1 5586 96 ROLE OF PERSONALIZED NUTRITION IN CHRONIC-DEGENERATIVE DISEASES. HUMAN NUTRITION IS A BRANCH OF MEDICINE BASED ON FOODS BIOCHEMICAL INTERACTIONS WITH THE HUMAN BODY. THE PHENOTYPIC TRANSITION FROM HEALTH TO DISEASE STATUS CAN BE ATTRIBUTED TO CHANGES IN GENES AND/OR PROTEIN EXPRESSION. FOR THIS REASON, A NEW DISCIPLINE HAS BEEN DEVELOPED CALLED "-OMIC SCIENCE". IN THIS REVIEW, WE ANALYZED THE ROLE OF "-OMICS SCIENCES" (NUTRIGENETICS, NUTRIGENOMICS, PROTEOMICS AND METABOLOMICS) IN THE HEALTH STATUS AND AS POSSIBLE THERAPEUTIC TOOL IN CHRONIC DEGENERATIVE DISEASES. IN PARTICULAR, WE FOCUSED ON THE ROLE OF NUTRIGENETICS AND THE RELATIONSHIP BETWEEN EATING HABITS, CHANGES IN THE DNA SEQUENCE AND THE ONSET OF NUTRITION-RELATED DISEASES. MOREOVER, WE EXAMINED NUTRIGENOMICS AND THE EFFECT OF NUTRIENTS ON GENE EXPRESSION. WE PERUSED THE ROLE OF PROTEOMICS AND METABOLOMICS IN PERSONALIZED NUTRITION. IN THIS SCENARIO, WE ANALYZED ALSO HOW DYSBIOSIS OF GUT MICROBIOTA CAN INFLUENCE THE ONSET AND PROGRESSION OF CHRONIC DEGENERATIVE DISEASES. MOREOVER, NUTRIENTS INFLUENCING AND REGULATING GENE ACTIVITY, BOTH DIRECTLY AND INDIRECTLY, PAVES THE WAY FOR PERSONALIZED NUTRITION THAT PLAYS A KEY ROLE IN THE PREVENTION AND TREATMENT OF CHRONIC DEGENERATIVE DISEASES. 2019 2 2930 36 GENES AND DIET IN THE PREVENTION OF CHRONIC DISEASES IN FUTURE GENERATIONS. NUTRITION IS A MODIFIABLE KEY FACTOR THAT IS ABLE TO INTERACT WITH BOTH THE GENOME AND EPIGENOME TO INFLUENCE HUMAN HEALTH AND FERTILITY. IN PARTICULAR, SPECIFIC GENETIC VARIANTS CAN INFLUENCE THE RESPONSE TO DIETARY COMPONENTS AND NUTRIENT REQUIREMENTS, AND CONVERSELY, THE DIET ITSELF IS ABLE TO MODULATE GENE EXPRESSION. IN THIS CONTEXT AND THE ERA OF PRECISION MEDICINE, NUTRIGENETIC AND NUTRIGENOMIC STUDIES OFFER SIGNIFICANT OPPORTUNITIES TO IMPROVE THE PREVENTION OF METABOLIC DISTURBANCES, SUCH AS TYPE 2 DIABETES, GESTATIONAL DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASES, EVEN WITH TRANSGENERATIONAL EFFECTS. THE PRESENT REVIEW TAKES INTO ACCOUNT THE INTERACTIONS BETWEEN DIET, GENES AND HUMAN HEALTH, AND PROVIDES AN OVERVIEW OF THE ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. MOREOVER, WE FOCUS OUR ATTENTION ON THE MECHANISM OF INTERGENERATIONAL OR TRANSGENERATIONAL TRANSMISSION OF THE SUSCEPTIBILITY TO METABOLIC DISTURBANCES, AND UNDERLINE THAT THE REVERSIBILITY OF EPIGENETIC MODIFICATIONS THROUGH DIETARY INTERVENTION COULD COUNTERACT PERTURBATIONS INDUCED BY LIFESTYLE AND ENVIRONMENTAL FACTORS. 