This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45–69) from the HAPIEE Study who had been followed up for 16 years. A nested case–control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04–1.39) to 1.44 (95% CI: 1.21–1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86–0.87 (95% CI: 0.76–0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention.

Introduction. Multisystem inflammatory syndrome associated with COVID-19 (MIS-C) is a hyperinflammatory condition with unknown pathogenesis. It is generally accepted that one of the theories that could potentially explain the pathogenesis of MIS-C is the development of autoimmune aggression. Aim. To determine the presence of autoimmunization markers in patients with COVID-19 associated multisystem inflammatory syndrome by detecting antibodies to single-stranded and native DNA. Materials and methods. A prospective multicenter study was carried out, which included 52 patients with a verified diagnosis of MIS-C. The main laboratory data were analyzed, markers of autoimmune aggression were identified by determining antibodies to single-stranded DNA, as well as antibodies to native DNA. Results. The paraclinical picture of MIS-C is based on the realization of hyperinflammatory parameters. The mean values of the corresponding inflammatory parameters were: WBC – 18.9 (12.4; 51.3); CRP – 128 (64; 398), respectively. In 35% of cases, the procalcitonin level was higher than 2 ng/ml. A number of parameters described prothrombogenic activity (the mean values of D-dimers were 1238 (684; 7840); Tr – 598 (157; 1112)), which characterized the nonspecific involvement of the vascular component in the pathological process. In the examined patients with MIS-C, no significant levels of the main autoantibodies were detected (the mean values were 34.6 (8.3; 1671.3) for antibodies to single-stranded (denatured) DNA and 30.7 (14.9; 634.8) for antibodies to native (double-stranded) DNA, with reference values of less than 20 U/ml). Conclusion. The data obtained from the study cast doubt on the potential “autoimmune” theory of MIS-C pathogenesis. Prerequisites are being formed for further search for new potential theories of MIS-C pathogenesis, including the study of a wider range of autoimmune markers, as well as the search for specific manifestations of immune dysregulation.

Currently the “rejuvenation” and an increase in the number of components of the metabolic syndrome (MS) determine its clinical significance in the earlier development of diabetes mellitus, cardiovascular diseases and related complications. Aim of the study was to investigate the features of the MS clinic picture in a population of young men and womenliving in the Khanty-Mansiysk autonomous region – Yugra.Material and methods. The study included 863 young people between 18 and 44 years of age, including 344 men and women with MS and 519 people in the comparison group. Studied subgroups are represented by non-indigenous men and women living in urban and rural areas, and indigenous rural residents. The analysis of MS clinical and laboratory parameters was carried out and its clinical variants in ethnic groups were identified.Results and its discussion. According to the results of the survey of young people with metabolic syndrome, it was revealed that the combination of abdominal obesity and two components of MS were most common in young people with MS (in 50.0 % men and in 55.5 % women). The study defined regression models for each MS group and threshold values for waist circumference were set, which changes in lipid and carbohydrate metabolism were predicted.Conclusions. In groups with MS, hypertriglyceridemia was determined as its most common component. The study identified the most frequent association of abdominal obesity with hyper-LDL cholesterol and hypertriglyceridemia in patients with metabolic syndrome, in ethnic groups, this combination is more common in indigenous rural men (53.3 %) and in non-indigenous urban women (54.3 %).

