Alternative NADH dehydrogenase extends lifespan and increases resistance to xenobiotics in Drosophila

Mitochondrial alternative NADH dehydrogenase (aNDH) was found to extend lifespan when expressed in the fruit fly. We have found that fruit flies expressing aNDH from Ciona intestinalis (NDX) had 17-71% lifespan prolongation on media with different protein-tocarbohydrate ratios except NDX-expressing males that had 19% shorter lifespan than controls on a high protein diet. NDX-expressing flies were more resistant to organic xenobiotics, 2,4-dichlorophenoxyacetic acid and alloxan, and inorganic toxicant potassium iodate, and partially to sodium molybdate treatments. On the other hand, NDX-expressing flies were more sensitive to catechol and sodium chromate. Enzymatic analysis showed that NDX-expressing males had higher glucose 6-phosphate dehydrogenase activity, whilst both sexes showed increased glutathione S-transferase activity.Peer reviewe

Alternative NADH dehydrogenase extends lifespan and increases resistance to xenobiotics in Drosophila (vol 147, pg 2311, 2020)

Correction to https://doi.org/10.1007/s10522-019-09849-8Peer reviewe

Insulin-Like Peptides Regulate Feeding Preference and Metabolism in Drosophila

Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) that are involved in the regulation of carbohydrate concentrations in hemolymph as well as in accumulation of storage metabolites. In the present study, we investigated diet-dependent roles of DILPs encoded by the genes dilp1–5, and dilp7 in the regulation of insect appetite, food choice, accumulation of triglycerides, glycogen, glucose, and trehalose in fruit fly bodies and carbohydrates in hemolymph. We have found that the wild type and the mutant lines demonstrate compensatory feeding for carbohydrates. However, mutants on dilp2,3, dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast diets. To evaluate metabolic differences between studied lines on different diets we applied response surface methodology. High nutrient diets led to a moderate increase in concentration of glucose in hemolymph of the wild type flies. Mutations on dilp genes changed this pattern. We have revealed that the dilp2 mutation led to a drop in glycogen levels independently on diet, lack of dilp3 led to dramatic increase in circulating trehalose and glycogen levels, especially at low protein consumption. Lack of dilp5 led to decreased levels of glycogen and triglycerides on all diets, whereas knockout on dilp7 caused increase in glycogen levels and simultaneous decrease in triglyceride levels at low protein consumption. Fruit fly appetite was influenced by dilp3 and dilp7 genes. Our data contribute to the understanding of Drosophila as a model for further studies of metabolic diseases and may serve as a guide for uncovering the evolution of metabolic regulatory pathways

Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in Drosophila

The insulin–IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in Drosophila melanogaster, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the Drosophila transcripts for the insulin-like peptides dilp2, dilp5, and dilp6. This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (tobi). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, Pten knockdown to enhance IIS also activated JAK–STAT signaling in gut tissue by up-regulation of upd2, upd3, and soc36 genes, as well as genes encoding the EGF receptor ligands spitz and vein. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival

Lifespan extension and delay of age-related functional decline caused by Rhodiola rosea depends on dietary macronutrient balance

Abstract Background This study was conducted to evaluate the effects of rhizome powder from the herb Rhodiola rosea, a traditional Western Ukraine medicinal adaptogen, on lifespan and age-related physiological functions of the fruit fly Drosophila melanogaster. Results Flies fed food supplemented with 5.0 mg/ml and 10.0 mg/ml of R. rosea rhizome powder had a 14% to 17% higher median lifespan, whereas at 30.0 mg/ml lifespan was decreased by 9% to 12%. The preparation did not decrease fly fecundity.The effect of R. rosea supplement on lifespan was dependent on diet composition. Lifespan extension by 15% to 21% was observed only for diets with protein-to-carbohydrate ratios less than 1. Lifespan extension was also dependent on total concentration of macronutrients. Thus, for the diet with 15% yeast and 15% sucrose there was no lifespan extension, while for the diet with protein-to-carbohydrate ratio 20:1 R. rosea decreased lifespan by about 10%.Flies fed Rhodiola preparation were physically more active, less sensitive to the redox-cycling compound menadione and had a longer time of heat coma onset compared with controls. Positive effects of Rhodiola rhizome on stress resistance and locomotor activity were highest at the ‘middle age’. Conclusions The present data show that long-term food supplementation with R. rosea rhizome not only increases D. melanogaster lifespan, but also delays age-related decline of physical activity and increases stress resistance, what depends on protein-to-carbohydrate ratio of the diet

OXIDIZED LIPIDS DID NOT REDUCE LIFESPAN IN THE FRUIT FLY, Drosophila melanogaster

Aging is often associated with accumulation of oxidative damage in proteins and lipids. However, some studies do not support this view, raising the question of whether high levels of oxidative damage are associated with lifespan. In the current investigation, Drosophila melanogaster flies were kept on diets with 2 or 10% of either glucose or fructose. The lifespan, fecundity, and feeding as well as amounts of protein carbonyls (PC) and lipid peroxides (LOOH), activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), and glutathione reductase activity o

