Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention.
Ontology highlight
ABSTRACT:
SUBMITTER: Riscuta G
PROVIDER: S-EPMC5037878 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention.
The Journal of nutrition 20160824 10
The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age-related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age-related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in ...[more]
Similar Datasets
Project description:Although there is growing epidemiological, preclinical and clinical evidence suggesting that low vitamin D intake, exposure and/or status is associated with an increased risk of various types of cancer, the optimum amount needed remains controversial. Furthermore, there is evidence that a U- or J-shaped response curve exist between 25(OH)D and certain cancers. Increasing information about the impact of genetic variation, especially polymorphisms that influence absorption, transport, metabolism and associated molecular targets, should help clarify inconsistencies in the data regarding vitamin D's effect on cancer risk. Rather than focusing on the main effects of a few variants of these genes alone, future studies need to consider gene-nutrient or environmental interactions. Nutrigenomics should clarify who might benefit and be placed at risk because of vitamin D exposure.
| S-EPMC3219444 | biostudies-literature
Project description:BackgroundAlthough nutrition interventions are a widely accepted resource for the prevention of long-term health conditions, current approaches have not adequately reduced chronic disease morbidity. Nutrigenomics has great potential; however, it is complicated to implement. There is a need for products based on nutrition-related gene test results that are easily understood, accessible, and used.ObjectiveThe primary objective of this study was to compare a nonpractitioner-assisted direct-to-consumer self-driven approach to nutrigenomics versus an integrated and personalized practitioner-led method.MethodsThis 4-month study used a mixed-methods design that included (1) a phase 1 randomized controlled trial that examined the effectiveness of a multifaceted, nutrition-based gene test (components assessed included major nutrients, food tolerances, food taste and preferences, and micronutrients) in changing health behaviors, followed by (2) a qualitative investigation that explored participants' experiences. The study recruited 55 healthy males and females (aged 35-55 years) randomized as a 2:1 ratio where 36 received the intervention (gene test results plus integrated and personalized nutrition report) and 19 were assigned to the control group (gene test results report emailed). The primary outcomes of interest measures included changes in diet (nutrients, healthy eating index), changes in measures on General Self-efficacy and Health-Related Quality of Life scales, and anthropometrics (body mass index, waist-to-hip ratio) measured at baseline, post intervention (3 and 6 weeks), and the final visit (week 9 post intervention).ResultsOf the 478 individuals who expressed interest, 180 were invited (37.7%, 180/478) and completed the eligibility screening questionnaire; 73 of the 180 invited individuals (40.5%) were deemed eligible. Of the 73 individuals who were deemed to be eligible, 58 completed the baseline health questionnaire and food records (79%). Of these 58 individuals, 3 were excluded either because they did not complete all required data collection forms or were later found to be ineligible. The final sample (n=55) was mostly female (75%), married (85%), and those who had completed postsecondary education (62%).ConclusionsThis study will leverage quantitative and qualitative findings, which will guide the development of nutrigenomics-based products in electronic formats that are user-friendly for consumers and health professionals. Although the quantitative data have not been analyzed yet, the overwhelming interest in the study and the extremely high retention rate show that there is a great degree of interest in this field. Given this interest and the fact that nutrigenomics is an evolving science, a need for continued research exists to further the understanding of the role of genetic variation and its role and applications in nutrition practice.Trial registrationClinicaltrials.gov NCT03310814; http://clinicaltrials.gov/ct2/show/NCT03310814 (Archived by WebCite at http://www.webcitation.org/6yGnU5deB).Registered report identifierRR1-10.2196/9846.
| S-EPMC6018240 | biostudies-literature
Project description:Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids [PUFA] such as eicosapentanoic acid [EPA] and docosahexanoic acid [DHA] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA.
The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity.
