Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs.

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs. However, the biological functions of PDEVs are not fully understood, and standard isolation protocols are lacking. Here, PDEVs were isolated from four foods with a combination of ultracentrifugation and size exclusion chromatography, and evaluated as vehicles for enhanced transport of synthetic miRNAs. In addition, the role of food-derived EVs as carriers of dietary (poly)phenols and other secondary metabolites was investigated. EVs from broccoli, pomegranate, apple, and orange were efficiently isolated and characterized. In all four sources, 4 miRNA families were present in tissues and EVs. miRNAs present in broccoli and fruit-derived EVs showed a reduced RNase degradation and were ferried inside exposed cells. EVs transfected with a combination of ath-miR159a, ath-miR162a-3p, ath-miR166b-3p, and ath-miR396b-5p showed toxic effects on human cells, as did natural broccoli EVs alone. PDEVs transport trace amounts of phytochemicals, including flavonoids, anthocyanidins, phenolic acids, or glucosinolates. Thus, PDEVs can act as nanocarriers for functional miRNAs that could be used in RNA-based therapy.

Competitive season effects on polyunsaturated fatty acid content in erythrocyte membranes of female football players.

BACKGROUND: An optimal and correctly balanced metabolic status is essential to improve sports performance in athletes. Recent advances in omic tools, such as the lipid profile of the mature erythrocyte membranes (LPMEM), allow to have a comprehensive vision of the nutritional and metabolic status of these individuals to provide personalized recommendations for nutrients, specifically, the essential omega-3 and omega-6 fatty acids, individuating deficiencies/unbalances that can arise from both habitual diet and sportive activity. This work aimed to study the LPMEM in professional female football players during the football season for the first time and compare it with those defined as optimal values for the general population and a control group. METHODS: An observational study was carried out on female football players from the Athletic Club (Bilbao) playing in the first division of the Spanish league. Blood samples were collected at three points: at the beginning, mid-season, and end of the season for three consecutive seasons (2019-2020, 2020-2021, and 2021-2022), providing a total of 160 samples from 40 women. The LPMEM analysis was obtained by GC-FID by published method and correlated to other individual data, such as blood biochemical parameters, body composition, and age. RESULTS: We observed a significant increase in docosahexaenoic acid (DHA) (p 0.048) and total polyunsaturated fatty acid (PUFA) (p 0.021) in the first season. In the second season, we observed a buildup in the membrane arachidonic acid (AA) (p < .001) and PUFA (p < .001) contents when high training accumulated. In comparison with the benchmark of average population values, 69% of the football players showed lower levels of omega-6 dihomo-γ-linolenic acid (DGLA), whereas 88%, 44%, and 81% of the participants showed increased values of AA, eicosapentaenoic acid (EPA), and the ratio of saturated and monounsaturated fatty acids (SFA/MUFA), respectively. Regarding relationships between blood biochemical parameters, body composition, and age with LPMEM, we observed some mild negative correlations, such as AA and SFA/MUFA ratio with vitamin D levels (coefficient = -0.34 p = .0019 and coefficient = -.25 p = .042); DGLA with urea and cortisol (coefficient = -0.27 p < .006 and coefficient = .28 p < .0028) and AA with age (coefficient = -0.33 p < .001). CONCLUSION: In conclusion, relevant variations in several fatty acids of the membrane fatty acid profile of elite female football players were observed during the competitive season and, in comparison with the general population, increased PUFA contents were confirmed, as reported in other sportive activities, together with the new aspect of DGLA diminution, an omega-6 involved in immune and anti-inflammatory responses. Our results highlight membrane lipidomics as a tool to ascertain the molecular profile of elite female football players with a potential application for future personalized nutritional strategies (diet and supplementation) to address unbalances created during the competitive season.

Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review.

