Association between polygenic propensity for psychiatric disorders and nutrient intake.

Despite the observed associations between psychiatric disorders and nutrient intake, genetic studies are limited. We examined whether polygenic scores for psychiatric disorders are associated with nutrient intake in UK Biobank (N = 163,619) using linear mixed models. We found polygenic scores for attention-deficit/hyperactivity disorder, bipolar disorder, and schizophrenia showed the highest number of associations, while a polygenic score for autism spectrum disorder showed no association. The relatively weaker obsessive-compulsive disorder polygenic score showed the greatest effect sizes suggesting its association with diet traits may become more apparent with larger genome-wide analyses. A higher alcohol dependence polygenic score was associated with higher alcohol intake and individuals with higher persistent thinness polygenic scores reported their food to weigh less, both independent of socioeconomic status. Our findings suggest that polygenic propensity for a psychiatric disorder is associated with dietary behaviour. Note, nutrient intake was self-reported and findings must therefore be interpreted mindfully.

Patients with PWS and related syndromes display differentially methylated regions involved in neurodevelopmental and nutritional trajectory.

BACKGROUND: Prader-Willi syndrome is a rare genetic neurodevelopmental disorder caused by a paternal deficiency of maternally imprinted gene expression located in the chromosome 15q11-q13 region. Previous studies have demonstrated that several classes of neurodevelopmental disorders can be attributed to either over- or under-expression of specific genes that may lead to impairments in neuronal generation, differentiation, maturation and growth. Epigenetic changes that modify gene expression have been highlighted in these disorders. One recent study focused on epigenetic analysis and compared patients with PWS with patients with other imprinting disorders. No study, however, has yet focused on epigenetics in patients with PWS specifically by comparing the mutations associated with this syndrome. OBJECTIVE: This study investigated the epigenetic modifications in patients with PWS and patients with PWS-related disorders caused by inactivation of two genes of the PWS chromosomal region, SNORD116 and MAGEL2. Our approach also aimed to compare the epigenetic modifications in PWS and PWS-related disorders. METHODS: We compared genome-wide methylation analysis (GWAS) in seven blood samples from patients with PWS phenotype (five with deletions of the PWS locus, one with a microdeletion of SNORD116 and one with a frameshift mutation of MAGEL2 presenting with Schaaf-Yang syndrome), as well as two control patients. Controls were infants that had been studied for suspicion of genetic diseases that was not confirmed by the genetic analysis and the clinical follow-up. RESULTS: The analysis identified 29,234 differentially methylated cytosines, corresponding to 5,308 differentially methylated regions (DMRs), which matched with 2,280 genes. The DMRs in patients with PWS were associated with neurodevelopmental pathways, endocrine dysfunction and social and addictive processes consistent with the key features of the PWS phenotype. In addition, the separate analysis for the SNORD116 and MAGEL2 deletions revealed that the DMRs associated with the SNORD116 microdeletion were found in genes implicated in metabolic pathways and nervous system development, whereas MAGEL2 mutations mostly concerned genes involved in macromolecule biosynthesis. CONCLUSION: The PWS is associated with epigenetic modifications with differences in SNORD116 and MAGEL2 mutations, which seem to be relevant to the different associated phenotypes.

Statistical and Machine-Learning Analyses in Nutritional Genomics Studies.

Nutritional compounds may have an influence on different OMICs levels, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics. The integration of OMICs data is challenging but may provide new knowledge to explain the mechanisms involved in the metabolism of nutrients and diseases. Traditional statistical analyses play an important role in description and data association; however, these statistical procedures are not sufficiently enough powered to interpret the large integrated multiple OMICs (multi-OMICS) datasets. Machine learning (ML) approaches can play a major role in the interpretation of multi-OMICS in nutrition research. Specifically, ML can be used for data mining, sample clustering, and classification to produce predictive models and algorithms for integration of multi-OMICs in response to dietary intake. The objective of this review was to investigate the strategies used for the analysis of multi-OMICs data in nutrition studies. Sixteen recent studies aimed to understand the association between dietary intake and multi-OMICs data are summarized. Multivariate analysis in multi-OMICs nutrition studies is used more commonly for analyses. Overall, as nutrition research incorporated multi-OMICs data, the use of novel approaches of analysis such as ML needs to complement the traditional statistical analyses to fully explain the impact of nutrition on health and disease.

