Chili-supplemented food decreases glutathione-S-transferase activity in Drosophila melanogaster females without a change in other parameters of antioxidant system.

OBJECTIVES: Many plant-derived anti-aging preparations influence antioxidant defense system. Consumption of food supplemented with chili pepper powder was found to extend lifespan in the fruit fly, Drosophila melanogaster. The present study aimed to test a connection between life-extending effect of chili powder and antioxidant defense system of D. melanogaster. METHODS: Flies were reared for 15 days in the mortality cages on food with 0% (control), 0.04%, 0.12%, 0.4%, or 3% chili powder. Antioxidant and related enzymes, as well as oxidative stress indices were measured. RESULTS: Female flies that consumed chili-supplemented food had a 40-60% lower glutathione-S-transferase (GST) activity as compared with the control cohort. Activity of superoxide dismutase (SOD) was about 37% higher in males that consumed food with 3% chili powder in comparison with the control cohort. Many of the parameters studied were sex-dependent. CONCLUSIONS: Consumption of chili-supplemented food extends lifespan in fruit fly cohorts in a concentration- and gender-dependent manner. However, this extension is not mediated by a strengthening of antioxidant defenses. Consumption of chili-supplemented food does not change the specific relationship between antioxidant and related enzymes in D. melanogaster, and does not change the linkage of the activities of these enzymes to fly gender.

Chili pepper extends lifespan in a concentration-dependent manner and confers cold resistance on Drosophila melanogaster cohorts by influencing specific metabolic pathways.

Chili powder is a widely used spice with pungent taste, often consumed on a daily basis in several countries. Recent prospective cohort studies showed that the regular use of chili pepper improves healthspan in humans. Indeed, chili pepper fruits contain phenolic substances which are structurally similar to those that show anti-aging properties. The objective of our study was to test whether consumption of chili-supplemented food by the fruit fly, Drosophila melanogaster, would prolong lifespan and in which way this chili-supplemented food affects animal metabolism. Chili powder added to food in concentrations of 0.04%-0.12% significantly extended median lifespan in fruit fly cohorts of both genders by 9% to 13%. However, food supplemented with 3% chili powder shortened lifespan of male cohorts by 9%. Lifespan extension was accompanied by a decrease in age-independent mortality (i.e., death in early ages). The metabolic changes caused by consumption of chili-supplemented food had a pronounced dependence on gender. A characteristic of both fruit fly sexes that ate chili-supplemented food was an increased resistance to cold shock. Flies of both sexes had lower levels of hemolymph glucose when they ate food supplemented with low concentrations of chili powder, as compared with controls. However, males fed on food with 3% chili had lower levels of storage lipids and pyruvate reducing activity of lactate dehydrogenase compared with controls. Females fed on this food showed lower activities of hexokinase and pyruvate kinase, as well as lower ADP/O ratios, compared with control flies.

Herbicide Roundup shows toxic effects in nontarget organism Drosophila.

Glyphosate-based herbicide Roundup, as the most employed herbicide used for multiple purposes in agriculture, adversely affects nontarget organisms. We tested the effects of Roundup applied at larval and adult stages. Roundup caused developmental delay and increased larvae mortality. Roundup treatment reduced hemolymph glucose and glycogen levels in adult flies of both sexes at the highest concentration tested. Sex-dependent diverse effects were found in catalase and Cu,Zn superoxide dismutase (Cu,Zn-SOD) activities. Decreased aconitase activity, contents of thiols, and lipid peroxides were found after larval Roundup exposure. Furthermore, chronic exposure to adult flies decreased appetite, body weight, and shortened lifespan. Thus, our results suggest that high concentrations of Roundup are deleterious to both larvae and adults, resulting in a shift of the metabolism and antioxidant defense system in Drosophila melanogaster.

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.

TOR signaling inhibition in intestinal stem and progenitor cells affects physiology and metabolism in Drosophila.

