Larval crowding results in hormesis-like effects on longevity in Drosophila: timing of eclosion as a model.

There is increasing evidence that stress during development can affect adult-life health status and longevity. In the present study, we examined life span (LS), fly weight, fecundity and expression levels of longevity-associated genes (Hsp70, InR, dSir2, dTOR and dFOXO) in adult Drosophila melanogaster flies reared in normal [low density (LD), ~ 300-400 eggs per jar] or crowded [high density (HD), more than 3000 eggs per jar] conditions by using the order (day) of emergence as an index of the developmental duration (HD1-5 groups). Developmental time showed a significant trend to increase while weight showed a significant trend to decrease with increasing the timing of emergence. In both males and females eclosed during first 2 days in HD conditions (HD1 and HD2 groups), both mean and maximum LSs were significantly increased in comparison to LD group. In males, mean LS was increased by 24.0% and 23.5% in HD1 and HD2 groups, respectively. In females, corresponding increments in mean LS were 23.8% (HD1 group) and 29.3% (HD2 group). In HD groups, a strong negative association with developmental time has been found for both male and female mean and male maximum LSs; no association with growth rate was observed for female maximum LS. The female reproductive activity (fecundity) tended to decrease with subsequent days of eclosion. In HD groups, the levels of expression of all studied longevity-associated genes tended to increase with the timing of eclosion in males; no differences were observed in females. On the basis of findings obtained, it can be assumed that the development in conditions of larval overpopulation (if not too extended) could trigger hormetic response thereby extending the longevity. Further studies are, however, needed to confirm this assumption.

Reciprocal cross differences in Drosophila melanogaster longevity: an evidence for non-genomic effects in heterosis phenomenon?

Reciprocal cross effects (i.e., differences between reciprocal hybrids that are developed by reversing the strains from which the dam and the sire are taken) are commonly used as a measure of sex-linkage or maternal effects. However, the papers reporting parental effects on life span of experimental animals are scarce. In order to investigate the potential of parent-of-origin effects for the longevity of hybrids, we determined the life spans of the inbred lines of Drosophila melanogaster [Oregon-R (OR), Canton-S (CS) and Uman (Um)] that differ significantly in longevity, as well as the life span of the progeny from the reciprocal crosses among them. The hybridization caused the increase in both flies' mean and maximum life span mainly shifting the survival curves upward proportionally at all ages. This resulted in the reduction in the Gompertz intercept (frailty) whereas the Gompertz slope (the rate of aging) was predominantly unchanged. Better-parent heterosis was observed in hybrids between OR and Um inbred lines and the extent of heterosis was more pronounced in hybrids between CS and Um inbred lines if long-lived parent was used as the female parent, and short-lived parent was used as the male parent in the crossing scheme. Such discrepancy in life span between reciprocal crosses may indicate that non-chromosomal factors are significantly contributing to a heterotic response. Our data are in line with the previous reports suggesting the involvement of non-genomic factors, particularly epigenetic events attributed to hybridization, in the manifestation of heterosis.

[Ontogenetic clock: molecular-genetic mechanism].

Proposed is a hypothesis of the mechanism providing for the cell to count out the time of life and to change (according to the set program) the expression of chromosomal genes in order to control ontogenesis ("ontogenetic clock"). This mechanism represents an autonomous molecular-genetic oscillator, which memorizes the number of cycles of own oscillations through cutting the terminal tau-segment of chrono-DNA using special restrictase. The latter is formed at this segment out of two sub-units (proteins) in each cycle of oscillator operation. These proteins are alternately synthesized on ribosomes, since each inhibits the synthesis of the other, thus ensuring successive binding of restrictase sub-units at the terminal segment of chrono-DNA and its single section in one cycle. In addition, each of these proteins is a repressor of own gene and activator of the gene of the other protein, thus ensuring efficiency and reliability of oscillator operation. The design of oscillator of ontogenetic clock is similar to that of circadian oscillator, but its frequency is not synchronized with the nature's physical rhythms and depends on body temperature. Therefore, it is physical rather than biological time that is measured. The chrono-DNA consists of short repetitive sequences of nucleotides (tau-segments) and temporal (regulatory) genes inserted over specified number of these segments. The shortening of chrono-DNA leads to uncovering the next gene and to its destruction by exonuclease. As a result, the synthesis of activator (repressor) stops and the expression of some chromosomal genes changes, initiating the next stage of ontogenesis.

