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Extension of Drosophila Lifespan by Rhodiola rosea Depends on Dietary Carbohydrate and Caloric Content in a Simplified Diet

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Abstract

The root and rhizome extract of Rhodiola rosea has been extensively used in traditional medicine to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. We also previously found that the extract can act independently of dietary restriction (DR), a treatment that can extend lifespan in a range of model organisms. In flies, DR is implemented through a reduction in dietary yeast content. Here, we report that the ability of R. rosea extract to extend lifespan in flies is dependent on the carbohydrate and caloric content when supplemented with a simplified diet composed of yeast and sucrose. R. rosea extract elevated the sugar content in flies and down-regulated hexokinase expression, suggesting that it perturbs carbohydrate metabolism in flies. In our previous studies, bananas, barley malt, and corn syrup provided dietary carbohydrates, and R. rosea extract could extend lifespan with a range of caloric levels. We conclude that the lifespan-extending effect of R. rosea extract in flies is dependent on dietary carbohydrate and caloric contents coupled with an interaction with complex dietary components present in bananas, barley, or corn.

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... However, for these animals a slightly reduced body weight was determined. In contrast to that and in line with a previous report (Schriner et al., 2016), 2.5% roseroot extract did not alter the triglyceride level and body weight of female flies. ...
... In the second model, D. melanogaster, supplementation of 2.5% avens root extract but not of 2.5% roseroot extract resulted in the reduction of the triacylglyceride level in female fruit flies that were fed a starch-rich diet. In good accordance with this, Schriner et al. (2016) reported that when supplementing the Drosophila diet with the same concentration of roseroot extract, the fat and protein levels of fruit flies were not affected independent on the carbohydrate content of the diet (0.09% FIGURE 6 | The impact of root extracts on body weight and lipid storage in D. melanogaster. Female D. melanogaster were raised on a 10% starch, 4% yeast extract diet supplemented with 1.8 μg/ml acarbose, 2.5% avens root and 2.5% roseroot extract, respectively. ...
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Medicinal plant extracts are becoming increasingly important as an alternative for traditional drugs against diabetes mellitus (DM). For this reason, we initialized a target-based screening of 111 root extracts from an open access plant extract library (PECKISH) by ascertaining their in-vitro inhibitory efficacy on α-glucosidase. The two most active extracts Geum urbanum L. (roseroot) and Rhodiola rosea L. (avens root) were further tested for their antidiabetic activities in terms of their impact on different regulatory key points of glucose homeostasis. To this end, various enzyme-and cell culture-based in-vitro assays were employed including the determination of sodium-dependent glucose transporter 1 (SGLT1) activity in Caco-2 monolayers by Ussing chambers and of glucose transporter 4 (GLUT4) translocation in a GFP-reporter cell line. Subsequently, the antidiabetic potential of the root extracts were further evaluated in in-vivo models, namely hen's eggs test and the fruit fly Drosophila melanogaster. Avens root extract was found to be a more potent inhibitor of the enzymes α-glucosidase and dipeptidyl peptidase-4 (DPP4) than roseroot extract. Most importantly, only avens root extract exhibited antidiabetic activity in the two in-vivo models eliciting a reduced blood glucose level in the in-ovo model and a decline of the triglyceride level in a dietary starch-induced D. melanogaster obesity model. Analyses of the polyphenolic composition of the avens root extract by HPLC revealed a high content of ellagic acid and its derivatives as well as ellagitannins such as pedunculagin, stenophyllanin, stachyurin, casuarinin and gemin A. In conclusion, avens root extract represents a promising medicinal plant that should be considered in further in-vivo studies on hyperglycemia in laboratory rodents and humans.
... The fruit fly (Drosophila melanogaster) has emerged as a powerful model for investigating the effects of diet on both physiological and disease-like states. Studies in flies have revealed that diet has substantial effects on lifespan [1][2][3][4][5] , egg-laying 6 , metabolism 7 , fat deposition 8 , perceived nutritional value of food 9 , food choice 10 , sleep 11 and a host of other phenotypes 4,5,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] . Flies are housed on solid, agar-based media for days at a time in most laboratory studies. ...
... The fruit fly (Drosophila melanogaster) has emerged as a powerful model for investigating the effects of diet on both physiological and disease-like states. Studies in flies have revealed that diet has substantial effects on lifespan [1][2][3][4][5] , egg-laying 6 , metabolism 7 , fat deposition 8 , perceived nutritional value of food 9 , food choice 10 , sleep 11 and a host of other phenotypes 4,5,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] . Flies are housed on solid, agar-based media for days at a time in most laboratory studies. ...
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... Rhodiola rosea extracts can extend lifespan at different caloric levels. The effect of R. rosea extracts on lifespan was independent of caloric restriction-related signaling pathways, including SIR2 proteins, insulin, and insulin-like growth factor signaling, and the TOR in fruit flies [77,82], but dependent on diet composition (in particular protein-to-carbohydrate ratios or sucrose contents) and expression of Msn2/Msn4 and Yap1 regulatory proteins [80]. The lifespan extension of Rhodiola rosea extracts was not seen in diets with high protein-to-carbohydrate ratios [77,82]. ...