Among the many diseases that affect potato plants, viral infections are the most common and cause significant damage to farms, affecting both the yield and quality of potatoes. In this regard, an important condition for preserving the potato seed fund in Russia is systematic monitoring and early highly specific detection of potato viral infections. The purpose of the work is to study samples of potato varieties collected in the Novosibirsk region for the presence of viral infections using RT-PCR. 130 potato plants from three districts of the Novosibirsk region (NR) were studied. As a result of monitoring, the following viruses were identified: PVY (potato virus Y), PVS (potato virus S), PVM (potato virus M) and PVX (potato virus X). The quarantine pathogen potato spindle tuber viroid (PSTVd) was not detected in any of the samples analyzed. The maximum frequency of occurrence in the region was noted for three viruses: PVY, PVM and PVS. A significant proportion of the samples were mixed viral infections: the occurrence of the combination of infection PVY + PVM in plants was 25.0 %, and PVY + PVS, 22.6 %. To develop methods for determining the strain affiliation of the studied samples, the nucleotide sequences of the capsid protein genes of 10 Y-virus isolates were sequenced. Phylogenetic analysis of the studied sequences of NR isolates was carried out with a set of sequences of reference strains 261-4, Eu-N, N:O, NE-11, NTNa, NTNb, N-Wi, O, O5, SYR_I, SYR_II and SYR_III retrieved from GenBank. As a result of phylogenetic analysis, it was established that NR viral samples fell into two groups of strains: group 1, which also includes isolates of the reference strains 261-4/SYR_III, and group 2, NTNa. The obtained results of the strain affiliation of NR samples lay the basis for the development of DNA and immunodiagnostic systems for identifying PVY circulating in NR, as well as for elucidating the source and routes of entry of specific virus strains.

The gene pool of the Koryaks was studied in comparison with other Far Eastern and Siberian peoples using a genome-wide panel of autosomal single-nucleotide polymorphic markers and Y-chromosome markers. The results of analyzing the frequencies of autosomal SNPs using various methods, the similarity in the composition of Y-chromosome haplogroups and YSTR haplotypes indicate that the gene pool of the Koryaks is as close as possible to the Chukchi one and was formed as a result of the unification of several groups whose ancestors had moved from the territory of modern Yakutia and the Amur region. The two dominant Y-chromosome haplogroups of the Koryaks with different sublines of haplotype clusters demonstrate their contacts with the Chukchi, Evens, Yukaghirs, and Eskimos. Analysis of the composition of genetic components and IBD blocks on autosomes indicates the maximum genetic proximity of the Koryaks to the Chukchi. Among the Siberian populations, the Chukchi, Koryaks, and Nivkhs form a cluster separate from the main group of Siberian populations, while the Chukchi and Koryaks are more closely related. Far Eastern populations are divided in full accordance with geographic localization into the northern group (Chukchi and Koryaks) and the southern group, including the Nivkhs and Udege. A more detailed analysis of the component composition of gene pools in some populations reveals components specific to them. The isolation of such components is associated with founder effects and a shift in allele frequencies for these populations. The Koryaks and Chukchi represent one of the most striking examples of long-standing genetic kinship. Their populations demonstrate maximum values of the level of genomic inbreeding FROH > 1.5 (0.0422, 0.0409), which is natural due to their relative isolation.

Aim. To study risk factors for fatal cardiovascular events in patients with non-small cell lung cancer over two years of standard treatment.Material and methods. This pilot retrospective non-randomized cohort study included 179 patients who were consecutively admitted to the chemotherapy department of City Clinical Hospital 1 from January to December 2020 with a confirmed diagnosis of non-small cell lung cancer based on the comprehensive examination and morphological verification according to the 2018 clinical guidelines on bronchial and lung cancer. Diagnosis and treatment of cardiovascular diseases were carried out according to national clinical guidelines. The follow-up period for non-small cell lung cancer and cardiovascular disease was 2 years. Logistic regression models were considered to assess the risk of cardiovascular death. The model accuracy was assessed by a cross-validation.Results. The best model in terms of the sensitivity and specificity sum according to a cross-validation was the model with the following explanatory variables: sex, cancer stage, platinum-based chemotherapy, etoposide, immunotherapy, surgical treatment. This model showed a sensitivity of 70,1% and a specificity of 82,1%.Conclusion. This approach is easy to implement and may optimize treatment for patients with non-small cell lung cancer.