Perinatal origin of adult diseases. / Origen perinatal de enfermedades del adulto.

Three relevant, interrelated scientific advances are described: the concept of critical periods (CPs), the Barker Hypothesis (BH), and the underlying epigentic mechanisms involved. Critical periods are genetically programmed, highly sensitive time intervals during which the interaction between environment and individuals generates the development of physiological processes related to physical growth and development, survival (breastfeeding), social behavior, and learning. Barker hypothesis is based on the finding that prenatal malnutrition (for example, lowbirthweight) is closely related to mortality due to cardiovascular disease CVD) in the adult, and to the risk conditions leading to it: insuline resistence, metabolic syndrome, obesity, and high blood pressure. This association is no due to genetical causes, but secondary to nutritional deficits which in turn generate epigenetic mechanisms of methylation of DNA basis and cromatine proteines (histones), which do not modify the genetic code but modulate its expresion, reinforcing some genes, inhibiting others, regulating when and where they are expressed. These genes participate in the process called programming, consisting of permanent changes in the response to stimulation of metabolic and hormone regulators, such as, for example, increasing insuline resistence. Epigenetic changes persist even when original conditions (fetal or perinatal malnutrition) are no longer present. This, in turn, affects health of the offspring later in adult life, creating thus the same environmental prenatal conditions to the next generation. This transgenerational effects of early nutritional experiences are more frequent in population groups of por socioeconomic level, and consequently have serious implications in the future health of Latin American populations.

Se describen tres adelantos interrelacionados: el concepto de períodos críticos, la hipótesis de Barker y los mecanismos epigenéticos involucrados. Los primeros son intervalos temporales genéticamente programados, vinculados a procesos fisiológicos ligados al crecimiento y desarrollo físico del individuo (habilitación de vías nerviosas, replicación neuronal), a procesos relacionados con el apego madre-hijo, la lactancia, la socialización y el aprendizaje. La hipótesis de Barker sostiene que la desnutrición, en la etapa perinatal, se asocia a mayor mortalidad por enfermedad cardiovascular y a las alteraciones metabólicas que condicionan dicha enfermedad (síndrome metabólico, resistencia a la insulina, hipertensión). Esta asociación es secundaria a las alteraciones nutricionales que desencadenan mecanismos epigenéticos de metilación de bases del ADN o de histonas. Los cambios epigenéticos son permanentes y pueden tener efectos transgeneracionales, al afectar el ambiente perinatal en donde crece la descendencia, hecho relevante en países con poblaciones que viven en condiciones socioeconómicas desfavorables.

Can we predict treatment response in children with ADHD to a vitamin-mineral supplement? An investigation into pre-treatment nutrient serum levels, MTHFR status, clinical correlates and demographic variables.

BACKGROUND: Intent-to-treat analyses from a randomized controlled trial showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement, but no group differences on clinician, parent and teacher ratings of overall ADHD symptoms. There was an advantage of micronutrients over placebo in improving overall function, emotional regulation, aggression, and reducing impairment as well as improving inattention based on clinician but not parent observation. No group differences were observed on hyperactive-impulsive symptoms. We investigated predictors of response defined by pre-treatment variables. METHOD: We conducted analyses of data from a clinical trial of children (7-12 years) with ADHD, whereby participants were randomized to receive micronutrients or placebo for 10 weeks followed by a 10 week open-label (OL) phase. We included only children who had been exposed to micronutrients for a full 10 week period and demonstrated satisfactory adherence, either in RCT phase (n = 40) or OL phase (those who received placebo during RCT phase; n = 31). Seven outcomes were examined: change in ADHD symptoms (clinician/parent), ADHD responder, overall responder, change in mood, change in functioning, and change in aggression. Demographic, developmental variables, current clinical and physical characteristics, MTHFR genotype at two common variants, and pre-treatment serum/plasma levels (vitamin D, B12, folate, zinc, copper, iron, ferritin, potassium, calcium, magnesium, and homocysteine) were all considered as putative predictors. RESULTS: Substantial nutrient deficiencies pre-treatment were observed only for vitamin D (13%) and copper (15%), otherwise most children entered the trial with nutrient levels falling within expected ranges. Regression analyses showed varying predictors across outcomes with no one predictor being consistently identified across different variables. Lower pre-treatment folate and B12 levels, being female, greater severity of symptoms and co-occurring disorders pre-treatment, more pregnancy complications and fewer birth problems were identified as possible predictors of greater improvement for some but not all outcome measures although predictive values were weak. Lower IQ and higher BMI predicted greater improvement in aggression. CONCLUSIONS: This study replicates Rucklidge et al. (2014b) showing the limited value of using serum nutrient levels to predict treatment response although we cannot rule out that other non-assayed nutrient levels may be more valuable. Additionally, no specific demographic or clinical characteristics, including MTHFR genetic status, were identified that would preclude children with ADHD from trying this treatment approach.