... The effect of R. rosea extracts on lifespan was independent of caloric restriction-related signaling pathways, including SIR2 proteins, insulin, and insulin-like growth factor signaling, and the TOR in fruit flies [77,82], but dependent on diet composition (in particular protein-to-carbohydrate ratios or sucrose contents) and expression of Msn2/Msn4 and Yap1 regulatory proteins [80]. The lifespan extension of Rhodiola rosea extracts was not seen in diets with high protein-to-carbohydrate ratios [77,82]. In addition, the physiological state of an organism affected the beneficial effect of Rhodiola rosea extracts on longevity [81]. ...
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... 37 However, it may depend on carbohydrate or caloric content of the background diet. 40 Contrary to findings in Jafari et al., 17 R. rosea significantly reduced early fecundity (-29%) and average fecundity (-18%). Late fecundity was not affected. ...
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Healthspan science aims to add healthy, functional years to human life. Many different methods of improving healthspan have been investigated, chiefly focusing on just one aspect of an organism's health such as survival. Studies in Drosophila melanogaster have demonstrated that a reversal to a long-abandoned ancestral diet results in improved functional health, particularly at later ages. Meanwhile, pharmaceutical studies have demonstrated that botanical extracts have potent anti-aging properties, capable of extending the mean lifespan of D. melanogaster by up to 25%, without a decrease in early fecundity. Here we combine these two different approaches to healthspan extension to examine whether a combination of such treatments results in a synergistic or antagonistic effect on Drosophila healthspan. One botanical extract, derived from Rhodiola rosea, mimicked the effects of the ancestral apple diet with better performance at later ages compared to the control. Another extract, derived from Rosa damascena, decreased age-specific survivorship when combined with the apple diet providing support for the "Poisoned Chalice" hypothesis that combinations of various supplements or diets can elicit adverse physiological responses. More experiments in model organisms should be completed researching the effects of combining healthspan-extending substances in various diet backgrounds.
... Fleming et al. [78] pointed out that Drosophila was a choice animal model to investigate longevity-promoting activities of a variety substances, like nutraceuticals, as flies seem to show many of the cellular senescence characteristics observed in mammals. Schriner et al. [79] showed that barley malts had the ability to increase the lifespan of Drosophila individuals, our results being in agreement for the lowest and highest concentrations tested showing an expansion of life of 7 and 8 days respectively. Unfortunately, no previous studies about lifespan have been found for the rest of the studied samples. ...
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Background: Czech beers are unique because they are brewed using specific technology at a particular latitude and for being entirely produced in the area of the Czech Republic. The purpose of this work is the evaluation of toxicological effects of a variety of freeze-dried Czech beers, their raw materials (malts, hops and yeast) and processed-beer (wort, hopped wort and young beer). Methods: In vivo assays to evaluate the safety and protective effects in the Drosophila melanogaster eukaryotic system, and the in vitro evaluations of chemopreventive and DNA damage activity using the HL-60 tumour human cell line were carried out. Results: The safe effects for all the analysed substances and general protective effects against H2O2 were shown both at the individual and genomic level in the Drosophila animal model, with some exceptions. Moreover, all the substances were able to inhibit the tumour cell growth and to induce DNA damage in the HL-60 cells at different levels (proapoptotic, single/double strands breaks and methylation status). Conclusions: The promising effects shown by freeze-dried Czech beers due to their safety, protection against a toxin, chemopreventive potential and the induction of DNA damage in tumour cells, allow the proposition of Czech beer as a beverage with nutraceutic potential.
... Fruit flies are an important genetic model organism for investigating the molecular basis of a plethora of physiological outputs including alcoholrelated behaviors, 11,14-31 food consumption, 66,81 and responses to diet. 67,85,[89][90][91][92][93][94][95][96][97] To the best of our knowledge, our studies are the first to integrate these three areas of biology in the fly. We find that increasing the concentration of yeast in the diet, but not increasing other dietary components or decreasing all components of our standard medium, makes flies resistant to ethanol sedation. ...
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Abuse of alcohol is a major clinical problem with far‐reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol‐related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast‐induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet‐induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol‐related behavior in other species. Flies fed a high yeast diet consume more nutrients, have decreased levels of internal ethanol when exposed to ethanol vapor and require longer exposure to ethanol to become sedated (ie, increased ST50). Our studies implicate serotonergic neurons as key regulators of nutrient consumption and therefore, the effect of dietary yeast on ethanol sedation in flies.
... The second nutraceutical component in SC100+ is Rhodiola rosea root extract, which helps to reduce several types of stress in humans [20,21]. Rhodiola rosea extracts also have extended lifespan in several animal models [22][23][24][25], which suggest a positive effect on life expectancy. ...
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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.
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