The allele and genotype frequency distribution at polymorphic loci rs3892097 (184G>A) of CYP2D6 gene, rs776746 (6986A>G) of the CYP3A5 gene and rs2740574 (-392A>G) of the CYP3A4 gene in Russians, Tatars, and Bashkirs was examined. Samples were taken from residents of Bashkortostan Republic (1240 men and women aged from 20 to 109 years and consisted of 443 Russians, 517 Tatars, and 280 Bash kirs). Allele identification was conducted using PCR RFLP or PCR with TaqMan probes. The "nonfunc tional" allele rs3892097*A of the CYP2D6 gene was detected in populations of Russians, Tatars, and Bashkirs in 17.2, 9.5, and 7.1% cases, respectively.The rs776746*G allele of the CYP3A5 gene encoding the CYP3A5 isoenzyme with decreased activity was revealed with a frequency of 94.6% in populations of Russians, 94.3% in the Tatar population, and 91.5% in the Bashkir population. The share of the minor allele rs2740574*G of the CYP3A4 was 4.0% in populations of Russians, 0.5% in the Tatar population, and 0.9% in the Bashkir pop ulation. It has been previously shown that the rs3892097*A, rs776746*G, and rs2740574*G allele frequencies vary significantly in different world populations. Since allele variants of CYP2D6, CYP3A5, and CYP3A4 genes can play essential role in interindividual and in interethnic differences in the metabolism of many therapeutic agents, the obtained results could be used in the prognosis of pharmacotherapy efficacy in populations of Russians, Tatars, and Bashkirs.

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Nowadays over the world absolute and relative number of aging population dramatically increases with life expectancy up and birth rate down. Aging and senescence assessment are assumed to reflect current changes, internal degeneration and various stressors respond ability (i.e. genetic, environmental and occupational factors) of human organism. Occupational experience time is leading risk factor and indicator for accelerated aging. Last years, many reports concerning aging rate dependence on physical and chemical occupational hazardous factors were published. Summarizing this exposures and their effects on aging reviews are almost absent despite many provided studies. Overview of main occupational neuropsychiatric, physical and chemical risk factors, that causes human aging acceleration presented here. Circadian rhythm disorders, allostatic load, heat stress, local vibration, chemical effects and suspended nanoparticles (fine dust) influences on aging and such signs as Alzheimer’s disease risk increase, telomere length decrease and epigenetic changes and possible interactions between them are also briefly presented. Agricultural, industrial workers, teachers and police officers aging acceleration is detected in results of analysis of biological age markers.

Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of ACE*Ya5ACE, CDH4*Yb8NBC516, COL13A1*Ya5ac1986, HECW1*Ya5NBC182, LAMA2*Ya5-MLS19, PLAT*TPA25, PKHD1L1*Yb8AC702, SEMA6A*Yb8NBC597, STK38L*Ya5ac2145 and TEAD1*Ya5ac2013 Alu elements to longevity. The study group included 2054 unrelated individuals aged from 18 to 113 years who are ethnic Tatars from Russia. We analyzed the dynamics of the allele and genotype frequencies of the studied Alu polymorphic loci in the age groups of young (18–44 years old), middle-aged (45–59 years old), elderly (60–74 years old), old seniors (75–89 years old) and long-livers (90–113 years old). Most significant changes in allele and genotype frequencies were observed between the long-livers and other groups. The search for polygenic predictors of longevity was performed using the APSampler program. Attaining longevity was associated with the combinations LAMA2*ID + CDH4*D (OR = 2.23, PBonf = 1.90 × 10−2) and CDH4*DD + LAMA2*ID + HECW1*D (OR = 4.58, PBonf = 9.00 × 10−3) among persons aged between 18 and 89 years, LAMA2*ID + CDH4*D + SEMA6A*I for individuals below 75 years of age (OR = 3.13, PBonf = 2.00 × 10−2), LAMA2*ID + HECW1*I for elderly people aged 60 and older (OR = 3.13, PBonf = 2.00 × 10−2) and CDH4*DD + LAMA2*D + HECW1*D (OR = 4.21, PBonf = 2.60 × 10−2) and CDH4*DD + LAMA2*D + ACE*I (OR = 3.68, PBonf = 1.90 × 10−2) among old seniors (75–89 years old). The key elements of combinations associated with longevity were the deletion alleles of CDH4 and LAMA2 genes. Our results point to the significance for human longevity of the Alu polymorphic loci in CDH4, LAMA2, HECW1, SEMA6A and ACE genes, involved in the integration systems.