Eicosanoids via CYP450 and cardiovascular disease: Hints from genetic and nutrition studies.

Metabolites of arachidonic acid via CYP450 such as epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), have vasoactive and natriuretic properties and have been implicated in BP homeostasis and the incidence of cardio- and cerebrovascular diseases in animal studies. In humans, genetic studies considering genes implicated in arachidonic acids metabolism (CYP4F2, CYP4A11, CYP2J2, CYP2C8, CYP2C9, CYP2A1/2, EPHX2) can offer a hint to understand their role, if any, in hypertension development and its deleterious cardiovascular effects. Candidate genes studies and successive meta-analyses have shown that specific single nucleotide polymorphisms (SNPs), often functional, and haplotypes in these genes were associated with one or more cardiovascular endpoints. Nevertheless, genome wide association studies (GWAS) have never detected any SNPs nearby these genes (the only exception being the CYP2A1/2 locus) as associated with either BP, hypertension, coronary artery disease or stroke questioning their real importance for cardiovascular health in humans. Nutrition studies exploring the effects of specific foods on the formation of these compounds or others through the same pathway can offer new insights on this field.

Transgenerational Epigenetic Mechanisms in Adipose Tissue Development.

An adverse nutritional environment during the perinatal period increases the risk of adult-onset metabolic diseases, such as obesity, which may persist across generations. Adipose tissue (AT) from offspring of malnourished dams has been shown to display altered adipogenesis, lipogenesis, and adipokine expression, impaired thermogenesis, and low-grade inflammation. Although the exact mechanisms underlying these alterations remain unclear, epigenetic processes are believed to have an important role. In this review, we focus on epigenetic mechanisms in AT that may account for transgenerational dysregulation of adipocyte formation and adipose function. Understanding the complex interactions between maternal diet and epigenetic regulation of the AT in offspring may be valuable in improving preventive strategies against the obesity pandemic.

Emerging concepts on the role of epigenetics in the relationships between nutrition and health.

Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet-related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life-long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one-carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age-related chronic disease. Revealing diet-epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life-long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet-pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled 'Nutrition, Epigenetics, Genetics: Impact on Health and Disease'. For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.

Dietary Modulation of the Epigenome.

Epigenetics is the study of heritable mechanisms that can modify gene activity and phenotype without modifying the genetic code. The basis for the concept of epigenetics originated more than 2,000 yr ago as a theory to explain organismal development. However, the definition of epigenetics continues to evolve as we identify more of the components that make up the epigenome and dissect the complex manner by which they regulate and are regulated by cellular functions. A substantial and growing body of research shows that nutrition plays a significant role in regulating the epigenome. Here, we critically assess this diverse body of evidence elucidating the role of nutrition in modulating the epigenome and summarize the impact such changes have on molecular and physiological outcomes with regards to human health.

[Cancer and nutrition - a paradigma shift]. / Krebs und Ernährung ­ ein Paradigmenwechsel.

