Current recommendations for limiting exposure to ionizing radiation are based on the linear no-threshold (LNT) model for radiation carcinogenesis under which every dose, no matter how low, bears some cancer risk. In this review, epidemiological evidence is discussed that the LNT hypothesis is incorrect at low doses. A large set of data was accumulated that show that cancer risk after ordinarily encountered radiation exposure (natural background radiation, medical X-rays, etc.) is much lower than estimates based on the LNT model. The discovery of low-level radiation hormesis (stimulating effect) implies a non-linear dose-response curve in the low-dosage region. Further studies in this field will provide new insights into the mechanisms of radiation carcinogenesis.

Many studies have shown that organism is mostly sensitive to different influences in pre- and postnatal periods of ontogenesis. During the critical periods of development, these influences induce changes in the organism that relate to ontogenetic plasticity and lead to permanent changes in structure and function of different organs and systems of the organism. It is suggested that the main molecular mechanisms of so-called “ontogenetic programming” are based on changes that occur on the epigenetic level, including changes in the genetic expression not connected with modifications of DNA structure. The present review deals with experimental and epidemiologic evidences of the role of epigenetic processes in aging and determination of susceptibility to some age-related diseases, such as cancer, cardiovascular and neurodegenerative diseases, and insulin-independent diabetes.

It has been shown in a series of works that famine experienced in early ontogenesis may have remote consequences for human health. The present study contains an analysis of the prevalence of type II diabetes (T2DM) among those of Ukraine’s residents who were born during the famine of 1932–1933, as well as before and after it. The study results have revealed a significantly higher prevalence of T2DM in individuals whose development in utero was exposed to the period of maximally expressed starvation (1933), compared to that of the subjects unexposed to the famine during their prenatal development phase. These differences were clearly manifested in the individuals born within the first half of the year and were completely absent in the subjects born in the second half, which may serve as evidence of the involvement of seasonal natural factors in the pathological processes. Our possible explanation for the above is that if a person’s development happens to be exposed to famine, this may lead to the induction of remote metabolic changes, which have an adaptive importance in early postnatal ontogenesis, but which raise the risk of T2DM developing later in life.

В большом количестве исследований показано, что организм наиболее чувствителен к различным воздействиям на протяжении периода пре- и постнатального развития. Эти воздействия приводят к тому, что изменения на протяжении критических периодов созревания, связанные с онтогенетической пластичностью, приводят к перманентным изменениям в структуре и функции определенных органов и систем организма. Предполагается, что основным молекулярным механизмом “онтогенетического программирования” являются изменения, происходящие на эпигенетическом уровне (включающие изменения в генетической экспрессии, которые возникают без изменений в структуре ДНК). В обзоре рассмотрены экспериментальные и эпидемиологические доказательства того, что эпигенетические процессы играют важную роль также на поздних этапах жизни и могут в значительной степени определять особенности старения и предрасположенность к возраст-зависимым заболеваниям, в том числе раку, кардиоваскулярным и нейродегенеративным заболеваниям, а также диабету 2 типа.

It has been shown in a number of studies that the early-life exposition to famine can have long-term consequences for human health. In the present study, the analysis of type 2 diabetes (T2D) prevalence in Ukraine residents born before, during, and after the famine 1932-1933 was performed. It has been found that T2D prevalence is increased in the people exposed to the peak of the famine during prenatal development compared with those not exposed to famine. Such differences are predominantly expressed in those persons born during the first half-year, and they are absent in those born during the second half-year thus pointing to the role of seasonal factors in driving famine-induced disease pathogenesis. We hypothesized that prenatal exposure to famine can result in induction of the long-term metabolic changes that have adaptive significance during early postnatal development but predispose to metabolic disorders at the late stages of life.

The review systematizes the evolutionary genetic approaches to the problem of aging, basing on the concepts of different reliabilities of separate biological processes and of balance between the reliabilities of these processes at a level that guarantees survival and reproduction in aggressive environment. The basic concepts of the Kirkwood’s disposable soma theory, according to which the viability potential is determined by a compromise in the allocation of the organism’s resources between reproduction and repair and maintenance of the soma are discussed. The basic concepts of the balance evolutionary genetic theory of aging are presented.

Keywords Birthcohorts.Early-lifeconditions.Month-of-birthpattern.Type2diabetesTo the Editor: Epidemiological studies have repeatedlyshown a link between poor fetal growth and increased riskof developing type 2 diabetes [1]. Month of birth is a goodinstrument for the assessment of effects of early growth onadult health independent of life-course factors. This is truebecause in decades past there were important seasonaldifferences in nutrition, especially in developing countriessuch as Ukraine. These differences in access to high-qualityfood supply can potentially influence intrauterine growth,depending on the month of gestation [2]. Other possibletriggering factors for developing type 2 diabetes, such asproduction of vitamin D [3] and outdoor temperature [4],also tend to change seasonally.Seasonal pattern of birth in type 1 diabetic children andadolescents was repeatedly described around the world,including our recent study in Ukraine [5]. In contrast, theseasonality of birth in type 2 diabetic patients waspreviously reported only in a few small-sample studies,e.g. in 155 African-American type 2 diabetic adolescent [6]and 282 adult patients in the Netherlands [7]. To studywhether abnormal seasonality of birth exists in middle- toold-aged type 2 diabetic patients in Ukraine, we comparedthe month-of-birth patterns in type 2 diabetic patients in threelarge Ukrainian regions with those in general populations.Information on date of birth, sex and year of diagnosiswas extracted from the nationwide primary-care-basedUkrainian diabetes mellitus register created in 2000 in theInstitute of Endocrinology, Kiev, Ukraine. The definition oftype 2 diabetes was based on onset after 39 years of age,irrespective of the type of treatment.Cases were identified from the three regional diabetesregisters with high completeness of ascertainment: Cherni-giv (100%), Kherson (99.7%) and Rivne (86.2%). Theseregisters cover 7.4% of the total Ukraine population. Afemale excess was evident in all three registers. Cases wereall people alive with diagnosis of type 2 diabetes as of1 January 2008, and who were diagnosed at age 40 or later.Only people born before 1 January 1960 were included;thus all cases included were at least 48. In total, 17,510male and 34,704 female type 2 diabetic patients werefinally included in the study. Reference populations werebased on the Ukraine census 2001 depersonalised data.These populations included people who had been bornduring the same period and were residents of the sameregions: Chernigiv, 247,253 men and 369,357 women;Kherson, 208,944 men and 291,802 women; Rivne,189,887 men and 260,674 women.