Cardiovascular disease (CVD) is a leading cause of death worldwide. Supplementation with the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with lower CVD risk. However, results from randomized controlled trials that examine the effect of omega-3 supplementation on CVD risk are inconsistent. This risk-reducing effect may be mediated by reducing inflammation, oxidative stress and serum triglyceride (TG) levels. However, not all individuals respond by reducing TG levels after omega-3 supplementation. This inter-individual variability in TG response to omega-3 supplementation is not fully understood. Hence, we aim to review the evidence for how interactions between omega-3 fatty acid supplementation and genetic variants, epigenetic and gene expression profiling, gut microbiota and habitual intake of omega-3 fatty acids can explain why the TG response differs between individuals. This may contribute to understanding the current controversies and play a role in defining future personalized guidelines to prevent CVD.

Anti-fatigue and anti-oxidant effects of curcumin supplementation in exhaustive swimming mice via Nrf2/Keap1 signal pathway.

Demands for dietary supplements with anti-fatigue effects are growing fast due to increasing societal demands. Moreover, in highly physically active individuals, there are also significant needs for supplements to improve exercise performance. The present study evaluated the potential anti-fatigue and anti-oxidant effects of curcumin in mice using exhaustive swimming test. Male C57BL/6J mice were randomized into six groups: blank control (Rest), swimming control (Con), Vitamin C (Vc), low-dose curcumin (C50), middle-dose curcumin (C100), and high-dose curcumin (C200). After a 4-week intervention, the mice in all groups except the Rest group were subject to an exhaustive swimming test. Then, mice were sacrificed to examine serum biochemical markers and fatigue-related enzymes. Moreover, the gene and protein expressions of signal transduction factors involved in the Nrf2/Keap1 signaling pathway were measured. The results indicated that curcumin significantly enhanced the exercise tolerance of mice in the exhaustive swimming test. Particularly, the swimming time of mice in the C100 group was increased by 273.5% when compared to that of mice in the Con group. The levels of blood urea nitrogen, blood ammonia, lactic acid, creatine kinase and lactate dehydrogenase in the C100 group were decreased by 13.3%, 21.0%, 18.6%, 16.7% and 21.9%, respectively, when compared to those of mice in the Con group. Curcumin alleviated exercise-induced oxidative stress and significantly enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase by activating the Nrf2 signaling. These findings indicated that curcumin supplementation exerted remarkable anti-oxidant and anti-fatigue effects in mice, providing additional evidence supporting the use of curcumin as functional food, especially by those engaged in sports-related activities.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation.

Evidence suggests there are roles for vitamin K in various chronic disease outcomes, but population-level diet and supplement recommendations are difficult to determine due to high levels of variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, a blood-based epigenome-wide association study (EWAS) comparing responders and non-responders to phylloquinone (vitamin K1) supplementation (NCT00183001) was undertaken in order to better understand the molecular underpinnings of this observed variability. Responders (n = 24) and non-responders (n = 24) were identified in a prior 3-year phylloquinone supplementation trial based on their changes in plasma phylloquinone concentrations. Differential DNA methylation was identified in multiple regions with previously unknown relationships to phylloquinone absorption and metabolism, such as at the TMEM263 locus. A hypothesis-driven analysis of lipid-related genes highlighted a site in the NPC1L1 gene, supplementing existing evidence for its role in phylloquinone absorption. Furthermore, an EWAS for baseline plasma phylloquinone concentrations revealed a strong correlation between the epigenomic signatures of phylloquinone baseline status and response to supplementation. This work can guide future epigenomic research on vitamin K and contributes to the development of more personalized dietary recommendations for vitamin K.

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.

Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the FADS cluster and omega-3 concentrations (top-ranked in the adjusted model: FADS1-rs174547, p = 3.34 × 10-14; FADS1-rs174550, p = 5.35 × 10-14; FADS2-rs1535, p = 5.85 × 10-14; FADS1-rs174546, p = 6.72 × 10-14; FADS2-rs174546, p = 9.75 × 10-14; FADS2- rs174576, p = 1.17 × 10-13; FADS2-rs174577, p = 1.12 × 10-12, among others). We also detected a genome-wide significant association with other genes in chromosome 11: MYRF (myelin regulatory factor)-rs174535, p = 1.49 × 10-12; TMEM258 (transmembrane protein 258)-rs102275, p = 2.43 × 10-12; FEN1 (flap structure-specific endonuclease 1)-rs174538, p = 1.96 × 10-11). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the DNTTIP2 (deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965 p = 1.36 × 10-8. For adherence to MedDiet, we obtained a relevant interaction with the ME1 (malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was ME1-rs3798890 (p = 2.15 × 10-7). In the regional-wide association study, specifically focused on the FADS1/FASD2/FADS3 and ELOVL (fatty acid elongase) 2/ELOVL 5 regions, we detected several statistically significant associations at p < 0.05. In conclusion, our results confirm a robust role of the FADS cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.

Toward the Definition of Personalized Nutrition: A Proposal by The American Nutrition Association.

Personalized nutrition holds tremendous potential to improve human health. Despite exponential growth, the field has yet to be clearly delineated and a consensus definition of the term "personalized nutrition" (PN) has not been developed. Defining and delineating the field will foster standardization and scalability in research, data, training, products, services, and clinical practice; and assist in driving favorable policy. Building on the seminal work of pioneering thought leaders across disciplines, we propose that personalized nutrition be defined as: a field that leverages human individuality to drive nutrition strategies that prevent, manage, and treat disease and optimize health, and be delineated by three synergistic elements: PN science and data, PN professional education and training, and PN guidance and therapeutics. Herein we describe the application of PN in these areas and discuss challenges and solutions that the field faces as it evolves. This and future work will contribute to the continued refinement and growth of the field of PN.Teaching pointsPN approaches can be most effective when there is consensus regarding its definition and applications.PN can be delineated into three main areas of application: PN science and data, PN education and training, PN guidance and therapeutics.PN science and data foster understanding about the impact of genetic, phenotypic, biochemical and nutritional inputs on an individual's health.PN education and training equip a variety of healthcare professionals to apply PN strategies in many healthcare settings.PN professionals have greater ability to tailor interventions via PN guidance and therapeutics.Favorable policy allows PN to be more fully integrated into the healthcare system.

The Contribution of Lipids to the Interindividual Response of Vitamin K Biomarkers to Vitamin K Supplementation.

SCOPE: A better understanding of factors contributing to interindividual variability in biomarkers of vitamin K can enhance the understanding of the equivocal role of vitamin K in cardiovascular disease. Based on the known biology of phylloquinone, the major form of vitamin K, it is hypothesized that plasma lipids contribute to the variable response of biomarkers of vitamin K metabolism to phylloquinone supplementation. METHODS AND RESULTS: The association of plasma lipids and 27 lipid-related genetic variants with the response of biomarkers of vitamin K metabolism is examined in a secondary analysis of data from a 3-year phylloquinone supplementation trial in men (n = 66) and women (n = 85). Year 3 plasma triglycerides (TG), but not total cholesterol, LDL-cholesterol, or HDL-cholesterol, are associated with the plasma phylloquinone response (men: ß = 1.01, p < 0.001, R2  = 0.34; women: ß = 0.61, p = 0.008, R2  = 0.11; sex interaction p = 0.077). Four variants and the TG-weighted genetic risk score are associated with the plasma phylloquinone response in men only. Plasma lipids are not associated with changes in biomarkers of vitamin K function (undercarboxylated osteocalcin and matrix gla protein) in either sex. CONCLUSION: Plasma TG are an important determinant of the interindividual response of plasma phylloquinone to phylloquinone supplementation, but changes in biomarkers of vitamin K carboxylation are not influenced by lipids.

Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.

