Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis

BackgroundPsycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied.MethodsIn 2020–2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set).ResultsThere was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326).ConclusionOur results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated

Atorvastatin therapy modulates telomerase activity in patients free of atherosclerotic cardiovascular diseases

Background— Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases. Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now this effect has not been investigated in prospective randomized studies.We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells.Methods—In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known cardiovascular diseases and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction.Results—At study end 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46±0.05 to 0.68±0.06 (p=0.004) in the atorvastatin group and from 0.67±0.06 to 0.60±0.07 (P=0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p=0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in IL-6 within the normal range and a tendency towards reductionin blood urea.Conclusions—These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector

A Cross-Sectional Study of the Gut Microbiota Composition in Moscow Long-Livers

The aim was to assess the gut microbiota of long-livers from Moscow. This study included two groups of patients who signed their consent to participate. The group of long-livers (LL) included 20 participants aged 97–100 years (4 men and 16 women). The second group included 22 participants aged 60–76 years (6 men) without clinical manifestations of chronic diseases (healthy elderly). Gut microbiota was studied by 16S rRNA sequencing. Long-livers underwent a complex geriatric assessment as well as expanded blood biochemistry. Gut microbiota composition in the cohorts was also compared with microbiome in long-livers from Japan and Italy. Russian long-livers’ microbiome contained more beneficial bacteria than healthy elderly including Ruminococcaceae, Christensenellaceae, Lactobacillaceae families. Conditional pathogens like Veillonellaceae, Mogibacteriaceae, Alcaligenaceae, Peptococcaceae, Peptostreptococcaceae were more abundant in the healthy elderly. Compared with Italian and Japanese microbiome LL, the Russian LL appeared to be more similar to the Italian cohort. Bifidobacterium/Coprococcus and Faecalibacterium/Coprococcus balances were associated with femoral and carotid intima–media thickness, respectively. Bifidobacterium/Coriobacteriaceae balance was assessed with the folic acid level and Faecalibacterium/Coriobacteriaceae_u the with Mini Nutritional Assessment score. Long-livers’ microbiome appeared to be unexpectedly balanced. The high representation of beneficial bacteria in long-livers may prevent them from low-grade inflammation and thus protect them from the development of atherosclerosis and other aging-associated conditions

Gut Microbiota in Patients with Different Metabolic Statuses: Moscow Study

The aim of this paper was to study gut microbiota composition in patients with different metabolic statuses. Methods: 92 participants aged 25–76 years (26 of whom were men), with confirmed absence of cardiovascular and other chronic diseases (but with the possible presence of cardiovascular risk factors) were included. Carotid ultrasound examinations, 16S rRNA sequencing of stool samples and diet assessments were performed. Statistical analysis was performed using R programming language, 3.1.0. Results: Enterotyping yielded two clusters differentiated by alpha-diversity. Intima-media thickness was higher in the cluster with lower diversity (adj. p < 0.001). Obesity was associated with higher Serratia (adj. p = 0.003) and Prevotella (adj. p < 0.0003) in relative abundance. Abdominal obesity was associated with higher abundance of Serratia (adj. p = 0.004) and Prevotella (adj. p = 0.0008) and lower levels of Oscillospira (adj. p = 0.0005). Glucose metabolism disturbances were associated with higher Blautia (adj. p = 0.0007) and Serratia (adj. p = 0.003) prevalence. Arterial hypertension was associated with high Blautia levels (adj. p = 0.002). The Blautia genus strongly correlated with low resistant starch consumption (adj. p = 0.007). A combination of high-fat diet and elevated Blautia levels was very common for diabetes mellitus type 2 patients (adj. p = 0.0001). Conclusion: The results show that there is a relationship between metabolic changes and higher representation of opportunistic pathogens and low diversity of gut microbiota even in apparently healthy participants

Metagenomic Profiles of the Intestinal Virome of Long-Livers

The microbial community of the human intestine is important for maintaining human health. It has been reported that the gut microbiome changes with age, and it can be enrichedwith certain beneficial bacteria while also losing certain commensal bacteria.Little is known about the gut virome of long-livers. Our research aimed to extract, sequence and analyze the viral fraction of long-livers’ gut microbiota in comparison with those of young adults and the elderly. We were thereby able to characterize the gut virome profiles and viral diversity of three age groups. Keywords: aging, gut microbiome, viral metagenomics, bacteriophage

Metagenomic Profiles of the Intestinal Virome of Long-Livers

The microbial community of the human intestine is important for maintaining human health. It has been reported that the gut microbiome changes with age, and it can be enrichedwith certain beneficial bacteria while also losing certain commensal bacteria.Little is known about the gut virome of long-livers. Our research aimed to extract, sequence and analyze the viral fraction of long-livers' gut microbiota in comparison with those of young adults and the elderly. We were thereby able to characterize the gut virome profiles and viral diversity of three age groups. Keywords: aging, gut microbiome, viral metagenomics, bacteriophage

Biological Age Predictors: The Status Quo and Future Trends

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

Effects of Traumatic Brain Injury on the Gut Microbiota Composition and Serum Amino Acid Profile in Rats

Traumatic brain injury (TBI) heavily impacts the body: it damages the brain tissue and the peripheral nervous system and shifts homeostasis in many types of tissue. An acute brain injury compromises the “brain–gut-microbiome axis”, a well-balanced network formed by the brain, gastrointestinal tract, and gut microbiome, which has a complex effect: damage to the brain alters the composition of the microbiome; the altered microbiome affects TBI severity, neuroplasticity, and metabolic pathways through various bacterial metabolites. We modeled TBI in rats. Using a bioinformatics approach, we sought to identify correlations between the gut microbiome composition, TBI severity, the rate of neurological function recovery, and blood metabolome. We found that the TBI caused changes in the abundance of 26 bacterial genera. The most dramatic change was observed in the abundance of Agathobacter species. The TBI also altered concentrations of several metabolites, specifically citrulline and tryptophan. We found no significant correlations between TBI severity and the pre-existing gut microbiota composition or blood metabolites. However, we discovered some differences between the two groups of subjects that showed high and low rates of neurological function recovery, respectively. The present study highlights the role of the brain–gut-microbiome axis in TBI

Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults

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)