2020 3 4794 25 NUTRITIONAL GENOMIC APPROACHES TO CANCER PREVENTION RESEARCH. A WEALTH OF EVIDENCE POINTS TO THE DIET AS ONE OF THE MOST IMPORTANT MODIFIABLE DETERMINANTS OF THE RISK OF DEVELOPING CANCER, BUT A GREATER UNDERSTANDING OF THE INTERACTION BETWEEN DIET AND GENES MAY HELP DISTINGUISH WHO WILL AND WILL NOT RESPOND TO DIETARY INTERVENTIONS. THE TERM NUTRIGENOMICS OR NUTRITIONAL GENOMICS REFERS TO THE BIDIRECTIONAL INTERACTIONS BETWEEN GENES AND DIET. NUTRITIONAL GENOMICS ENCOMPASSES AN UNDERSTANDING ABOUT HOW THE RESPONSE TO BIOACTIVE FOOD COMPONENTS DEPENDS ON AN INDIVIDUAL'S GENETIC BACKGROUND (NUTRIGENETICS), NUTRIENT INDUCED CHANGES IN DNA METHYLATION, HISTONE POSTTRANSLATIONAL MODIFICATIONS, AND OTHER CHROMATIN ALTERATIONS (NUTRITIONAL EPIGENETICS), AND NUTRIENT INDUCED CHANGES IN GENE EXPRESSION (NUTRITIONAL TRANSCRIPTOMICS). THESE APPROACHES TO THE STUDY OF NUTRITION WILL ASSIST IN UNDERSTANDING HOW GENETIC VARIATION, EPIGENETIC EVENTS, AND REGULATION OF GENE EXPRESSION ALTER REQUIREMENTS FOR, AND RESPONSES TO, NUTRIENTS. RECOGNITION OF THE INTERPLAY BETWEEN GENES AND DIET COULD ULTIMATELY HELP IDENTIFY MODIFIABLE MOLECULAR TARGETS FOR PREVENTING, DELAYING, OR REDUCING THE SYMPTOMS OF CANCER AND OTHER CHRONIC DISEASES. 2007 4 6858 22 [NUTRIGENOMICS, OBESITY AND PUBLIC HEALTH]. FUNCTIONAL GENOMICS WILL CHANGE KNOWLEDGE AND PRACTICE IN CLINICAL NUTRITION IN THE FORTHCOMING YEARS. THE POSSIBILITY OF PERFORMING AN INDIVIDUAL'S GENETIC PROFILE (GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS) AS WELL AS THE ABILITY OF ITS INTEGRATION IN A COMPLEX NETWORK OF METABOLIC INTERACTIONS REPRESENTS A HUGE CHALLENGE IN HUMAN NUTRITION. THE INFLUENCE OF NUTRIGENOMICS IN TERMS OF PREVENTION AND TREATMENT OF CHRONIC DISEASES, SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE IN A POPULATION LEVEL REMAINS UNDETERMINED FOR THE MOMENT. THE OPPORTUNITY OF NUTRITIONAL INTERVENTION IN CRITICAL STAGES OF DEVELOPMENT AND THE CHANCE OF CHANGING GENETIC SUSCEPTIBILITY TO DISEASES THROUGH DIET IN A PUBLIC HEALTH BASIS SHOULD LEAD THE FUTURE OF NUTRIGENOMICS BEYOND THE MERE DESIGN OF "PERSONALIZED" FUNCTIONAL FOOD OR DIETS. 