We recently reported that epicatechin, a bioactive compound that occurs naturally in various common foods, promoted general health and survival of obese diabetic mice. It remains to be determined whether epicatechin extends health span and delays the process of aging. In the present study, epicatechin or its analogue epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to 20-mo-old male C57BL mice fed a standard chow. The goal was to determine the antiaging effect. The results showed that supplementation with epicatechin for 37 wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no significant effect. Consistently, epicatechin improved physical activity, delayed degeneration of skeletal muscle (quadriceps), and shifted the profiles of the serum metabolites and skeletal muscle general mRNA expressions in aging mice toward the profiles observed in young mice. In particular, we found that dietary epicatechin significantly reversed age-altered mRNA and protein expressions of extracellular matrix and peroxisome proliferator-activated receptor pathways in skeletal muscle, and reversed the age-induced declines of the nicotinate and nicotinamide pathway both in serum and skeletal muscle. The present study provides evidence that epicatechin supplementation can exert an antiaging effect, including an increase in survival, an attenuation of the aging-related deterioration of skeletal muscles, and a protection against the aging-related decline in nicotinate and nicotinamide metabolism.-Si, H., Wang, X., Zhang, L., Parnell, L. D., Admed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovás, J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and delays skeletal muscle degeneration in aged mice.

Curcumin supplementation increases survival and lifespan in Drosophila under heat stress conditions.

Harsh climate induces physiological stress thus compromising organismal survival. Our previous studies demonstrated that curcumin (CUR) supplementation increased survival of turtle under heat stress (HS). Here, we span this work to investigate the survival and lifespan of HS Drosophila fed a diet supplemented with CUR. For this purpose, female and male flies were fed basal diet (N) and CUR diet (0.2 mg/g), and exposed to three conditions: 25°C and 29°C continuously, and 34 °C for 2 h at days 1, 4, and 7, then kept at 25 °C. Lifespan analysis showed that, compared to N-25 °C flies, the mean lifespans of N-29 °C and N-34 °C flies were decreased significantly by 8.5-15.7% in males, and 3.7-7.9% in females. Conversely, in the CUR-supplemented diet, mean lifespans of C-29 °C and C-34 °C flies were significantly extended by 8.7-16.4% in males, and by 8.9-12.8% in females, compared to that of temperature-matched flies fed basal diets. The MDA levels of C-34 °C flies were significantly lower than those of N-34 °C flies, indicating CUR reduced oxidative stress caused by HS. Furthermore, CUR palliated the increased oxidative stress caused by HS, by increasing the expression of SOD1, CAT, and PHGPx and decreasing the expression of Hsp70 and Hsp83. Our results indicated that CUR supplementation increases the survival rate of Drosophila by enhancing thermal tolerance. © 2018 BioFactors, 44(6):577-587, 2018.

[The role of omics in precision nutrition: strengths and weaknesses]. / Papel de las ómicas en la nutrición de precisión: fortalezas y debilidades.

Precision medicine has taken huge strides forward in recent years. Although there is still no generally accepted single definition, it basically considers the particular characteristics of each person as relevant in order to better adapt therapeutic or preventive measures in a more personalized fashion. Likewise, the concept of precision nutrition has gathered strength, in which the aim is to provide the best dietary recommendations to prevent or treat a disease in accordance with the characteristics of the individual in question. Of special importance among these characteristics are those based on omics. Initially genomics, and now epigenomics, metabolomics, proteomics and transcriptomics are providing us with new information on the different responses to the diet based on genotype, on new early biomarkers of disease, on dietary intake, or on the regulatory effects of diet. However, precision nutrition can go further still to include much more holistic aspects, not focusing on the disease, but on wellbeing and other indicators of positive health. Hence, other omics have been added to those mentioned above that provide us with a more multidimensional analysis. Gastronomy also plays an important role in precision nutrition. Although we are still at the preliminary validation stage of precision nutrition, this field presents huge potential for development. In this context, we shall review the role of omics in precision nutrition as well as their main strengths and weaknesses.

