Quantifying human genome parameters in aging

Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships

Evaluation of the qualitative and quantitative composition of or al microbiota in patients with medial osteonecrosis of the jaw

Aim. To determine  the qualitative and quantitative composition  of the oral microbiota in patients with medial osteonecrosis of the jaw (MOJ). Materials and methods. Microbiota was evaluated in 15 patients with medial osteonecrosis of the jaw. An assessment was made of 12 groups of optional and obligate-anaerobic microorganisms.  Evaluation of the qualitative and quantitative  composition  of oral microbiota  in patients with MOJ was performed by real-time polymerase chain reaction (PCR-RT). Results. The aerobic-anaerobic microbiota composition in patients with MOJ in the oral fluid and separated from the fistula is presented. The values of the total bacterial mass (TBM) and all anaerobic microorganisms  in the oral fluid in patients with MOJ before treatment were higher by 1-3 orders of magnitude than in healthy individuals. In the jaw, separated from the fistula in the zone of necrosis of the jaw, these parameters  were higher by 2-4 orders than in the oral fluid. Prior to surgery, a course of antibiotic  therapy was conducted  for 7 days. As a result of the therapy,  the parameters  of anaerobic  microflora  in the oral fluid decreased.  The use of cefazolin was more effective than lincomycin.  In 1 year after surgical treatment, the index of TBM and the indices of anaerobic  microorganisms  did not  differ from those of healthy  individuals. Conclusion. Patients  with medical osteonecrosis of the jaw have a high level of anaerobic pathogens in the oral microbiota. The course of antibiotic  therapy and surgical intervention  are effective methods  of treatment of MOJ,  as they lead to effective sanation, and allow further endoprosthetics

The First Experience of Creating Registers of Patients with Eye Diseases in Moscow Region

This report is devoted to the problem of absence universal databases of patients with different chronic eye diseases and continuity of these patients between medical organizations. On the basis of MONIKI there has was held a prospective, observational cohort study of patients since 2016, with diagnoses: uveal melanoma — the first group of patients, degenerative States of the optic nerve and retina (multiple sclerosis, glaucoma) — the second group, — and vascular retinal diseases (venous occlusion, diabetic retinopathy) — the third group. There were 114 patients — in the first, 68 — in the second, 92 — in the third. There were developed statistically significant parameters of patients examination, adaptation of registers to application and increase of their efficiency continues to be corrected. All patients underwent standard ophthalmological examination, in addition-gonioscopy, ultrasound (ultrasound) in a and b-scan mode, including ultrasound biomicroscopy (UBM), optical coherence tomography (OCT), fluorescence angiography (FAG), computed tomography (CT) and/or magnetic resonance imaging (MRI) of the orbit. According to the indications, patients were examined by related specialists. For each patient group, prior results were obtained. They were late detection, untimely treatment and referral patients to other medical organizations, which proves the need to systematize patients with various pathologies and the subsequent continuity of medical organizations as for the timely detection of the disease, as for adequate and timely treatment not only at the local, but also at the regional or Federal levels. The integration of patients register with various ophthalmic diseases has a priority course in the development of healthcare in the Moscow region

Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults

The clusterin (CLU) rs11136000 CC genotype is a probable risk factor for Alzheimer’s disease (AD). CLU, also known as the apolipoprotein J gene, shares certain properties with the apolipoprotein E (APOE) gene with a well-established relationship with AD. This study aimed to determine whether the electrophysiological patterns of brain activation during the letter fluency task (LFT) depend on CLU genotypes in adults without dementia. Previous studies have shown that LFT performance involves activation of the frontal cortex. We examined EEG alpha1 and alpha2 band desynchronization in the frontal regions during the LFT in 94 nondemented individuals stratified by CLU (rs11136000) genotype. Starting at 30 years of age, CLU CC carriers exhibited more pronounced task-related alpha2 desynchronization than CLU CT&TT carriers in the absence of any differences in LFT performance. In CLU CC carriers, alpha2 desynchronization was significantly correlated with age. Increased task-related activation in individuals at genetic risk for AD may reflect greater “effort” to perform the task and/or neuronal hyperexcitability. The results show that the CLU genotype is associated with neuronal hyperactivation in the frontal cortex during cognitive tasks performances in nondemented individuals, suggesting systematic vulnerability of LFT related cognitive networks in people carrying unfavorable CLU alleles

[Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer's disease patients and in normal cohorts from Russian populations].

Three genes mutations in which cause familial forms of Alzheimer's disease are known to date:PSEN1, PSEN2 and APP; and APOE gene polymorphism is a strong risk factor for Alzheimer's disease. We have evaluated allele and genotype frequency distribution of rs11136000 polymorphism in clusterin (CLU) gene (or apolipoprotein J, APOJ) in populations of three Russian regions and i nAlzheimhner's diseasepatients. Genome-wideassociation studies in samples from several European populations have recently revealed highly significant association o fCLU gene with AD (p = 8.5 x 10(-10)). We found no differences in allele and genotype frequencies of rs11136000 between populations from Moscow, Ural and Siberia regions. The allele frequencies are close to those in European populations. The genetic association analysis in cohort of Alzheimer's disease patients and normal individuals (>500 individuals ineach group) revealed no significant association of the rs11136000 polymorphism in CLU with Alzheimer's disease in Russian populations. Although our resultsdo not confirm the role of CLU gene as a majorgenetic factor forcommon form of Alzheimer's disease, the data do not rule out the possibility of modest effect of CLU and interaction between CLU and APOE genotypes in etiology of Alzheimer's disease