| 1. BackgroundAging is a problem for the entire human. Due to this, the ecnomics is obviously inhabited. Aging is a process that leads to physiologic decline and an increased vulnerability to disease and death. While the process of aging is complex, advances in aging research have shown that age-related declines in lifespan and healthspan can often be delayed through genetic and environmental manipulation, e.g. diet or pharmacological agents.Epidemiological studies propose that extension of the human lifespan or the reduction of age associated diseases may be achieved by physical exercise and caloric restriction. Calorie restriction (CR) is the most widely used experimental paradigms that extend lifespan in model organisms, which is a condition that calories nutrients are modestly reduced while maintaining adequate nutrition. CR has been reported to extend lifespan and attenuate age-related diseases in a wide variety of organisms including yeast, worms, flies, mice, rats and probably non-human primates, rhesus monkeys.Alrough CR can effectively extend the lifespan, and at the same time reduce dyslipidemia and cholesterol, but it also can produce some obviously side effects, such as influence the body metabolism and make the female animal less eggs and infertility. So people want to find some ways replace CR. Recent studies suggest that dietary composition or the ratio of carbohydrate relative to protein is more important than CR in modulating lifespan.In flies, the ratio of carbohydrate and protein can obviously modulating lifespan. The standard base diet contained 10% sugar and 10% yeast extract in weight/volume; the CR diet had 2.5% sugar and 2.5% yeast extract; the high sugar-low protein diet consisted of 18% sugar and 2% yeast extract; the low sugar-high protein diet contained 2% sugar and 18% yeast extract; and the high-fat diet had 10% sugar,10% yeast extract and 2% palmitic acid. Compare with the standard food, high sugar diet extend the lifespn in both male and female flies, while high protein diet reduce the lifespan. CR diet extend the lifespan between the standard diet and high sugar diet. So the composition of diet play an important role in modulating lifespan.In mice, a study of lifespan in approximately 40 recombinant inbred lines under dietary restriction condition indicates that dietary restriction only extends lifespan in a subset of these mouse lines and even shortens lifespan in some. This suggests that the prolongevity effect of dietary restriction depends on genetic background of the organism.Diets rich in botanicals are known to have numerous health benefits to humans. Clinical trials, animal model and cell-based studies, and biochemical analyses demonstrate that plants contain a wide range of nutrients and biologically active phytochemicals that provide numerous health benefits. Fruits and vegetables are rich in phytochemicals, nutrients and anti-oxidants and their consumption may retard aging. Some of them were called the CR-mimic substances. Acai and resveratrol were regarded as the CR-mimic substances.Acai is a fruit from the palm tree, Euterpe oleracea Mart, indigenous to the Amazon River area in South America. It is commonly used to make beverages, and served as a food additive, and is even used in folk medicine. Acai contains numerous kinds of phytochemicals, particularly, anthocyanins, proanthocyanidins and other flavonoids. Acai possesses unusually high anti-oxidant activity compared to other plant foods based on various anti-oxidant assays, particularly against the superoxide and peroxyl radicals.Resveratrol is identified as a natural compound from grapeskins. It demonstrates that there is an inverse correlation between red wine consumption and the incidence of cardiovascular disease under the fat-rich diets. Resveratrol maybe play an important role in that. After that, there were suceessive reports resveratrol can prevent or slow the progression of some diseases, such as cancer, cardiovascular disease and neurological disorders. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. So here we first investigated whether the resveratrol can extend the Drosophila melanogaster's lifespan or not. Second, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of dietary composition. Finally we want to investigated the underline mechanicism.2. MethodsWe record the life curve of Drosophila melanogaster and calculate the mean lifespan and maximam lifespan. Then we compare the different concentration of acai and resveratrol and then vary the dietary composition influence on Drosophila melanogaster's lifespan. Four types of sugar and yeast extract based diets as control diets were prepared. Then we applied the qRT-PCR to detect the transcription of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. After that, we constructed the SOD1 mutant Drosophila melanogaster useing the RNA interference to find the result of acai and resveratrol on SOD1RNAi Drosophila melanogaster. Finally, we test the food intake between the different treated groups. Food intake was measured using the capillary feeder method (CAFE).3. ResultsAcai can extend the flies lifespan fed on high fat diets. Resveratrol at up to 200μmol/L in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. resveratrol at 400μmol/L extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with down-regulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, acai and resveratrol increased lifespan of superoxide dismutase 1 (sod1) RNAi females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 RNAi males under the culture conditions in this study. We also measured daily food intake of female flies fed with the agar-free high-fat diet supplemented with or without 400μmol/L resveratrol for three consecutive days using the CAFE method. Resveratrol did not change the daily food intake in these flies, indicating that lifespan extension by resveratrol in female flies fed the high-fat diet is not due to the difference in food intake.Six genes were found down-regulated by resveratrol. Among them are Drosophila insulin-like peptide 3 and 5 (dIlp3 and dIlp5) involved in insulin-like signaling. Supplementation of resveratrol also down-regulated glutathione S transferase D1(GstDl) and heat shock protein 68 (Hsp68), two downstream targets of Jun kinase (JNK) signaling pathway, which is a major oxidative stress response pathway and is known to modulate lifespan in several model organisms. In addition, two peroxiredoxin (Prx) genes, Prx2540-1 and Prx6005, were down-regulated by supplementation of resveratrol. Taken together, these findings suggest that supplementation of resveratrol promotes the survival of flies by reducing oxidative damage.Five of the six genes, dIlp3, dIlp5, gstD1, hsp68 and Prx2540-1, down-regulated by resveratrol in flies fed the low sugar-high protein diet, were also down-regulated by resveratrol in flies fed the high fat diet. Supplementation of resveratrol also reduced the transcript level of Prx2540-2 instead of Prx6005. These findings are consistent with what we observed in the case of the low sugar-high protein diet and further support the notion that supplementation of resveratrol can reduce oxidative damage in flies. Acai can upregulated the 1(2)efl genes and downregulated the Pepck genes.4. ConclusionThe prolongevity effect of acai and resveratrol are influenced by dietary composition, only appear on the high fat or high protein diet. And this effect are gender-specific. They can influence the female, not male. The prolongevity effect on sodl RNAi are further support this. Acai and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements. |
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