Substantial international differences in the prevalence of cancer disease suppose that nutrition may be an important factor in the development of cancer. Many experts believe, that nutritional factors may contribute up to 35 % to the development of malignant tumors. Many patients have lost substantial body weight already at the time of the diagnosis of the disease as consequence of undernutrition and malnutrition, respectively. During the course of the disease the nutritional status often is deteriorating further. Caused by both the cancer disease itself and the treatment, loss of appetite, changes in taste, nausea and vomiting may additionally contribute to undernutrition. Undernutrition is a relevant factor for the outcome of the disease and for the tolerance of the treatment as well. Therefore, supporting the heavily impaired patients in nutritional intake is of paramount importance and an urgent task for physicians and nurses. In view of physiology, pathophysiology, genetics and molecular biology, metabolic processes in cancer are highly complex regulated and there is increasing evidence that a diet rich in fat and protein is favourable. This, however, implies a paradigma shift away from the "healthy" balanced diet rich in fruit, vegetable and complex carbohydrates. So far, the evidence based data of this new concept is, however, a controversial issue.

Characterization of the serum and liver proteomes in gut-microbiota-lacking mice.

Current nutrition research is focusing on health promotion, disease prevention, and performance improvement for individuals and communities around the world. The humans with required nutritional ingredients depend on both how well the individual is provided with balanced foods and what state of gut microbiota the host has. Studying the mutually beneficial relationships between gut microbiome and host is an increasing attention in biomedical science. The purpose of this study is to understand the role of gut microbiota and to study interactions between gut microbiota and host. In this study, we used a shotgun proteomic approach to reveal the serum and liver proteomes in gut-microbiota-lacking mice. For serum, 15 and 8 proteins were uniquely detected in specific-pathogen-free (SPF) and germ-free (GF) mice, respectively, as well as the 3 and 20 proteins were significantly increased and decreased, respectively, in GF mice compared to SPF mice. Among the proteins of the serum, major urinary protein 1 (MUP-1) of GF mice was significantly decreased compared to SPF mice. In addition, MUP-1 expression is primarily regulated by testosterone. Lacking in gut flora has been implicated in many adverse effects, and now we have found its pathogenic root maybe gut bacteria can regulate the sex-hormone testosterone levels. In the liver, 8 and 22 proteins were uniquely detected in GF mice and SPF mice, respectively, as well as the 14 and 30 proteins were significantly increased and decreased, respectively, in GF mice compared to SPF mice. Furthermore, ingenuity pathway analysis (IPA) indicated that gut microbiota influence the host in cancer, organismal injury and abnormalities, respiratory disease; cell cycle, cellular movement and tissue development; cardiovascular disease, reproductive system disease; and lipid metabolism, molecular transport and small molecule biochemistry. Our findings provide more detailed information of the role of gut microbiota and will be useful to help study gut bacteria and disease prevention.

Seasonal variations of U.S. mortality rates: Roles of solar ultraviolet-B doses, vitamin D, gene exp ression, and infections.

Death rates in the U.S. show a pronounced seasonality. The broad seasonal variation shows about 25% higher death rates in winter than in summer with an additional few percent increase associated with the Christmas and New Year's holidays. A pronounced increase in death rates also starts in mid-September, shortly after the school year begins. The causes of death with large contributions to the observed seasonality include diseases of the circulatory system; the respiratory system; the digestive system; and endocrine, nutritional, and metabolic diseases. Researchers have identified several factors showing seasonal variation that could possibly explain the seasonal variations in mortality rate. These factors include seasonal variations in solar ultraviolet-B(UVB) doses and serum 25-hydroxyvitamin D [25(OH)D] concentrations, gene expression, ambient temperature and humidity, UVB effects on environmental pathogen load, environmental pollutants and allergens, and photoperiod (or length of day). The factors with the strongest support in this analysis are seasonal variations in solar UVB doses and 25(OH)D concentrations. In the U.S., population mean 25(OH)D concentrations range from 21ng/mL in March to 28ng/mL in August. Measures to ensure that all people had 25(OH)D concentrations >36ng/mL year round would probably reduce death rates significantly.

The comet assay as a tool for human biomonitoring studies: the ComNet project.

