BackgroundThe molecular mechanisms that determine the organism's response to a variety of doses and modalities of stress factors are not well understood.ResultsWe studied effects of ionizing radiation (144, 360 and 864 Gy), entomopathogenic fungus (10 and 100 CFU), starvation (16 h), and cold shock (+4, 0 and -4°C) on an organism's viability indicators (survival and locomotor activity) and transcriptome changes in the Drosophila melanogaster model. All stress factors but cold shock resulted in a decrease of lifespan proportional to the dose of treatment. However, stress-factors affected locomotor activity without correlation with lifespan. Our data revealed both significant similarities and differences in differential gene expression and the activity of biological processes under the influence of stress factors.ConclusionsStudied doses of stress treatments deleteriously affect the organism's viability and lead to different changes of both general and specific cellular stress response mechanisms.

SummaryLifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life‐history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer‐lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing. Interestingly, these gene expression patterns resembled those of flies under dietary restriction and several other lifespan‐extending interventions, although on the individual gene level, there was no significant overlap with genes previously reported to have lifespan‐extension effects. We experimentally tested the lifespan regulation potential of several candidate genes and found no consistent effects, suggesting that individual genes generally do not explain the observed longevity patterns. Instead, it appears that lifespan regulation across species is modulated by complex relationships at the system level represented by global gene expression.

Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.

The E ( z ) histone methyltransferase heterozygous mutation in Drosophila is known to increase lifespan and stress resistance. However, the longevity mechanisms of E ( z ) mutants have not been revealed. Using genome-wide transcriptome analysis, we demonstrated that lifespan extension, increase of resistance to hyperthermia, oxidative stress and endoplasmic reticulum stress, and fecundity enhancement in E ( z ) heterozygous mutants are accompanied by changes in the expression level of 239 genes (p < 0.05). Our results demonstrated sex-specific effects of E ( z ) mutation on gene expression, which, however, did not lead to differences in lifespan extension in both sexes. We observed that a mutation in an E ( z ) gene leads to perturbations in gene expression, most of which participates in metabolism, such as Carbohydrate metabolism, Lipid metabolism, Drug metabolism, Nucleotide metabolism. Age-dependent changes in the expression of genes involved in pathways related to immune response, cell cycle, and ribosome biogenesis were found.

BackgroundWe have previously showed that the carotenoid fucoxanthin can increase the lifespan in Drosophila melanogaster and Caenorhabditis elegans. However, the molecular mechanisms of the geroprotective effect of fucoxanthin have not been studied so far.ResultsHere, we studied the effects of fucoxanthin on the Drosophila aging process at the molecular and the whole organism levels. At the organismal level, fucoxanthin increased the median lifespan and had a positive effect on fecundity, fertility, intestinal barrier function, and nighttime sleep. Transcriptome analysis revealed 57 differentially expressed genes involved in 17 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Among the most represented molecular pathways induced by fucoxanthin, a significant portion is related to longevity, including MAPK, mTOR, Wnt, Notch, and Hippo signaling pathways, autophagy, translation, glycolysis, oxidative phosphorylation, apoptosis, immune response, neurogenesis, sleep, and response to DNA damage.ConclusionsLife-extending effects of fucoxanthin are associated with differential expression of longevity-associated genes.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4471-x) contains supplementary material, which is available to authorized users.

The modulation of longevity genes and aging-associated signaling pathways using pharmacological agents is one of the potential ways to prolong the lifespan and increase the vitality of an organism. Phytochemicals flavonoids and non-steroidal anti-inflammatory drugs have a large potential as geroprotectors. The goal of the present study was to investigate the effects of long-term and short-term consumption of quercetin, (-)-epicatechin, and ibuprofen on the lifespan, resistance to stress factors (paraquat, hyperthermia, γ-radiation, and starvation), as well as age-dependent physiological parameters (locomotor activity and fecundity) of Drosophila melanogaster. The long-term treatment with quercetin and (-)-epicatechin didn't change or decreased the lifespan of males and females. In contrast, the short-term treatment with flavonoids had a beneficial effect and stimulated the resistance to paraquat and acute γ-irradiation. The short-term ibuprofen consumption had a positive effect on the lifespan of females when it was carried out at the middle age (30–40 days), and to the survival of flies under conditions of oxidative and genotoxic stresses. However, it didn't change the lifespan of males and females after the treatment during first 10 days of an imago life. Additionally, quercetin, (-)-epicatechin, and ibuprofen decreased the spontaneous locomotor activity of males, but had no effect of stimulated the physical activity and fecundity of females. Revealed quercetin, (-)-epicatechin, and ibuprofen activity can be associated with the stimulation of stress response mechanisms through the activation of pro-longevity pathways, or the induction of hormesis.

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Recent experimental studies highlighted the role of hydrogen sulfide (H2S) in aging and longevity. The cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are the key enzymes responsible for H2S production. Here we investigated the geroprotective effects of CSE and CBS overexpression in Drosophila. Overexpression of CSE did not affect a lifespan and decrease (mitochondrial form of CSE) or increase (cytoplasmic form of CSE) age dynamics of locomotor activity, while overexpression of CBS increase median (by 12.5%) and maximum (by 6.9%) lifespan and locomotor activity. Increasing of both CSE and CBS expression levels resulted in thermotolerance, but the resistance to combination of arid and food-free conditions decreased. The resistance to oxidative stress (paraquat) was not affected in flies with overexpression of CBS and cytoplasmic CSE, but decreased in flies overexpressing mitochondrial form of CSE. Thus, transgene overexpression of the CSE and CBS in Drosophila induce similar effects on stress-resistance and locomotor activity, however lifespan extending effect was revealed for CBS overexpression only.