The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity
| 2130139 | ecrin-mdr-crc
Project description:Nutrigenomics is an emerging science which investigates a certain area of nutrition that uses molecular tools to search access and understand the several responses obtained through a certain diet applied between individual and population groups. The increased need for the use of personalised nutrition in patients is increasing and research is being made on its possible effects. However, research on nutrigenomics and in particular, obesity is still ongoing. Following a current metanalysis on thirty-eight nutrigenomics genes, it seems that a definite association between the genes usually examined in nutrigenomics testing and several diet-related diseases is lacking, even though there is a limited number of studies associating them. In 2014, literature search results in a great number of studies on several polymorphisms. This heterogeneity could only show the way towards new research aims. Nutrigenomics was born due to the need to move from Epidemiology and Physiology to Molecular Biology and Genetics. Currently, there are steps that need to be considered in order for nutrigenomics to be applied: the genes, the gene/protein network, and the strategy towards the determination of the nutrients' influence on gene/protein expression. It is certainly an interesting evolving science with many areas to be investigated further and from different perspectives, as it involves ethics, medicine, genetics and nutrition.
| S-EPMC4745366 | biostudies-literature
Project description:Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin's effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin's longevity effects from effects on aging itself.
| S-EPMC3726163 | biostudies-other
Project description:Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
| S-EPMC5940111 | biostudies-literature
Project description:To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%-11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole (HBX), and INT-767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose-control drugs in humans.
| S-EPMC6413665 | biostudies-literature
Project description:The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018).
| S-EPMC6649668 | biostudies-literature
Project description:In invertebrates, reproductive output and lifespan are profoundly impacted by dietary macronutrient balance, with these traits achieving their maxima on different diet compositions, giving the appearance of a resource-based tradeoff between reproduction and longevity. For the first time in a mammal, to our knowledge, we evaluate the effects of dietary protein (P), carbohydrate (C), fat (F), and energy (E) on lifespan and reproductive function in aging male and female mice. We show that, as in invertebrates, the balance of macronutrients has marked and largely opposing effects on reproductive and longevity outcomes. Mice were provided ad libitum access to one of 25 diets differing in P, C, F, and E content, with reproductive outcomes assessed at 15 months. An optimal balance of macronutrients exists for reproductive function, which, for most measures, differs from the diets that optimize lifespan, and this response differs with sex. Maximal longevity was achieved on diets containing a P:C ratio of 1:13 in males and 1:11 for females. Diets that optimized testes mass and epididymal sperm counts (indicators of gamete production) contained a higher P:C ratio (1:1) than those that maximized lifespan. In females, uterine mass (an indicator of estrogenic activity) was also greatest on high P:C diets (1:1) whereas ovarian follicle number was greatest on P:C 3:1 associated with high-F intakes. By contrast, estrous cycling was more likely in mice on lower P:C (1:8), and the number of corpora lutea, indicative of recent ovulations, was greatest on P:C similar to those supporting greatest longevity (1:11).
| S-EPMC4371964 | biostudies-literature
Project description:Selenium (Se) is an important micronutrient that, as a component of selenoproteins, influences oxidative and inflammatory processes. Its' levels vary considerably, with different ethnic and geographic population groups showing varied conditions, ranging from frank Se deficiencies to toxic effects. An optimum Se level is essential for the maintenance of homeostasis, and this optimum may vary according to life stage, general state of health, and genotype. Nutrigenetic studies of different Se levels, in the presence of genetic variants in selenoproteins, suggest that an effective dietary Se intake for one individual may be very different from that for others. However, we are just starting to learn the significance of various genes in selenoprotein pathways, functional variants in these, and how to combine such data from genes into pathways, alongside dietary intake or serum levels of Se. Advances in systems biology, genetics, and genomics technologies, including genetic/genomic, epigenetic/epigenomic, transcriptomic, proteomic, and metabolomic information, start to make it feasible to assess a comprehensive spectrum of the biological activity of Se. Such nutrigenomic approaches may prove very sensitive biomarkers of optimal Se status at the individual or population level. The premature cessation of a major human Se intervention trial has led to considerable controversy as to the value of Se supplementation at the population level. New websites provide convenient links to current information on methodologies available for nutrigenetics and nutrigenomics. These new technologies will increasingly become an essential tool in optimizing the level of Se and other micronutrients for optimal health, in individuals and in population groups. However, definitive proof of such effects will require very large collaborative studies, international agreement on study design, and innovative approaches to data analysis.
| S-EPMC3268570 | biostudies-literature