The comet assay is widely used in human biomonitoring to measure DNA damage as a marker of exposure to genotoxic agents or to investigate genoprotective effects. Studies often involve small numbers of subjects, and design may be sub-optimal in other respects. In addition, comet assay protocols in use in different laboratories vary significantly. In spite of these difficulties, it is appropriate to carry out a pooled analysis of all available comet assay biomonitoring data, in order to establish baseline parameters of DNA damage, and to investigate associations between comet assay measurements and factors such as sex, age, smoking status, nutrition, lifestyle, etc. With this as its major objective, the ComNet project has recruited almost 100 research groups willing to share datasets. Here we provide a background to this project, discussing the history of the comet assay and practical issues that can critically affect its performance. We survey its diverse applications in biomonitoring studies, including environmental and occupational exposure to genotoxic agents, genoprotection by dietary and other factors, DNA damage associated with various diseases, and intrinsic factors that affect DNA damage levels in humans. We examine in depth the quality of data from a random selection of studies, from an epidemiological and statistical point of view.

Pancreatic islets and their roles in metabolic programming.

Experimental and epidemiologic data have confirmed that undernutrition or overnutrition during critical periods of life can result in metabolic dysfunction, leading to the development of obesity, hypertension, and type 2 diabetes, later in life. These studies have contributed to the concept of the developmental origins of health and disease (DOHaD), which involves metabolic programming patterns. Beyond the earlier phases of development, puberty can be an additional period of plasticity, during which any insult can lead to changes in metabolism. Impaired brain development, associated with imbalanced autonomous nervous system activity due to metabolic programming, is pivotal to the creation of pathophysiology. Excess glucocorticoid exposure, due to hypothalamic-pituitary-adrenal axis deregulation, is also involved in malprogramming in early life. Additionally, the pancreatic islets appear to play a decisive role in the setup and maintenance of these metabolic dysfunctions as key targets of metabolic programming, and epigenetic mechanisms may underlie these changes. Moreover, studies have indicated the possibility that deprogramming renders the islets able to recover their functioning after malprogramming. In this review, we discuss the key roles of the pancreatic islets as targets of malprogramming; however, we also discuss their roles as important targets for the treatment and prevention of metabolic diseases.

The role of ghrelin in weight-regulation disorders: implications in clinical practice.

Ghrelin, an orexigenic protein with a unique lipid chain modification, is considered to be an important gut-brain signal for appetite control and energy balance. The ghrelin receptor, growth-hormone secretagogue receptor type 1a, is able to bind acylated ghrelin. The first recognised effect of ghrelin was the induction of growth hormone release from the somatotroph cells of the anterior pituitary. Moreover, by acting on vagal afferents or centrally, ghrelin can activate hypothalamic arcuate neurons that secrete the orexigenic peptides neuropeptide Y and agouti-related peptide, and inhibit the anorexigenic neurons secreting pro-opiomelanocortin and α-melanocyte-stimulating hormone. The orexigenic signalling pathway of ghrelin involves adenosine monophosphate-activated protein kinase. It has been proposed that ghrelin can also increase dopaminergic transmission from the ventral tegmental area to the nucleus accumbens, leading to augmentation of afferent reward signals. Present evidence suggests that ghrelin plays an important role in obesity, eating disorders, and cachexia, as well as in regulating appetite and energy balance in healthy individuals. In pathological states, ghrelin can be lower than normal as is seen in obese individuals, or can be higher than normal as has been reported for Prader-Willi syndrome, anorexia nervosa, bulimia nervosa, and certain types of cachexia. In the future, the application of compounds targeting the ghrelin pathway could involve the use of pharmacotherapies of ghrelin agonists, antagonists or inverse agonists, neutralisation of ghrelin by vaccines and spiegelmers, desacyl ghrelin analogues, as well as inhibitors of the GOAT enzyme which attaches the lipid modification to desacyl ghrelin to synthetise ghrelin.

[Vitamin D in childhood]. / La vitamine D en pédiatrie.