To date, the pathogenesis of COVID-19 associated multisystem inflammatory syndrome (MIS-C) remains unclear. Despite this, it becomes obvious that the pathogenesis of MIS-C is directly related to a certain immune dysregulation, however, a clear understanding of the mechanisms of this dysregulation has not yet been formulated. In order to identify the cytokine profile in patients with MIS-C, spontaneous and stimulated production of certain cytokines in cell culture was identified. Materials and methods. The study was conducted in the following study groups: group 1 — patients with MIS-C (n = 52); group 2 (comparison group) — patients with COVID-19 associated pneumonia (n = 15); group 3 (control group) — conditionally healthy patients (n = 23). The following stimulating agents were used: S58 — recombinant antigen Spike_SARS-Cov-2; NP is a recombinant NP antigen of the coronavirus SARS-CoV-2 and a standard mitogen. Results. Тhe absence of the initially expected hyperproduction of the main pro-inflammatory cytokines (IL-6, IL-8, TNF-α, etc.) was recorded. Statistically significant developments were recorded between patients of the study groups in the spontaneous production of MCP-1, in particular, the indicated indicator was 40010.82 (19698.1; 64812.1); 643.7 (214.6; 1695.4) and 622.7 (214.6; 1068.1), respectively. The indicated spontaneous hyperproduction of MCP-1 in patients with MIS-C allows us to consider as a probable completely new theory of the pathogenesis of MIS-C associated with dysregulation of the type 2 immune response. The presence of statistically significant differences, primarily in the spontaneous production of this cytokine, can apparently be explained by the presence of genetically determined determinants associated with subsequent dysfunction of the Th2 helper immune response, a potential trigger for which is a previous COVID-19 infection. Thus, further study of the immunopathogenesis of COVID-19 associated MIS-C is required.

Chronic heart failure (CHF) is a common complication of many cardiovascular diseases. It is important to study the clinical and functional features of CHF to clarify the further prognosis of this disease due to the unfavorable course and high mortality rate. Diagnosis and treatment of CHF is an issue for doctors of various specialties, in particular when it comes to geriatric patients with multiple concomitant diseases. Various physiological and morphological transformations in the aging population contribute to heart failure. The most common type of HF in older people is HF with preserved ejection fraction. Atypical clinical symptoms of CHF are much more common in elderly people than in young people. The prevalence of HF with age is associated with a longer period of influence of damaging factors on the heart, such as arterial hypertension, metabolic stress or ischemia-related damage. Due to the unfavorable course and high mortality rate, it is important to study the clinical and functional characteristics of CHF to clarify its prognosis. However, the data available on this issue vary significantly; the mechanisms, issues of diagnosis and treatment of patients with heart failure in different age groups have not been sufficiently studied, which determined the purpose of this study ‒ to investigate the features of the clinical and functional characteristics of CHF depending on age. Material and methods. The study included 90 male and female patients with diagnosed CHF stages I-IIB, NYHA functional class I-IV, aged 40–86 years, who underwent echocardiography, general and biochemical blood tests. The patients were divided into two groups: group 1 – patients of working age (women 16–54 years old and men 16–59 years old, n = 20), group 2 – patients older than working age (women 55 years and older, men 60 years and older, n = 70). Results and its discussion. According to the data obtained, the average age of all surveyed was 68.1 ± 9.8 years. The second stage of CHF prevailed in both the first and second groups of the studied categories of participants. Atypical symptoms prevailed, which creates difficulties in its diagnosis and treatment. The frequency of CHF decompensation in patients over working age, as well as the concentration of natriuretic peptide, is higher compared to the group of CHF patients of working age, which is probably due to the presence of comorbid pathology and cognitive deficit. The data obtained can be used to develop an approach to stratify the risk of CHF.

Researches aimed at studying the role of TP53 gene variability in the tumor progression of diffuse large B-cell lymphoma (DLBCL) are among the most in-demand in both the fields of fundamental and applied oncohematology. However, until recently, the knowledge about the specific mechanisms of dysfunction of this gene and their clinical significance in DLBCL was largely limited. This article is dedicated to the 300th anniversary of the Russian Academy of Sciences and describes the main scientific results of research of the molecular genetic mechanisms and the significance of p53 deregulation in DLBCL, conducted jointly by Novosibirsk State Medical University and the Research Institute of Therapy and Preventive Medicine – the Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences for many years. A comprehensive study of TP53 variability due to functionally significant polymorphisms and haplotype structure, somatic mutations, promoter methylation, as well as allelic imbalance was carried out. A two-hit mechanism for dysfunction of this anti-oncogene in the formation of lymphoma has been established. The current underestimation of the frequency of aberrations in TP53 in DLBCL is shown due to ignoring synonymous mutations and changes in non-coding regions of the gene. The deep involvement of TP53 in the processes of predisposition to development, initiation, progression and response of DLBCL to therapy has been proven. The results obtained suggest that assessment of the function of the TP53 gene and understanding the specific mechanisms of its inactivation in each of the diagnosed cases of DLBCL may soon have direct access to personalized selection of therapy.