[Predisposition to type II diabetes in Ukraine residents exposed to famine 1932-1933 during prenatal development].

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 effect of pH and pO2 changes in the blood on the energy metabolism of human erythrocytes in old age]. / Vliianie izmenenii pH i pO2 krovi na énergeticheskii obmen éritrotsitov cheloveka v starosti.

Changes in pH and pO2 of the blood have been studied for age peculiarities of their effect on the glycolysis rate and the content of ATP and 2,3-diphosphoglycerate (2,3-DPG) in erythrocytes (in vitro). The fresh venous blood of practically healthy young (aged 20-29) and old (aged 75-85) people was used. Acidosis was shown to induce inhibition of glycolysis and decrease of the ATP and 2.3-DPG concentrations in erythrocytes, while alkalosis and hypoxemia-an increase of the glycolysis rate and 2.3-DPG content. In the both cases changes in the indices studied were considerably lower in old people as compared to young ones.

[The oxygen transport function and energy metabolism of erythrocytes in human aging]. / Sauerstofftransportfunktion und Energieumsatz von Erythrozyten beim Altern des Menschen.

Age-related changes of hemoglobin affinity to oxygen and intraerythrocyte factors which determine it (pH, pCO2, rate of glycolysis, content of organic phosphates) were studied. The results obtained showed the decrease in aging of the affinity of hemoglobin to oxygen resultant from the decrease of pH of intraerythrocyte medium (Bohr effect), despite the inhibited energy metabolism and decreased content of organic phosphates in erythrocytes.

[Mechanism of changes in the rate of glycolysis and levels of ATP and 2,3-diphosphoglycerate in human erythrocytes during aging]. / O mekhanizme izmeneniia skorosti glikoliza i soderzhaniia ATP i 2,3-difosfoglitserata v éritrotsitakh cheloveka pri starenii.

Reasons which have induced changes in the glycolysis rate, ATP and 2,3-diphosphoglycerate content in human erythrocytes with ageing are studied. A fall of the hexokinase activity is shown to be one of the reasons of a significant decrease in the glycolysis rate. The total ATPase activity in erythrocytes does not change with the age. At the same time the decay rate of 2,3-diphosphoglycerate increases, that, evidently, is one of the reasons of the 2,3-diphosphoglycerate content decrease in erythrocytes with ageing.

[Mechanisms of the effect of propranolol on the oxygen transport function of the blood in elderly patients with ischemic heart disease]. / O mekhanizmakh vliianiia propranolola na kislorodtransportnuiu funktsiiu krovi u bol'nykh ishemicheskoi bolezn'iu serdtsa pozhilogo vozrasta.

In vivo effects of varying concentrations of propranolol on the oxyhemoglobin dissociation curve, and its in vitro effects on erythrocyte energy metabolism were studied in 12 elderly and old coronary patients. An 80 mg oral dose of propranolol evoked a significant shift to the right in the oxyhemoglobin dissociation curve due to a decrease in blood pH (Bohr's effect) and, according to in vitro evidence, the release of membrane-bound ATP and 2,3-diphosphoglycerate. As a result, propranolol improved blood oxygen release in tissue capillaries, as evidenced by elevated pO2 in subcutaneous fat.

[Age-related changes in glycolysis and levels of modulators of oxygen transport function of hemoglobin in human erythrocytes]. / Vozrastnye izmeneniia glikoliza i soderzhaniia moduliatorov kislorodtransportnoi funktsii gemoglobina v éritrotsitakh cheloveka.

The glycolysis rate and the amount of the acid-transport hemoglobin function modulators (diphosphoglycerate (2,3-DPG), ATP, glutathione, chlorides) in human erythrocytes are studied under the effect of age changes. It is shown that the glycolysis rate and the content of ATP decrease under ageing by 16% and 21%, respectively. The concentration of 2,3-DPG lowers insignificantly (by 8%). At the same time it is established that the amount of reduced glutathione in erythrocytes of middle-aged and old people enhances by 25-29% and that of chlorine ions by 23-24%. The revealed changes in the concentration of modulators of the hemoglobin affinity to oxygen with ageing are, probably, one of reasons of the oxyhemoglobin dissociation increase.