Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis.
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ABSTRACT:
SUBMITTER: Fan SZ
PROVIDER: S-EPMC8672782 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Transgenic engineering of plants is important in both basic and applied research. However, the expression of a transgene can dwindle over time as the plant's small (s)RNA-guided silencing pathways shut it down. The silencing pathways have evolved as antiviral defence mechanisms, and viruses have co-evolved viral silencing-suppressor proteins (VSPs) to block them. Therefore, VSPs have been routinely used alongside desired transgene constructs to enhance their expression in transient assays. However, constitutive, stable expression of a VSP in a plant usually causes pronounced developmental abnormalities, as their actions interfere with endogenous microRNA-regulated processes, and has largely precluded the use of VSPs as an aid to stable transgene expression. In an attempt to avoid the deleterious effects but obtain the enhancing effect, a number of different VSPs were expressed exclusively in the seeds of Arabidopsis thaliana alongside a three-step transgenic pathway for the synthesis of arachidonic acid (AA), an ?-6 long chain polyunsaturated fatty acid. Results from independent transgenic events, maintained for four generations, showed that the VSP-AA-transformed plants were developmentally normal, apart from minor phenotypes at the cotyledon stage, and could produce 40% more AA than plants transformed with the AA transgene cassette alone. Intriguingly, a geminivirus VSP, V2, was constitutively expressed without causing developmental defects, as it acts on the siRNA amplification step that is not part of the miRNA pathway, and gave strong transgene enhancement. These results demonstrate that VSP expression can be used to protect and enhance stable transgene performance and has significant biotechnological application.
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Project description:The purpose of this study is to determine whether dietary nitrate supplementation improves performance in cardiopulmonary exercise testing (CPET).
| 2180461 | ecrin-mdr-crc
Project description:There is increasing interest in the use of a ketogenic diet for various adult disorders; however, the ability of adults to generate ketones is unknown. Our goal was to challenge the hypothesis that there would be no difference between adults and children regarding their ability to enter ketosis.MethodsTwo populations were studied, both treated with identical very low-carbohydrate high-fat diets: a retrospective series of children with epilepsy or/and metabolic disorders (2009-2016) and a prospective clinical trial of adults with glioblastoma. Dietary intake was assessed based upon written food diaries and 24-h dietary recall. Ketogenic ratio was calculated according to [grams of fat consumed]/[grams of carbohydrate and protein consumed]. Ketone levels (β-hydroxybutyrate) were measured in blood and/or urine.ResultsA total of 168 encounters amongst 28 individuals were analyzed. Amongst both children and adults, ketone levels correlated with nutritional ketogenic ratio; however, the absolute ketone levels in adults were approximately one quarter of those seen in children. This difference was highly significant in a multivariate linear regression model, p < 0.0001.ConclusionsFor diets with comparable ketogenic ratios, adults have lower blood ketone levels than children; consequently, high levels of nutritional ketosis are unobtainable in adults.
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Project description:A double-blinded, placebo-controlled, cross-over design was used to investigate whether two different sodium citrate dihydrate (Na-CIT) supplementation protocols improve 200 m swimming performance in adolescent swimmers.Ten, male swimmers (14.9?±?0.4 years of age; 63.5?±?4 kg) performed four 200 m time trials with the following treatments: acute (ACU) supplementation (0.5 g kg(-1) administered 120 min pre-trial), acute placebo (PLC-A), chronic (CHR) supplementation (0.1 g?kg(-1) for three days and 0.3 g kg(-1) on the forth day 120 min pre-trial), and chronic placebo (PLC-C). The order of the trials was randomized, with at least a six-day wash-out period between trials. Blood samples were collected by finger prick pre-ingestion, 100 min post-ingestion, and 3 min post-trial. Performance time, rate of perceived exertion, pH, base excess, bicarbonate and lactate concentration were measured.Post-ingestion bicarbonate and base excess were higher (P?<?0.05) in both the ACU and CHR trials compared to placebo showing adequate pre-exercise alkalosis. However, performance time, rate of perceived exertion as well as post-trial pH and lactate concentration were not significantly different between trials. Further analysis revealed that five swimmers, identified as responders, improved their performance time by 1.03% (P?<?0.05) and attained higher post-trial lactate concentrations in the ACU versus PLC-A trial (P?<?0.05). They also had significantly higher post-trial lactate concentrations compared to the non-responders in the ACU and CHR trials.Acute supplementation of Na-CIT prior to 200 m swimming performance led to a modest time improvement and higher blood lactate concentrations in only half of the swimmers while the chronic Na-CIT supplementation did not provide any ergogenic effect in this group of adolescent swimmers.Clinicaltrials.gov NCT01835912.