The impact of the new coronavirus COVID-19 infection on the course of pregnancy, maternal and child health is largely unclear and controversial. The presented literature review analyzes changes in the immune, cardiovascular, and endocrine systems in women in physiological pregnancy. The peculiarities of the course of infection caused by SARS-CoV-2 virus in pregnancy, depending on the virus variant, are presented, the issues of infection pathways into immune and non-immune cells, including placental cells, as well as the issues of transplacental transfer of the virus – the key moment of infection of the embryo or fetus, on which the outcome of pregnancy also largely depends, are considered. Promising approaches to COVID-19 therapy are presented: use of inhibitors of transmembrane serine protease 2 (TMPRSS2), furin, angiotensin-converting enzyme (ACE2) and RNA-dependent RNA polymerase, amnion epithelial cells and their exosomes. At the same time, the potential use of mesenchymal stem cells in patients with severe COVID-19 pneumonia is reviewed. Difficulties and questions regarding the use of the above therapeutic methods in pregnant women are highlighted. Aspects of the use of surfactant preparations in newborns at risk of new coronavirus infection are considered.

A prospective randomized comparative placebo-controlled double-blind study was carried out based on Arterial Indices model of biological age. The study involved 60 men and women aged 40–65 years that were randomly divided into two equal groups of 30 people: the main group and the control one. The study participants from the main group received a dietary supplement containing Siberian fir terpenes, limonene, alpha-linolenic acid, and vitamin E—1 capsule 3 times a day for 90 days. Patients in the comparison group received a placebo according to a similar scheme. Anthropometric and biochemical characteristics of patients from both groups have not undergone any significant changes. According to ultrasound examination of the carotid arteries, we observed a statistically significant decrease in the minimum thickness of the intima-media complex (by 45%). The maximum carotid artery stenosis on the right or left and the expansion index in patients of both groups did not change significantly during treatment. According to the results of applanation tonometry, it was revealed that when taking the studied dietary supplement, the pulse wave velocity significantly decreased compared to the initial one (by 10%). Accordingly, the Arterial Indices biological age decreased by 2.5 years compared to the baseline level in patients of the main group and did not change in patients from the comparison group. Supplementation of fir terpenes in middle-aged patients of both sexes reduces the biological age reflecting the condition of the arteries.

Hereditary cerebellar ataxias (HCA) is a heterogeneous group of genetic neurological neurodegenerative diseases with a steadily progressive course. Ataxia is manifested by disturbed equilibrium, speech. Diseases of this group, as a rule, lead to disability of the patient. Advances in the field of molecular genetic research have made it possible to determine the form of HCA in accordance with the type of inheritance, and on this basis a classification of HCA has been formed. Monogenic (autosomal dominant, autosomal recessive, X-linked) and non-traditional types of inheritance of cerebellar ataxias (mitochondrial, expansion of trinucleotide repeats) are distinguished, sporadic forms with an unidentified or unknown type of transmission are also distinguished. Thus, HCA are classified into autosomal dominant spinocerebellar ataxias (SCA), they include 48 forms, some of which are polyglutamine SCA, and autosomal recessive, about 100 nosological entities. In addition, episodic cerebellar ataxia is also classified as an autosomal dominant ataxia. Among autosomal dominant ataxias, SCA3 or Machado-Joseph disease is the most common, followed by SCA2 and SCA6. However, in Russia, the prevalence is different. Among autosomal recessive ataxias, the most common is Friedreich’s ataxia, which also belongs to polyglutamine diseases. It should be taken into account that different methodological approaches lead to great heterogeneity and scattering of results in determining the prevalence of one or another form of hereditary ataxia both within the country and among the countries. The review presents current data on the prevalence of various forms of HCA in different regions of the world and populations. However, there is still a great deal of uncertainty regarding the overall prevalence of certain hereditary forms of cerebellar ataxia.

