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.

[THE EFFECT OF DIETARY RESTRICTION DURING DEVELOPMENT OF DROSOPHILA MELANOGASTER ON THE ACTIVITY OF ANTIOXIDANT SYSTEM ENZYMES].

In the previous study we demonstrated that dietary restriction only at the development stage of Drosophila melanogaster may impact the life span of adult flies. It was important that we didn't use qualitative (restriction of proteins or other macro- or microelements) and not a calorie restriction as well, but quantitative dietary restriction that was the proportional reduction of all food components in the larval medium. In the situations when the larvae were reared in the medium types, that contained protein and carbohydrate components in concentrations of 90-10% of food components compared to the standard one (100%), the males were characterised with the significant increase in the maximum life span. The average life span was also increased, but only in those male individuals that developed in the medium types, that contained 50% and 60% of food components compared to controls. Such an effect we haven't detected in the female flies. To study the biochemical changes associated with the physiological effects we have determined the activity of the antioxidant enzymes--superoxide dismutase (SOD) and catalase. In the male flies the 50% dietary restriction implemented during the development has led to the significant increase in a SOD and catalase activity. Also the flies of both sexes reared in the medium with the 50% of food components have been characterised with the reduction in the accumulation of glycation end products. According to these results, we suggest that the changes in the activity of antioxidant enzymes may play a role in the increase of the flies life span caused by the dietary restriction during the development.

[The study of telomere length in patients with Parkinson's disease].

OBJECTIVE: Telomeres which are formed by double-strand breaks and DNA under replication, cause cell cycle arrest resulting in cellular senescence and apoptosis. The erosion of telomeres is an important mechanism for regulating the aging process by limiting cell proliferation. Over the last decade, many investigations in the field of telomeric biology showed that telomeric DNA and telomeric proteins are involved in the pathogenesis of some human diseases. The aim of the study was to compare telomere length in patients with Parkinson's disease (PD). MATERIAL AND METHODS: Telomere length was measured in buccal epithelial cells and leukocytes in PD patients and controls. RESULTS AND CONCLUSION: The length of telomeres in cells of buccal epithelium was shorter in patients with PD than in the control group. In blood cells, telomere length did not differ. It is suggested that shortening of telomeres in buccal epithelial cells may be due to oxidative stress and, hence, it can be used as a marker for the early stages of disease.

[Effect of valproic acid on SMN protein level in peripheral blood mononuclear cells of patients with spinal muscular atrophy and different SMN2 copy numbers].

OBJECTIVE: Spinal muscular atrophy (SMA) is currently untreatable hereditary disorder caused by few types of mutations in the SMN1 gene and respective lack of gene's product - survival motor neuron protein (SMN). Last decade studies have shown that phenotype of the disorder is substantially influenced by copy numbers of homologous SMN2 gene; also, an ability of valproic acid to increase the level of SMN in vitro and in vivo has been shown. We investigated an effect of valproic acid on SMN level in peripheral blood mononuclear cells derived from patients with SMA and their parents and sought for possible predictors for treatment efficacy. MATERIAL AND METHODS: We examined 10 children with SMA and 6 their parents as heterozygous carriers of the mutation using appropriate molecular-genetic techniques. Valproic acid was prescribed in 20mg/kg/day during 2 weeks. RESULTS AND CONCLUSION: There were no correlation between baseline SMN level and SMN2 copy number; both of the markers do not predict SMN level after the treatment with valproic acid. However, all of patients responded to valproic acid treatment with different grades of SMN level increase. Strong intrafamilial correlation was found for the SMN/Β2-microglobulin ratio.

[Effect of dietary restriction during development on the level of expression of longevity-associated genes in Drosophila melanogaster].

It is well known that dietary restriction (DR) may substantially affect the life span (LS) of various model organisms including Drosophila melanogaster. In our recent studies, it has been revealed that the reduction of the content of main nutrients in larval medium may lead to an increase of flies' LS. Analysis of these data suggested that the most likely candidate for such long-term adaptive changes is insects' epigenome (i.e., persistent changes in the activity of genes that are not related to changes in the DNA structure). To examine whether the observed effects may be associated with long-term changes in the epigenetic regulation of genes associated with aging and longevity, in the present study we determined the level of expression of InR and Sir2 genes that are related to the effects of DR. In the larvae developed in DR conditions, the significant increase in the level of transcription of both these genes compared to the controls has been detected. The adult males have shown a significant increase in the level of expression of InR gene while no such changes were observed in females. The Sir2 gene expression level was not different from the control level in adults of both sexes. It has been suggested that larval nutritional stress may lead to the induction of adaptive epigenetic rearrangements and, therefore, it can extend the flies' longevity.

[Effect of the histone deacetylase inhibitor sodium butyrate on the viability and life span in Drosophila melanogaster].

Histone acetylation (one of the most important epigenetic mechanisms controlling gene expression) has been recently shown to be involved in life span (LS) determination. There are some data indicating the geroprotective potential of histone deacetylase (HDAC) inhibitors. In the present study, the effects of HDAC inhibitor, sodium butyrate (SB), on the parameters of viability and LS of Drosophila melanogaster were studied. Since SB is an efficient inducer of epigenetic changes, it can be assumed that its use as a life-extending agent (geroprotector) can be quite promising.

[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.