Restriction of glucose and fructose causes mild oxidative stress independently of mitochondrial activity and reactive oxygen species in Drosophila melanogaster

Our recent study showed different effects of glucose and fructose overconsumption on the development of obese phenotypes in Drosophila. Glucose induced glucose toxicity due to the increase in circulating glucose, whereas fructose was more prone to induce obesity promoting accumulation of reserve lipids and carbohydrates (Rovenko et al., Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2015, 180, 75–85). Searching for mechanisms responsible for these phenotypes in this study, we analyzed mitochondrial activity, mitochondrial density, mtROS production, oxidative stress markers and antioxidant defense in fruit flies fed 0.25%, 4% and 10% glucose or fructose. It is shown that there is a complex interaction between dietary monosaccharide concentrations, mitochondrial activity and oxidative modifications to proteins and lipids. Glucose at high concentration (10%) reduced mitochondrial protein density and consequently respiration in flies, while fructose did not affect these parameters. The production of ROS by mitochondria did not reflect activities of mitochondrial complexes. Moreover, there was no clear connection between mtROS production and antioxidant defense or between antioxidant defense and developmental survival, shown in our previous study (Rovenko et al., Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2015, 180, 75–85). Instead, mtROS and antioxidant machinery cooperated to maintain a redox state that determined survival rates, and paradoxically, pro-oxidant conditions facilitated larva survival independently of the type of carbohydrate. It seems that in this complex system glucose controls the amount of oxidative modification regulating mitochondrial activity, while fructose regulates steady-state mRNA levels of antioxidant enzymes

Within-diet variation in rates of macronutrient consumption and reproduction does not accompany changes in lifespan in Drosophila melanogaster

Interventions such as caloric or dietary restriction extend lifespan in organisms spanning from yeast to primates. Despite its positive influence on longevity, dietary restriction has been found to negatively affect reproduction. Many studies have reported negative correlations between lifespan and reproductive characteristics (such as mating rate, fecundity, reproductive period, and others). Such correlation gives the appearance of a resource-based trade-off between these two life-history traits. Here, we have used nutritional geometry to confirm previous findings in flies that dietary macronutrient balance (protein-to-carbohydrate ratio, P:C) impacts both lifespan and reproduction, such that across a series of diets differing in P:C, maximum lifespan was observed at a lower P:C (1:8) than that which supported highest fecundity (1:1.5). We have then addressed the question whether variation among Drosophila melanogasterMeigen (Diptera: Drosophilidae) fruit flies in food intake and egg production within a single dietary treatment is negatively associated with within-diet variation in lifespan, as might be expected under a resource-based trade-off. There was no such associat

High sucrose consumption promotes obesity whereas its low consumption induces oxidative stress in Drosophila melanogaster

The effects of sucrose in varied concentrations (0.25–20%) with constant amount of yeasts in larval diet on development and metabolic parameters of adult fruit fly Drosophila melanogaster were studied. Larvae consumed more food at low sucrose diet, overeating with yeast. On high sucrose diet, larvae ingested more carbohydrates, despite consuming less food and obtaining less protein derived from yeast. High sucrose diet slowed down pupation and increased pupa mortality, enhanced levels of lipids and glycogen, increased dry body mass, decreased water content, i.e. resulted in obese phenotype. Furthermore, it suppressed reactive oxygen species-induced oxidation of lipids and proteins as well as the activity of superoxide dismutase. The activity of catalase was gender-related. In males, at all sucrose concentrations used catalase activity was higher than at its concentration of 0.25%, whereas in females sucrose concentration virtually did not influence the activity. High sucrose diet increased content of protein thiols and the activity of glucose-6-phosphate dehydrogenase. The increase in sucrose concentration also enhanced uric acid level in females, but caused opposite effects in males. Development on high sucrose diets was accompanied by elevated steady-state insulin-like peptide 3 mRNA level. Finally, carbohydrate starvation at yeast overfeeding on low sucrose diets resulted in oxidative stress reflected by higher levels of oxidized lipids and proteins accompanied by increased superoxide dismutase activity. Potential mechanisms involved in regulation of redox processes by carbohydrates are discussed

Parental dietary protein-to-carbohydrate ratio affects offspring lifespan and metabolism in drosophila

Non-genetic inheritance of metabolic state over multiple generations has been widely reported in insects. The present study uses the fruit fly, Drosophila melanogaster, to assess whether lifespan, physiological traits and metabolism are affected by the dietary protein-to-carbohydrate ratio (P:C) of the prior adult generation. Groups of parental flies were fed diets with different P:C ratios. Their progeny groups were raised on the same diet so the only variable in the experiments was the diet fed to the parents. Parental P:C affected the lifespan of female offspring, however had no impact on F1 males survival. Low parental P:C increased feeding rate in progeny. An increase in the P:C ratio from 0.03 to 0.65 decreased the levels of body glucose and trehalose in the offspring and a similar tendency was observed in the levels of circulating hemolymph glucose and trehalose. Offspring also accumulated less triglycerides but more glycogen when parents were fed a low P:C diet. Our study indicates that the parental dietary P:C ration has a strong impact on the lifespan, reproduction, appetite and metabolism in the offspring generation