Вackground. Coronavirus (COVID-19) infection caused by SARS-CoV-2 virus is associated with a wide spectrum of clinical respiratory syndromes ranging from mild upper respiratory tract symptoms to progressive viral pneumonia and systemic multinflammatory syndrome, as well as endothelial dysfunction and thrombotic complications. Despite the decline of the pandemic, the problem of the prolonged course of SARS-CoV-2 remains relevant. Aim of the study. To present a clinical case of Sars-Cov-2 long infection with development of severe lung and myocardial damage with negative results of PCR-analysis of pharyngeal and nasal swabs. Characteristics of patients and methods of research. A clinical case demonstrating a variant of prolonged course of coronavirus infection accompanied by the development of pneumonitis and myocarditis is presented in this work. Blood smear morphometry, monocyte analysis (flow cytometry), T lymphocyte analysis were performed in addition to standard methods of examination. Results and Conclusion. The presented clinical case demonstrates a variant of prolonged course of coronavirus infection, in which SARS-CoV-2 virus was encapsulated in the lungs and avoided the formation of a specific immune response. Severe lung and myocardial damage with negative results of PCR analysis of pharyngeal and nasal swabs was observed. Pulse therapy with corticosteroids resulted in regression of the disease.

Вackground. Heart failure (HF) is one of the main causes of morbidity and mortality worldwide. Since it is important to diagnose CH early and quickly, at the outpatient appointment, there is a need to create and introduce into practice a portable highly sensitive method for the determination of BNP, NT-proBNP. Purpose of the study. To determine the possibility of using reagents for semi-quantitative determination of N-terminal brain natriuretic peptide antigen for early detection of heart failure. Methods of statistical analysis. Microsoft Office Excel 2019 program was used. Patient Characterization and Research Methods. An open cross-sectional non-randomized cohort study included 50 patients (mean age 63.5 years) who applied on an outpatient basis for consultation to a cardiologist. In addition to standard clinical, biochemical and instrumental examinations, the concentration of N-terminal brain natriuretic peptide (NT-proBNP) was determined by quantitative and semi-quantitative immunochromatographic method (LLC NPO "BioTest", Novosibirsk). The diagnosis of chronic heart failure (CHF) was established in accordance with national and European recommendations. Methods of statistical analysis. Microsoft Office Excel 2019 program was used. Results and conclusion. In the course of the study, it was found that semi-quantitative method is highly sensitive for detection of small NT-proBNP elevations, which is important for early diagnosis of heart failure, including subclinical forms. Semi-quantitative method also allows to distinguish a group of patients with high NT-proBNP values. The relationship of NT-proBNP level with the course and prognosis of CHF requires further study.

Progressive or accelerated atherosclerosis is accompanied by unfavorable clinical outcomes. Studying and understanding this process and creating a personalized method for assessing the risk and prognosis of this disease are necessary to optimize approaches to treatment and prevention. Aim: To compare two approaches to the creation of prognostic risk model of progressive atherosclerosis: non-linear regression model of logistic type and free cross-platform visual programming system Orange method. Material and Methods. The retrospective cohort study included 202 patients with confirmed coronary heart disease: 147 men and 55 women. The mean age of the patients was 53.3 ± 7.16 years. Group 1 included patients with myocardial infarction or unstable stenocardia, emergency arterial stenting, stroke, peripheral arterial thrombosis, critical ischemia and lower extremity amputation within 2 years before inclusion in the study. Patients in the comparison group did not have these events. Predictive models of the influence of different studied parameters on the probability of rapid progression of atherosclerosis were built using factor and correlation analysis and free cross-platform Orange visual programming system. Results. The authors’ suggested approaches to the evaluation of the risk of progressive atherosclerosis have a good prognostic accuracy (sensitivity 94.1, specificity 97.0 and accuracy 95.5 coefficients, respectively) for the regression model and 0,950 (95,0%) for the machine learning model. However, the construction of the regression model is a more complex procedure compared to the second approach, where the choice of informative indicators for the prediction model is made by Orange. Nevertheless, the above two approaches can successfully complement each other, allowing to build more accurate predictive risk models. Conclusion. The proposed authors’ approaches to assessing the risk of progressive atherosclerosis have a good prognostic accuracy.

