify older people into groups according to the severity of sarcopenia. The identified association between blood biomarkers, lifestyle factors, and sarcopenia progression among older adults could contribute to the development of more effective treatment and prevention strategies. The European Working Group on Sarcopenia in Older People (EWGSOP2) defines sarcopenia as a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age. New findings on the hormonal and metabolic characteristics of patients with sarcopenia have aided in developing more targeted therapeutic strategies. However, treating older patients with sarcopenia still poses a number of challenges. Despite numerous studies on sarcopenia, no comprehensive phenotyping of older sarcopenic patients has yet to be offered. Cluster analysis has been successfully used to study various diseases. It may be extremely advantageous for collecting data on specific sarcopenia progressions based on a simultaneous assessment of a whole range of factors. To identify disease progression specific to older patients based on cluster analysis of blood biomarkers and lifestyle. This study included 1709 participants aged 90 and older. The median age was 92. Seventy-one percent of participants were female. Participants underwent a comprehensive geriatric assessment and had their metabolic, hormonal, and inflammatory blood biomarkers measured. The data were analyzed and clustered using the R programming language. Seven sarcopenia clusters were identified. The most significant variables, in descending order, were malnutrition, physical activity, body mass index, handgrip strength, testosterone, albumin, sex, adiponectin, total protein, vitamin D, hemoglobin, estradiol, C-reactive protein, glucose, monocytes, and insulin. Handgrip strength measurements and free T3 levels increased linearly between the cluster with the lowest measurements and the cluster with the highest measurements. The findings of this study may greatly aid in understanding the relationship between blood biomarkers, lifestyle and sarcopenia progression in older adults, and may help in developing better prevention and diagnostic strategies as well as more personalized therapeutic interventions.

RELEVANCE: Sarcopenia is one of the leading geriatric syndromes that increases the risk of disability, falls and injuries. This syndrome is of particular importance for centenarians aged 90 years and older, for whom a detailed analysis of the course of sarcopenia has not previously been carried out and the hormonal and metabolic characteristics of this condition have not been described.AIM OF THE STUDY: To analyze the features of hormonal and metabolic status in nonagenarians with sarcopenia and to identify factors that increase the risk of developing this conditionMATERIALS AND METHODS: The study included 2221 people over the age of 90 years. Study participants underwent a comprehensive geriatric assessment during a visit with a doctor and nurse, as well as blood tests to measure a number of metabolic and hormonal parameters. Statistical data analysis was carried out using the R programming language version 4.2.2.RESULTS: Apolipoprotein A1, free triiodothyronine, vitamin D, albumin, C-reactive protein, hemoglobin, red blood cells and hematocrit were significantly associated with the presence of sarcopenia. In a survival analysis of people with sarcopenia, the strongest protective factors for participants with sarcopenia were any physical activity and increasing free T3. Malnutrition is the leading destructive factor.CONCLUSION: Hormonal metabolic status, in particular low concentrations of vitamin D, triiodothyronine, albumin, and apolipoprotein A1, largely determines the presence of sarcopenia in centenarians, but when assessing risks, it is necessary to take into account a number of other important parameters, such as physical activity and nutritional status.

Carotenoids are one of the largest classes among biological pigments. They are found both in free form (dissolved in hydrophobic environments), and bound in stoichiometric complexes with protein (carotenoproteins). The interaction between the carotenoid and the protein environment is determined by the molecular conformation and dynamic behavior of the cofactor. In this work, using molecular modeling methods, we analyzed the entire set of alternative conformational states of cyclic carotenoids. The result of the theoretical study is an energysorted catalog of alternative conformational states for biogenic cyclic carotenoids and their optical isomers. The conformational states characterized in this study can be used to correctly select initial conditions when solving problems of molecular modeling of carotenoproteins

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 mechanisms underlying these disorders have yet to be identified. APOE is a gene that encodes apolipoprotein E (APOE). SNVs in the APOE gene have been linked to both neurodegenerative disorders (rs429358, C112R) and protective effects against them (rs7412, R158C). Humans carry three apolipoprotein E isoforms: ε2 (a protective mutation), ε3 (wild-type protein), and ε4 (a pathogenic mutation). The study sought to investigate how these substitutions affect the functional region of the protein, i.e., the lipid-binding site. A molecular dynamics simulation was used to analyze all three isoforms. We found that both the pathogenic and protective mutations caused changes in the lipid-binding site, but not the wild-type isoform. The changes, however, were different. 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; in ε4, it unwound at 260–266. The opposite was true for the N-terminal helix. It is safe to assume that these structural differences in the lipid-binding site account for the different effects of these two isoforms and the clinical profiles of their carriers. The clustering analysis helped identify the structures most typical for ε2 and ε4. These structures could be used as the foundation for further molecular dynamics studies.

BackgroundCognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options.MethodsWe assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression).ResultsBoth variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein.ConclusionThese changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

An Erratum to this paper has been published: https://doi.org/10.1134/S1063774521340058

Many serious medical conditions are caused by the accumulation of amyloid aggregates in tissues and organs. One of the most well-known amyloidogenic proteins is the prion protein (PrP), which may undergo conformational change between the normal cellular isoform PrPC and the aggregation-prone isoform PrPSc. Elucidation of this conformational transition is necessary for understanding the onset and propagation of prion diseases. However, the flexibility of PrP hinders its research by the experimental methods of protein structure determination. Here, we implement de novo protein modelling and molecular dynamics simulations to predict the interdomain interactions of the full-length PrPC. Our theoretical findings can serve as the basis for mutational analysis and for further studies of the amyloidogenic behavior of the prion protein.