La medicina de precisión ha tomado un gran impulso en los últimos años. Aunque todavía no existe una definición única generalmente aceptada,se basa en considerar relevantes las características particulares de cada persona para adaptar mejor las medidas terapéuticas o preventivas de una manera más personalizada.De manera análoga, ha surgido el concepto de nutrición de precisión, en el que se pretende proporcionar las mejores recomendaciones dietéticas para prevenir o tratar una enfermedad de acuerdo con las características de la persona. Entre estas características cobran especial relevancia las basadas en las ómicas. Inicialmente, la genómica y, posteriormente, la epigenómica, la metabolómica, la proteómica y la transcriptómica están aportándonos nueva información sobre la distinta respuesta a la dieta basada en el genotipo, sobre nuevos biomarcadores precoces de enfermedad, sobre la ingesta o sobre efectos reguladores de la dieta. Pero la nutrición de precisión todavía puede extenderse mucho más incluyendo aspectos más holísticos que no estén centrados en la enfermedad, sino en el bienestar y otros indicadores de salud positiva. Para ello, a las mencionadas ómicas se han sumado otras ómicas que permiten un análisis más multidimensional.También la gastronomía tiene un papel relevante en la nutrición de precisión. Aunque todavía nos encontramos en una fase preliminar de estudio y de validación en nutrición de precisión, existe un gran potencial en este campo que es necesario desarrollar.En este contexto, revisaremos el papel de las ómicas en la nutrición de precisión, así como sus principales fortalezas y debilidades.

Supplementation with turmeric residue increased survival of the Chinese soft-shelled turtle (Pelodiscus sinensis) under high ambient temperatures.

Turmeric residue (TR), containing residual levels of curcumin, is a solid by-product waste generated after the extraction and separation of curcumin from turmeric root. A feeding trial was conducted to evaluate the effects of TR on the survival of Chinese soft-shelled turtles (SSTs), Pelodiscus sinensis, under a high ambient temperature. A total of 320 female SSTs were assigned randomly to two diets: basal diet (the control group, n=160) and an interventional diet supplemented with 10% TR (the TR group, n=160). Our results demonstrated that supplementation of TR increased the SST survival rate by 135.5%, and superoxide dismutase (SOD) activity of SST liver by 112.8%, and decreased the malondialdehyde (MDA) content of SST liver by 36.4%, compared to the control group. The skin of the SST fed TR showed a golden color. High-performance liquid chromatography (HPLC) analysis indicated that the concentrations of curcumin in TR and the skin of the SST fed TR were (1.69±0.30) and (0.14±0.03) µg/g, respectively. Our observation suggests that supplementation of TR increased the survival rate of SST under high ambient temperatures. We speculated that the increased survival rate and tolerance at the high ambient temperature were associated with the anti-oxidation activity of curcumin from TR. Moreover, curcumin in TR could be deposited in SST skin, which made it more favored in the market of China. Our findings provide new knowledge and evidence to effectively reuse TR as a feed additive in animal and aquatic farming.

Genome-wide expression profiling in muscle and subcutaneous fat of lambs in response to the intake of concentrate supplemented with vitamin E.