Infantile Nutritional Rickets has disappeared almost completely in France since 1992 as vitamin D enriched formula availability and previous vitamin D supplementation of infants. The search of evocative symptoms of rickets should be a routine procedure in infants, in particular in case of insufficient vitamin D intake i.e. breastfeeding, and the possibility of vitamin D resistant rickets. Hypocalcaemia occurs not only at the first but also the advanced stages of vitamin D deficiency, and may be responsible for severe cardiologic, neurologic or respiratory complications with possibility of infant death. For the young children between 1 and 5 years and for adolescents, vitamin D insufficiency is responsible for poor skeletal mineralization, loss of bone strength, and a reduction of peak of bone mineral mass at the end of puberty. The new Dietary Reference Intakes (DRI, 2011) increased greatly the Recommended Dietary allowances (RDA) from 200 to 600 IU/d (15 µg/d) for individuals from 1 to 70 years of age. These levels are not reached in winter, even in countries, like USA and Canada, where vitamin D milk fortification is mandatory and others like Japan and North-European countries despite high fish consumption. From 1 to 5 years of age and during adolescence, a winter vitamin D3 supplementation is necessary with 80.000 or 100.000 IU periodic loads every 3 months i.e. in November and February. In cases of an underlying risk, i.e. insufficient vitamin D photosynthesis in summertime (dark skin, wearing heavily skin-covering clothes, or several skin diseases), or digestive, renal or nutritional pathologies, use of some drugs, loading dose of 80.000 or 100.000 IU, every 3 months should be administered over the year.

Insulin-like growth factor-I (IGF-I) and clinical nutrition.

IGF-I (insulin-like growth factor-I) is a peptide hormone, produced predominantly by the liver in response to pituitary GH (growth hormone), which is involved in a wide variety of physiological processes. It acts in an endocrine, paracrine and autocrine manner to promote growth. The production of IGF-I signals the availability of nutrients needed for its anabolic actions. Recently, there has been growing interest in its role in health and disease. IGF-I has long been known to be regulated by nutrition and dysregulated in states of under- and over-nutrition, its serum concentrations falling in malnutrition and responding promptly to refeeding. This has led to interest in its utility as a nutritional biomarker. A considerable evidence base supports utility for measurement of IGF-I in nutritional contexts. Its concentration may be valuable in providing information on nutritional status, prognosis and in monitoring nutritional support. However, it is insufficiently specific for use as a screening test for under nutrition as its serum concentration is influenced by many factors other than nutritional status, notably the APR (acute-phase response) and endocrine conditions. Concentrations should be interpreted along with clinical findings and the results of other investigations such as CRP (C-reactive protein). More recently, there has been interest in free IGF-I which holds promise as a nutritional marker. The present review covers nutritional regulation of IGF-I and its dysregulation in disease, then goes on to review recent studies supporting its utility as a nutritional marker in clinical contexts. Although not currently recommended by clinical guidelines, it is likely that, in time, measurement of IGF-I will become a routine part of nutritional assessment in a number of these contexts.

Genomic and epigenomic insights into nutrition and brain disorders.

Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer's disease, schizophrenia, Parkinson's disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders.

Fitness, nutrition and the molecular basis of chronic disease.

The onset of chronic disease is often the prelude to the subsequent physiological and mental twilight in the aging population of modern society. While rates of obesity, specific types of cancer and cardiovascular disorders seem to be on the rise in this group, many new therapies have addressed diseases that have been largely untreatable in the past. Alzheimer's disease has also recently come to the forefront of ongoing maladies most typically associated with an aging population. Ironically, though, many people seem to be living longer than expected. Recent biochemical, nutritional and genomic approaches have been able to elucidate some of the complex mechanisms, which lead to chronic diseases associated with an aging population such as Alzheimer's, metabolic syndrome, tumor metastasis and cardiovascular disease. These diseases and their sequalae seem to be related in many respects, with the common culprit being the inflammatory environment created by the presence of excess fat - particularly within the vascular network. Although a substantial effort has been focused on the development of new-line therapeutics to address these issues, nutrition and overall fitness and their effects on stalling or potentially reversing the advent of these diseases has not been fully embraced in the research arena. This review discusses the role of the inflammatory environment in the development of chronic diseases in the aging population and also proposes a common pathology. The benefits that improvements and dedication in nutrition and fitness approaches may offer at the molecular level are also discussed.