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Согласно одной из современных концепций старения и долголетия человека, причиной деградации эндогенных процессов является повышение нестабильности генома с возрастом. К факторам генетической нестабильности относятся транспозоны, или мобильные генетические элементы. В геноме человека широко распространены Alu-ретротранспозоны. Среди членов данного семейства AluYa5 и AluYb8 являются единственными, сохранившими транспозиционную активность. С целью проверки гипотезы о роли активности транспозонов AluYa5 и AluYb8 в старении и долголетии человека проведен сравнительный анализ уровня их экспрессии среди лиц разного возраста. В исследовании приняли участие 75 здоровых жителей Республики Башкортостан в возрасте от 21 до 97 лет. Общая выборка дифференцирована на возрастные группы: среднюю (38 человек, 21-39 лет), старческую (23 человека, 82-89 лет) и группу долгожителей (14 человек, 90-97 лет). Образцы РНК выделяли из лейкоцитов периферической венозной крови стандартным тризольным методом. Количественный анализ содержания AluYa5-РНК и AluYb8-РНК в лейкоцитах крови проводили методом ПЦР в реальном времени. Относительное количество мРНК определяли с помощью ΔΔCt-метода. Сравнение возрастных групп проводили с использованием однофакторного дисперсионного анализа Краскела-Уоллиса. В общей анализируемой выборке показатели относительного уровня экспрессии субсемейств AluYa5 и AluYb8 составили 0,84 и 0,80 отн. ед. соответственно. Согласно сравнительному анализу относительного уровня AluYa5-РНК и AluYb8-РНК в лейкоцитах крови людей, относящихся к трем возрастным группам, не наблюдается статистически значимых различий в экспрессии транспозонов семейств AluYa5 (Н=3,59, p=0,17) и AluYb8 (Н=2,65, p=0,27). После объединения групп лиц старческого возраста и долгожителей и сравнения их с лицами среднего возраста различия в показателях значений медианы также не достигли уровня статистической значимости (p=0,1). При этом у людей в возрасте 82 лет и старше наблюдается более низкий уровень экспрессии Alu-элементов субсемейства AluYa5 (0,75 против 2,69 отн. ед.) и AluYb8 (0,73 против 2,15 отн. ед.). Таким образом, в исследованной выборке не было обнаружено статистически значимых изменений относительного уровня экспрессии субсемейств AluYa5 и AluYb8 с возрастом. According to one of the modern concepts of human aging and longevity, the cause of the degradation of endogenous processes is the increased genome instability with age. Factors of genetic instability include transposons, or mobile genetic elements. Alu-retrotransposons are ubiquitous in the human genome. Among the members of this family, AluYa5 and AluYb8 are the only ones that retained transpositional activity. To test the hypothesis about the role of of AluYa5 and AluYb8 transposons activity in human aging and longevity, we performed the comparative analysis of their expression level among individuals of different ages. The study group included 75 healthy residents of the Republic of Bashkortostan aged between 21 and 97 years. The total sample was divided into the following groups according to age: middle-aged (38 people, 21-39 years old), elderly (23 people, 82-89 years old) and a group of long-livers (14 people, 90-97 years old). RNA samples were isolated from leukocytes of peripheral venous blood by the standard method using Trizol reagent. Quantitative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes was performed by real-time PCR. The relative amount of mRNA was determined using the ΔΔCt method. Comparison of age groups was carried out using one-way analysis of variance with the Kruskal-Wallis test. In the total analyzed sample, the expression levels of AluYa5 and AluYb8 were 0.84 and 0.80 rel. units respectively. According to the results of comparative analysis of AluYa5-RNA and AluYb8-RNA in blood leukocytes of people from three age groups, there were no statistically significant differences in the expression of AluYa5 (H = 3.59, p = 0.17) and AluYb8 (H = 2.65, p = 0.27). After combining the groups of elderly people and long-livers and comparing them with middle-aged people, the differences in the median values also did not reach the level of statistical significance (p = 0.1). At the same time, people aged 82 and older demonstrated lower level of expression of AluYa5 subfamily (0.75 versus 2.69 rel. units) and AluYb8 subfamily (0.73 versus 2.15 rel. units). There were no statistically significant changes in the relative expression level of the AluYa5 and AluYb8 subfamilies with age in the study group.