In all eukaryotic organisms, the control of growth, metabolism, reproduction, and lifespan is realized by interactions of genetic and environmental signals. An important player in the regulatory network is the target of rapamycin (TOR) signaling pathway, which is triggered by nutritional cues. Given the pivotal role of TOR in regulating multiple processes in organisms, we inhibited TOR by inducible expression of specific RNAi in Drosophila intestinal stem and progenitor cells or progenitor cells alone. We found that TOR inhibition in stem and progenitor cells shortened the lifespan on both regular diet and under malnutrition. Moreover, flies became more short-lived under starvation or oxidative stress conditions if TOR was inhibited. TOR-RNAi expression resulted in a decrease in body glycogen and TAG levels. All these physiological and metabolic changes might be partially explained by significant changes in mRNA levels for genes encoding the Drosophila insulin-like peptides (dilp2, dilp3 and dilp5) with subsequent effects on insulin signaling to modulate gene expression in peripheral tissues (e.g. tobi and pepck transcripts). In the gut, a strong increase in transcript levels of cytokines upd2, upd3 and downstream target socs36e of the JAK/STAT signaling pathway in the gut indicate an important role for this signaling pathway when TOR is inhibited.

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

The article Alternative NADH dehydrogenase extends lifespan and increases resistance to xenobiotics in Drosophila, written by Dmytro V. Gospodaryov. Olha M. Strilbytska. Uliana V. Semaniuk. Natalia V. Perkhulyn. Bohdana M. Rovenko. Ihor S. Yurkevych. Ana G. Barata. Tobias P. Dick. Oleh V. Lushchak and Howard T. Jacobs, was originally published electronically on the publisher's internet portal on 20 November 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 27 January 2020 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The original article has been corrected.

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.

Anise Hyssop Agastache foeniculum Increases Lifespan, Stress Resistance, and Metabolism by Affecting Free Radical Processes in Drosophila.

Anise hyssop, Agastache foeniculum, is a widely used medicinal herb with known antioxidant properties. We studied how dietary supplementation with dried A. foeniculum leaf powder affected physiological and metabolic traits as well as activities of antioxidant enzymes and markers of oxidative stress in Drosophila melanogaster. Dietary hyssop extended the lifespan in a sex and genotype independent manner over a broad range of concentrations up to 30 mg/ml. Dietary supplementation with the herb significantly increased fecundity, resistance to oxidative stress and starvation. Higher transcript levels of Drosophila insulin-like peptide (dilp2) and decreased dilp3 and dilp6 transcripts together with increased levels of glycogen and triacylglycerols support an alteration of insulin signaling by the plant extract. Increased enzymatic activities of superoxide dismutase and aconitase as well as elevated protein and low molecular mass thiols also supported an alteration of free radical process in flies treated with dietary A. foeniculum leaf powder. Thus, physiological and metabolic traits as well as free radical processed may be affected by active compounds detected in extracts of anise hyssop leaves and contribute to the increased lifespan and reproductive (egg-laying) activity observed.

Implications of amino acid sensing and dietary protein to the aging process.

Every organism must adapt and respond appropriately to the source of nutrients available in its environment. Different mechanisms and pathways are involved in detecting the intracellular and extracellular levels of macronutrients including amino acids. Detection of amino acids in food sources is provided by taste cells expressing T1R1 and T1R3 type receptors. Additionally, cells of the intestine, pancreas or heart sense amino acids extracellularly. Neuronal and hormonal regulation integrates and coordinates the signals at the organismal level. Amino acid-sensitive mechanisms including GCN2 protein, mTOR and LYNUS machinery adjust cellular process according to the availability of specific amino acids. Triggering these mechanisms by genetic manipulations or by external manipulations with diets has a significant impact on lifespan. In model organisms, the restriction of protein or specific amino acids within the diet leads to lifespan-extending effects. However, the translation of results from model organisms to application in humans has to take into account lifestyle, psychology, social aspects and the possibility to choose what to eat and how it is cooked.

Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila.

The TOR (target of rapamycin) signaling pathway and the transcriptional factor Myc play important roles in growth control. Myc acts, in part, as a downstream target of TOR to regulate the activity and functioning of stem cells. Here we explore the role of TOR-Myc axis in stem and progenitor cells in the regulation of lifespan, stress resistance and metabolism in Drosophila. We found that both overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased the lifespan and starvation resistance of flies. TOR activation caused higher survival under malnutrition conditions. Furthermore, we demonstrate gut-specific activation of JAK/STAT and insulin signaling pathways to control gut integrity. Both genetic manipulations had an impact on carbohydrate metabolism and transcriptional levels of metabolic genes. Our findings indicate that activation of the TOR-Myc axis in midgut stem and progenitor cells influences a variety of traits in Drosophila.