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Recently we demonstrated [1] that the dietary intake of sodium butyrate, which is a histone deacetylase inhibitor, by Drosophila melanogaster, either throughout their whole life or at the adult stage only, results in an increased life span. The potential impact of sodium butyrate on epigenetic control of gene function and, therefore, the possibility of its long-term influence on life span led to the assumption that dietary supplementation with sodium butyrate during the larval stage of development may result in a potential increase of the adult life span. Experimental verification of this hypothesis was carried out in the present study. Nutritional supplementation with sodium butyrate during the larval stage of development at a concentration of 20 mmol/L resulted in a statistically significant increase in the average life span of male flies. The maximum life span of males was statistically increased in the case of sodium butyrate intake at concentrations of 10, 20, and 40 mmol/L. The average life span in females was demonstrated to remain at a similar level following the administration of sodium butyrate, whereas the maximum life span increased significantly in a female group treated with sodium butyrate at a concentration of 10 mmol/L compared to the control group. Female reproductive activity remained the same in all groups. To test the hypothesis whether the observed long-term effect of sodium butyrate exposure on the flies’ longevity is caused by the induction of persistent epigenetic changes, the levels of expression of some longevity-associated genes, including hsp70, sir2, and InR, were determined. The expression level of sir2, which is known to play an important role in the stimulation of longevity after calorie restriction, increased significantly in a group of flies treated with sodium butyrate at a concentration of 20 mmol/L at the larval stage and further subjected to starvation in the postdevelopment stage in comparison with the control group. [ABSTRACT FROM AUTHOR]

Introduction. Substance use disorders (SUDs), including drug (DD), alcohol (AD) and nicotine (ND) dependence, are global threats for physical and mental public health. In Ukraine, ~350,000 people inject drugs, and ~6% of adult population have alcohol abuse. We may expect an increase of this problem as a consequence of war and acute social problems. SUDs are highly co-morbid with each other and there is evidence for co-morbidity with other health-related traits. This suggests underlying shared genetic effects. Aim. We investigated association of a validated in other populations GWAS-identified AD risk locus ADH1B-ADH1C rs1789891 with a range of SUDs in Ukrainians and evaluated its potential effects on other traits in GWAS summary statistics from Biobanks. Methods. We genotyped rs1789891 at ADH1B-ADH1C in a multivariate dataset including 507 individuals with and without SUDs from Ukraine (mean age 32.6±9.6 years, among them 133 individuals without any SUDs) using PCR. We performed logistic regression for DD, AD, and ND, adjusting for sex and other SUDs phenotypes. We further conducted a phenome-wide association study of rs1789891 in summary statistics from UK Biobank (UKBB) and FinnGen. Results. rs1789891 in Ukrainians was associated with AD (p = 0.0087) and DD (p = 0.0321), with the direction of effect corresponding to GWAS data, but not with ND, or alcohol consumption. rs1789891 showed an association in the UKBB with alcohol intake frequency (p = 2.45×10–24) and suggestive evidence for associations with F10 AD (p = 3.27×10 –8 ), Waist/Hip circumference ratio (p = 3.02×10–6), and Non-insulin-dependent diabetes mellitus (p = 3.03×10–6). In FinnGen, rs1789891 was significantly associated with different definitions of Alcohol use disorder (p = 1.8×10–11–1.5×10–6) and Substance abuse (p = 5.7×10–8), and there was a suggestive evidence for associations with Acute renal failure (p = 1.2×10–4), and death from Alcohol related diseases (p = 1.7×10–4). Conclusion. Variations at ADH1B-ADH1C may have pleiotropic effects on SUDs as well as some physical health traits. [ABSTRACT FROM AUTHOR]

Succinate is one of the most important raw materials in the energy-producing cycle, enabling a 'shortcut' route for ATP production via oxidative metabolism. Fumarate is produced from succinate by the oxygen-dependent succinate dehydrogenase. In this study we investigated the influence of different succinic acid concentrations on the process of cellular senescence under normal and hypoxic conditions. The most promising doses were chosen by using a cell viability test (0.2-1.5 mM). After the long-term cultivation it was shown that there was no significant difference in senescence β-galactosidase expression between samples with variable concentrations of succinate. Despite this fact, large differences in expression levels of senescence and pluripotency markers were found between the samples depending on the oxygen level and concentration of succinic acid., (© 2023 The Authors.)

Health impacts of low-dose ionizing radiation are significant in important fields such as X-ray imaging, radiation therapy, nuclear power, and others. However, all existing and potential applications are currently challenged by public concerns and regulatory restrictions. We aimed to assess the validity of the linear no-threshold (LNT) model of radiation damage, which is the basis of current regulation, and to assess the justification for this regulation. We have conducted an extensive search in PubMed. Special attention has been given to papers cited in comprehensive reviews of the United States (2006) and French (2005) Academies of Sciences and in the United Nations Scientific Committee on Atomic Radiation 2016 report. Epidemiological data provide essentially no evidence for detrimental health effects below 100 mSv, and several studies suggest beneficial (hormetic) effects. Equally significant, many studies with in vitro and in animal models demonstrate that several mechanisms initiated by low-dose radiation have beneficial effects. Overall, although probably not yet proven to be untrue, LNT has certainly not been proven to be true. At this point, taking into account the high price tag (in both economic and human terms) borne by the LNT-inspired regulation, there is little doubt that the present regulatory burden should be reduced., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

It is known that the poor nutrition during a fetal development may contribute to an increased risk of chronic diseases in adulthood. In a modern literature, this phenomenon is called «the nutritional programming of age-related pathologies». It is assumed that the qualitative or quantitative deficiency of certain nutritional components during an early development may lead to the adaptations that contribute to improved survival during the prenatal and early postnatal periods of an ontogenesis. However, the consequence of such adaptive changes may also be the development of various pathological processes at the later stages of life. Recent studies have shown that one of the major mechanisms involved in these adaptations is the epigenetic regulation of a gene activity. In this review, the experimental evidence is provided that processes arising from a quantitatively or qualitatively restricted diet during the early stages of development play an important role in the further life and can greatly influence risk of various age-related diseases and life span.

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.