| S-EPMC4061773 | biostudies-literature
Project description:This study investigated the effects of dietary Arginine (Arg) on performance, intestinal antioxidative capacity, immunity, and gut microbiota in Chinese yellow-feathered chickens. One thousand two hundred 1-day-old female Qingyuan partridge chickens were randomly assigned to 5 groups with 6 replicates of 40 birds each. Chickens were fed diets with 5 levels of total Arg (8.5, 9.7, 10.9, 12.1, and 13.3 g/kg) without antibiotics for 30 d. The ADFI, ADG, and feed conversion ratio were improved with dietary Arg levels (P < 0.05). The proportions of CD3+ and CD4+/CD8+ lymphocytes responded in a linear (P < 0.05) manner and those of CD4+ in a linear or quadratic (P < 0.05) manner as dietary Arg levels increased. Dietary Arg level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the gene expression of glutathione peroxidase 1, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, and the activities of glutathione peroxidase and total antioxidative capacity in the jejunum and ileum. The relative expression of IL-1?, myeloid differentiation primary response 88, and Toll-like receptor 4 decreased linearly (P < 0.05) in the ileum with increasing dietary Arg levels; secretory IgA contents were increased. In addition, sequencing data of 16S rRNA indicated that dietary Arg increased the relative abundance of Firmicutes phylum, Romboutsia and Candidatus Arthromitus genera, while decreased that of Clostridium sensu stricto 1. A diet containing 12.1 g Arg/kg promoted growth performance, intestinal antioxidation, and innate immunity and modulated gut microbiota in yellow-feathered chickens.
| S-EPMC7705054 | biostudies-literature
Project description:RationaleDietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxide. Such effects include improvement in cardiovascular, renal and metabolic function, which is partly mediated via reduction of oxidative stress. A recent study even indicates that low dose of dietary nitrite extends life span in fruit flies.MethodsIn this study, 200 middle-aged Wistar rats of both sexes were supplemented with nitrate or placebo in the drinking water throughout their remaining life and we studied longevity, biochemical markers of disease, vascular reactivity along with careful determination of the cause of death.ResultsDietary nitrate did not affect life span or the age-dependent changes in markers of oxidative stress, kidney and liver function, or lipid profile. Ex vivo examination of vascular function, however, showed improvements in endothelial function in rats treated with nitrate. Neoplasms were not more common in the nitrate group.ConclusionWe conclude that chronic treatment with dietary nitrate does not affect life span in rats nor does it increase the incidence of cancer. In contrast, vascular function was improved by nitrate, possibly suggesting an increase in health span.
| S-EPMC8683768 | biostudies-literature
Project description:alpha-Tocopherol (alpha-Toc) enhances T cell function, whereas little is known in this regard for tocotrienols (T3), the less-known members of the vitamin E family. We pair-fed young (4 mo) and old (23 mo) C57BL/6 mice 0.1% Tocomin 50%, a mixture of T3 and alpha-Toc or a control diet containing an equal amount of alpha-Toc for 6 wk. As expected, lymphocyte proliferation was lower in the old mice compared with the young mice. Lymphocyte proliferation in the old T3 group was significantly higher than that in the old control group, whereas no significant difference was found in young mice. Splenocytes from old mice produced less interleukin (IL)-2, IL-4, IL-6, and IL-10 compared with young mice, whereas no significant age-related difference was found in IL-1beta, tumor necrosis factor-alpha, and interferon-gamma. T3 feeding was associated with a higher IL-1beta production in old mice but not in young mice. Peritoneal macrophages from old mice produced significantly more IL-1beta, IL-6, IL-10, and prostaglandin E(2) (PGE(2)) compared with those from young mice. Mice of both ages fed T3 had higher production of IL-1beta but not PGE(2) or other cytokines. In the in vitro study, splenocytes isolated from young and old mice were supplemented with the purified form of each individual T3 (0.01-10 mumol/L) and mitogen-stimulated cell proliferation was determined. All T3 enhanced lymphocyte proliferation in old but not young mice with a potency order of alpha- > gamma- > delta-T3. Together, these results suggest a beneficial effect of T3 in improving the age-related decline in T cell function.