Numerous epidemiological studies have shown differences in seasonality of birth patterns between the general population and the group who develop type 1 diabetes mellitus. This finding indicates that environmental factors operating during pre- and/or postnatal development could be aetiologically important. We examined whether the pattern of month of birth for type 1 diabetes patients in Ukraine differs from that for total live births.

Type 1 diabetes mellitus is a chronic disease characterized by autoimmune degradation of insulinproducing β-cells. Seasonality of birth of children with type 1 diabetes has been shown in a number of epidemiological studies. It could testify that autoimmune process began during fetal and postnatal development. No such studies were carried out in the former Soviet Union countries. The aim of the present study is to compare the seasonal birth month pattern in patients with type 1 diabetes (10780 men and 9337 women) born in 1960–2003 to that in the total population of Ukraine (14 995768 men and 14 109792 women) born during the same period. Significant differences were found between these two populations: χ 2 = 103.97, p < 0.0001 and 135.17, p < 0.0001 in men and women, respectively. The results of cosinor analysis showed similar sinusoidal birth patterns of patients with type 1 diabetes in all subgroups, irrespective of the age of clinical disease manifestation: 0–9, 10–19, or 20–29 years. In all cases, the highest and lowest predispositions to type 1 diabetes were inherent in the people born in spring and autumn, respectively. In all groups, the highest incidence rate was in persons born in spring and early summer and the lowest ones, in those born in autumn and early winter. We propose that seasonality of birth of patients with type 1 diabetes in the two above populations could be due to long-term programming of glucose-insulin metabolism caused by the effect of certain seasonal factors during early ontogenesis.

The long-term effects of the R-irradiation of D. melanogaster at the 1-hour egg stage with the dosages of 0.25, 0.50, 0.75, 1.0, 2.0 and 4.0 Gy were investigated. DNA samples were isolated from whole 5-6-days adult males. The aliquots of DNA were digested by S1-nuclease. Preimaginal stage lethality increased with irradiation dose increasing. At the same time, decrease in imaginal LS (life span) was observed after irradiation with the greatest dose (4 Gy) only. Moreover, hormesis by LS has revealed: in males irradiation with 0.25, 0.75 and 1 Gy increased the mean LS, and with 0.25 and 0.5 Gy caused the maximum LS; in females exposures with 0.25, 0.75 and 2 Gy increased the maximum LS. The densitometric assay of DNA electrophoregrams showed decrease by 39.2% of the part of high-molecular-weight DNA in control as a result of S1-nuclease action. Samples of DNA from the irradiated flies were more stable to enzyme action. The higher stability of DNA originated from the irradiated flies could be the result of reparation system activation. Ultrastructural changes induced at the egg stage by irradiation at the dose of 0.75 Gy testify the increased transcriptional activity of the brain cells.

It is supposed that longevity might be programmed by early life exposures. We had carried out demographic and experimental researches for the examination of the possibility of longevity programming. In demographic study, the recorded deaths in Kiev (Ukraine) between 1990 and 2000 (51,503 men and 50,131 women) were used. Age at death was strongly associated with month of birth. Subjects born in the middle of year (April-July) had the lowest longevity. Increasing longevity was observed with each successive birth-month in the second half of the year, with a peak longevity for births in December. To research of the mechanisms responsible for longevity programming, study of adult D. melanogaster DNA repair capacity after irradiation at the egg stage was carried out, using marker such as DNA strand breaks. Insects irradiated in low doses (0.50 and 0.75 Gy) had extended life span and increased stability to S1 nuclease treatment. The probable explanation of observed postponed effects might be the long-term modulation of certain (possibly repair) genes activity. We hypothesize that life-extending effects of different anti-aging treatments might be a consequence of their unspecific (hormetic) action, rather then specific (geroprotector) action on the some aging-related processes, and induction an "transcriptional reprogramming" may be a key mechanism of the longevity programming and artificial life extension.

Based on the factor analysis (the method of principal components with a varimax rotation of axes), a study was performed on the component structure of interpopulational variations in frequencies of the 50 phenotypes and genes of six polymorphic human systems (ABO, MNSs, Rh, Hp, Gm, HLA). The genetic differences of populations have been found to be related to a small number of independent factors; 7 principal components have extracted 79% of dispersion from the primary data. Five of these components are coupled with mortality from the cardiovascular diseases. The component structure of mortality has specificity in relation to localization of pathological process, age and sex.

The factor analysis of the osmotic erythrocyte resistance involved 380 human subjects of both sexes aged from 20 to 106 years. It has been found that body aging is accompanied by a more marked aging of the blood cells during their circulation in the blood.

A method of major components was used to develop a mathematical model which permits representing a set of parameters characterizing the process of human peripheral blood lymphocyte PhGA-blasttransformation as nine mutually independent units (components). A quantitative estimation is made for the dependence of blasttransformation parameters on the contribution of separate components which was shown to vary from 5.6 to 24.0%.