RESUMEN
Gene expression is much altered in aging. We observed age-dependent decline of core clock genes' expression in the whole body of the fruit fly. We hypothesized that inducible overexpression of clock genes (cry, per, tim, cyc and Clk) in the nervous system can improve healthspan of D. melanogaster. We studied the lifespan of transgenic Drosophila and showed life extension for cry, per, cyc and tim genes. It was also the significant positive changes in the stress-resistance of flies overexpressing core clock genes in conditions of hyperthermia, hyperoxia, starvation and persistent lighting. The overexpression of per and cry restore circadian rhythms of locomotor activity. The results presented support the hypotheses that the compensation of circadian oscillator genes expression can improve the healthspan in Drosophila melanogaster.
Asunto(s)
Proteínas CLOCK/biosíntesis , Proteínas de Drosophila/biosíntesis , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulación de la Expresión Génica/fisiología , Longevidad/genética , Neuronas/metabolismo , Envejecimiento/genética , Envejecimiento/fisiología , Animales , Animales Modificados Genéticamente , Proteínas CLOCK/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiología , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Femenino , Fiebre/genética , Fiebre/fisiopatología , Locomoción/genética , Locomoción/fisiología , Longevidad/fisiología , Masculino , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Estimulación Luminosa , Inanición/genética , Inanición/fisiopatologíaRESUMEN
BACKGROUND: We 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. RESULTS: Here, 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. CONCLUSIONS: Life-extending effects of fucoxanthin are associated with differential expression of longevity-associated genes.
Asunto(s)
Perfilación de la Expresión Génica , Longevidad/genética , Xantófilas/metabolismo , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiología , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Femenino , Fertilidad/genética , Mucosa Intestinal/metabolismo , Locomoción/genética , Masculino , Estrés Oxidativo/genética , PermeabilidadRESUMEN
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.
RESUMEN
BACKGROUND: The molecular mechanisms that determine the organism's response to a variety of doses and modalities of stress factors are not well understood. RESULTS: We 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. CONCLUSIONS: Studied doses of stress treatments deleteriously affect the organism's viability and lead to different changes of both general and specific cellular stress response mechanisms.