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Project description:Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice. Treatment with hypolipidemic agents to lower circulating acetoacetate levels or an inhibitory homolog of acetoacetate, dehydroacetic acid, to antagonize acetoacetate-BRAF V600E binding attenuated BRAF V600E tumor growth. These findings reveal a signaling basis underlying a pathogenic role of dietary fat in BRAF V600E-expressing melanoma, providing insights into the design of conceptualized "precision diets" that may prevent or delay tumor progression based on an individual's specific oncogenic mutation profile.
| S-EPMC5299059 | biostudies-literature
Project description:Dietary restriction increases lifespan and slows the onset of age-associated disease in organisms from yeast to mammals. In humans, several age-related diseases are associated with aberrant protein folding or aggregation, including neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. We report here that dietary restriction dramatically suppresses age-associated paralysis in three nematode models of proteotoxicity. Similar to its longevity-enhancing properties, dietary restriction protects against proteotoxicity by a mechanism distinct from reduced insulin/IGF-1-like signaling. Instead, the heat shock transcription factor, hsf-1, is required for enhanced thermotolerance, suppression of proteotoxicity, and lifespan extension by dietary restriction. These findings demonstrate that dietary restriction confers a general protective effect against proteotoxicity and promotes longevity by a mechanism involving hsf-1.
| S-EPMC2709959 | biostudies-other
Project description:Background:Bio-based production of organic acids promises to be an attractive alternative for the chemicals industry to substitute petrochemicals as building-block chemicals. In recent years, itaconic acid (IA, methylenesuccinic acid) has been established as a sustainable building-block chemical for the manufacture of various products such as synthetic resins, coatings, and biofuels. The natural IA producer Aspergillus terreus is currently used for industrial IA production; however, the filamentous fungus Aspergillus niger has been suggested to be a more suitable host for this purpose. In our previous report, we communicated the overexpression of a putative cytosolic citrate synthase citB in an A. niger strain carrying the full IA biosynthesis gene cluster from A. terreus, which resulted in the highest final titer reported for A. niger (26.2 g/L IA). In this research, we have attempted to improve this pathway by increasing the cytosolic acetyl-CoA pool. Additionally, we have also performed fermentation optimization by varying the nitrogen source and concentration. Results:To increase the cytosolic acetyl-CoA pool, we have overexpressed genes acl1 and acl2 that together encode for ATP-citrate lyase (ACL). Metabolic engineering of ACL resulted in improved IA production through an apparent increase in glycolytic flux. Strains that overexpress acl12 show an increased yield, titer and productivity in comparison with parental strain CitB#99. Furthermore, IA fermentation conditions were improved by nitrogen supplementation, which resulted in alkalization of the medium and thereby reducing IA-induced weak-acid stress. In turn, the alkalizing effect of nitrogen supplementation enabled an elongated idiophase and allowed final titers up to 42.7 g/L to be reached at a productivity of 0.18 g/L/h and yield of 0.26 g/g in 10-L bioreactors. Conclusion:Ultimately, this study shows that metabolic engineering of ACL in our rewired IA biosynthesis pathway leads to improved IA production in A. niger due to an increase in glycolytic flux. Furthermore, IA fermentation conditions were improved by nitrogen supplementation that alleviates IA induced weak-acid stress and extends the idiophase.
| S-EPMC6767652 | biostudies-literature