BACKGROUND: The objective of this study was to acquire a broader, more comprehensive picture of the transcriptional changes in the L. Thoracis muscle (LT) and subcutaneous fat (SF) of lambs supplemented with vitamin E. Furthermore, we aimed to identify novel genes involved in the metabolism of vitamin E that might also be involved in meat quality. In the first treatment, seven lambs were fed a basal concentrate from weaning to slaughter (CON). In the second treatment, seven lambs received basal concentrate from weaning to 4.71 ± 2.62 days and thereafter concentrate supplemented with 500 mg dl-α-tocopheryl acetate/kg (VE) during the last 33.28 ± 1.07 days before slaughter. RESULTS: The addition of vitamin E to the diet increased the α-tocopherol muscle content and drastically diminished the lipid oxidation of meat. Gene expression profiles for treatments VE and CON were clearly separated from each other in the LT and SF. Vitamin E supplementation had a dramatic effect on subcutaneous fat gene expression, showing general up-regulation of significant genes, compared to CON treatment. In LT, vitamin E supplementation caused down-regulation of genes related to intracellular signaling cascade. Functional analysis of SF showed that vitamin E supplementation caused up-regulation of the lipid biosynthesis process, cholesterol, and sterol and steroid biosynthesis, and it down-regulated genes related to the stress response. CONCLUSIONS: Different gene expression patterns were found between the SF and LT, suggesting tissue specific responses to vitamin E supplementation. Our study enabled us to identify novel genes and metabolic pathways related to vitamin E metabolism that might be implicated in meat quality. Further exploration of these genes and vitamin E could lead to a better understanding of how vitamin E affects the oxidative process that occurs in manufactured meat products.

Supplementation with Major Royal-Jelly Proteins Increases Lifespan, Feeding, and Fecundity in Drosophila.

The major royal-jelly proteins (MRJPs) are the main constituents responsible for the specific physiological role of royal jelly (RJ) in honeybees. Male and female Drosophila flies were fed diets containing either no MRJPs (A) or casein (B) at 1.25% (w/w) of diet or MRJPs at 1.25% (C), 2.50% (D), or 5.00% (E). Diets B, C, D, and E increased mean lifespan by 4.3%, 9.0%, 12.4%, and 13.9% in males and by 5.8%, 9.7%, 20.0%, and 11.8% in females in comparison to results from diet A, respectively. The diet supplemented with 2.50% MRJPs seems to have the optimal dose to improve both physiological and biochemical measures related to aging in both sexes. Interestingly, lifespan extension by MRJPs in Drosophila was positively associated with feeding and fecundity and up-regulation of copper and zinc-superoxide dismutase (CuZn-SOD) and the Egfr-mediated signaling pathway. This study provides strong evidence that MRJPs are important components of RJ for prolonging lifespan in Drosophila.

Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.

BACKGROUND: Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE: We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN: This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS: The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: ß ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (ß ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (ß = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (ß-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS: This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.

Design and development of an instrument to measure overall lifestyle habits for epidemiological research: the Mediterranean Lifestyle (MEDLIFE) index.

OBJECTIVE: To design and develop a questionnaire that can account for an individual's adherence to a Mediterranean lifestyle including the assessment of diet and physical activity patterns, as well as social interaction. DESIGN: The Mediterranean Lifestyle (MEDLIFE) index was created based on the current Spanish Mediterranean food guide pyramid. MEDLIFE is a twenty-eight-item derived index consisting of questions about food consumption (fifteen items), traditional Mediterranean dietary habits (seven items) and physical activity, rest and social interaction habits (six items). Linear regression models and Spearman rank correlation were fitted to assess content validity and internal consistency. SETTING: A subset of participants in the Aragon Workers' Health Study cohort (Zaragoza, Spain) provided the data for development of MEDLIFE. SUBJECTS: Participants (n 988) of the Aragon Workers' Health Study cohort in Spain. RESULTS: Mean MEDLIFE score was 11·3 (sd 2·6; range: 0-28), and the quintile distribution of MEDLIFE score showed a significant association with each of the individual items as well as with specific nutrients and lifestyle indicators (intra-validity). We also quantified MEDLIFE correspondence with previously reported diet quality indices and found significant correlations (ρ range: 0·44-0·53; P<0·001) for the Alternate Healthy Eating Index, the Alternate Mediterranean Diet Index and Mediterranean Diet Adherence Screener. CONCLUSIONS: MEDLIFE is the first index to include an overall assessment of lifestyle habits. It is expected to be a more holistic tool to measure adherence to the Mediterranean lifestyle in epidemiological studies.

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits.

BACKGROUND: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). RESULTS: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033). CONCLUSION: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.