The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.3, the CETP gene, and the APOE gene. In total, 2286 randomly selected patients were included. Rs708272 and rs429358 and rs7412 were analyzed using RT-PCR via the TaqMan principle, and rs1333049 vas analyzed via a commercial KASP assay. In our sample, the frequencies of alleles and genotypes were consistent with frequencies in comparable populations of Eastern and Western Europe. Allele C of rs1333049 was significantly associated with MI among males (p = 0.027) and in the whole study sample (p = 0.008). We also revealed a significant association of the ɛ2/ɛ4 genotype of APOE with MI among males (p < 0.0001) and in the whole study sample (p < 0.0001). Thus, among the tested polymorphisms, some genotypes of rs1333049 and rs429358 and rs7412 are the most strongly associated with MI and can be recommended for inclusion into a genetic risk score.

Ложкина Наталья Геннадьевна Пархоменко Ольга Михайловна Максимов Владимир НиколаевичВоевода Михаил Иванович Бравве Юрий

During differential diagnosis of diabetes mellitus, the greatest difficulties are encountered with young patients because various types of diabetes can manifest themselves in this age group (type 1, type 2, and monogenic types of diabetes mellitus, including maturity-onset diabetes of the young (MODY)). The MODY phenotype is associated with gene mutations leading to pancreatic-β-cell dysfunction. Using next-generation sequencing technology, targeted sequencing of coding regions and adjacent splicing sites of MODY-associated genes (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1) was carried out in 285 probands. Previously reported missense variants c.970G>A (p.Val324Met) and c.1562G>A (p.Arg521Gln) in the ABCC8 gene were found once each in different probands. Variant c.1562G>A (p.Arg521Gln) in ABCC8 was detected in a compound heterozygous state with a pathogenic variant of the HNF1A gene in a diabetes patient and his mother. Novel frameshift mutation c.4609_4610insC (p.His1537ProfsTer22) in this gene was found in one patient. All these variants were detected in available family members of the patients and cosegregated with diabetes mellitus. Thus, next-generation sequencing of MODY-associated genes is an important step in the diagnosis of rare MODY subtypes.

We explored the relationship between the copy number of mitochondrial DNA (mtDNA-CN) and all-cause natural mortality. We examined a random population sample in 2003/2005 (n = 9360, men/women, 45-69, the HAPIEE project) and followed up for 15 years. Using a nested case-control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer (n = 371), and a sex- and age-stratified control (n = 785). The odds ratios (ORs) of death were 1.06 (95%CI 1.01-1.11) per one-decile decrease in mtDNA-CN independent of age, sex, metabolic factors, smoking, alcohol intake and education. The age-sex-adjusted ORs of death in the second and first tertiles of mtDNA-CN vs. the top tertile were 2.35 (95% CI 1.70-3.26) and 1.59 (1.16-2.17); an increased risk was confined to the second tertile after controlling for smoking and metabolic factors. The multivariable-adjusted OR of CVD death was 1.92 (95% CI 1.18-3.15) in tertile 2 vs. the top tertile of mtDNA-CN, and for cancer-related death the ORs were 3.66 (95% CI 2.21-6.05) and 2.29 (95% CI 1.43-3.68) in tertiles 2 and 1 vs. the top tertile. In the Siberian population cohort, the mtDNA-CN was an inverse predictor of the 15-year risk of natural mortality, due to the greatest impact of CVD and cancer-related death. The findings merit attention for exploring further the role of mtDNA in human ageing and the diversity of mortality.