2007 5 3169 37 GUIDE FOR CURRENT NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC APPROACHES FOR PRECISION NUTRITION INVOLVING THE PREVENTION AND MANAGEMENT OF CHRONIC DISEASES ASSOCIATED WITH OBESITY. CHRONIC DISEASES, INCLUDING OBESITY, ARE MAJOR CAUSES OF MORBIDITY AND MORTALITY IN MOST COUNTRIES. THE ADVERSE IMPACTS OF OBESITY AND ASSOCIATED COMORBIDITIES ON HEALTH REMAIN A MAJOR CONCERN DUE TO THE LACK OF EFFECTIVE INTERVENTIONS FOR PREVENTION AND MANAGEMENT. PRECISION NUTRITION IS AN EMERGING THERAPEUTIC APPROACH THAT TAKES INTO ACCOUNT AN INDIVIDUAL'S GENETIC AND EPIGENETIC INFORMATION, AS WELL AS AGE, GENDER, OR PARTICULAR PHYSIOPATHOLOGICAL STATUS. ADVANCES IN GENOMIC SCIENCES ARE CONTRIBUTING TO A BETTER UNDERSTANDING OF THE ROLE OF GENETIC VARIANTS AND EPIGENETIC SIGNATURES AS WELL AS GENE EXPRESSION PATTERNS IN THE DEVELOPMENT OF DIVERSE CHRONIC CONDITIONS, AND HOW THEY MAY MODIFY THERAPEUTIC RESPONSES. THIS KNOWLEDGE HAS LED TO THE SEARCH FOR GENETIC AND EPIGENETIC BIOMARKERS TO PREDICT THE RISK OF DEVELOPING CHRONIC DISEASES AND PERSONALIZING THEIR PREVENTION AND TREATMENT. ADDITIONALLY, ORIGINAL NUTRITIONAL INTERVENTIONS BASED ON NUTRIENTS AND BIOACTIVE DIETARY COMPOUNDS THAT CAN MODIFY EPIGENETIC MARKS AND GENE EXPRESSION HAVE BEEN IMPLEMENTED. ALTHOUGH CAUTION MUST BE EXERCISED, THESE SCIENTIFIC INSIGHTS ARE PAVING THE WAY FOR THE DESIGN OF INNOVATIVE STRATEGIES FOR THE CONTROL OF CHRONIC DISEASES ACCOMPANYING OBESITY. THIS DOCUMENT PROVIDES A NUMBER OF EXAMPLES OF THE HUGE POTENTIAL OF UNDERSTANDING NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC ROLES IN PRECISION NUTRITION. 2017 6 6379 33 THE ROLE OF NUTRITION ON META-INFLAMMATION: INSIGHTS AND POTENTIAL TARGETS IN COMMUNICABLE AND CHRONIC DISEASE MANAGEMENT. PURPOSE OF REVIEW: CHRONIC LOW-GRADE INFLAMMATION MAY CONTRIBUTE TO THE ONSET AND PROGRESSION OF COMMUNICABLE AND CHRONIC DISEASES. THIS REVIEW EXAMINED THE EFFECTS AND EVENTUAL MEDIATION ROLES OF DIFFERENT NUTRITIONAL FACTORS ON INFLAMMATION. RECENT FINDINGS: POTENTIAL NUTRITIONAL COMPOUNDS INFLUENCING INFLAMMATION PROCESSES INCLUDE MACRO AND MICRONUTRIENTS, BIOACTIVE MOLECULES (POLYPHENOLS), SPECIFIC FOOD COMPONENTS, AND CULINARY INGREDIENTS AS WELL AS STANDARDIZED DIETARY PATTERNS, EATING HABITS, AND CHRONONUTRITION FEATURES. THEREFORE, RESEARCH IN THIS FIELD IS STILL REQUIRED, TAKING INTO ACCOUNT CRITICAL ASPECTS OF HETEROGENEITY INCLUDING TYPE OF POPULATION, MINIMUM AND MAXIMUM INTAKES AND ADVERSE EFFECTS, COOKING METHODS, PHYSIOPATHOLOGICAL STATUS, AND TIMES OF INTERVENTION. MOREOVER, THE INTEGRATIVE ANALYSIS OF TRADITIONAL VARIABLES (AGE, SEX, METABOLIC PROFILE, CLINICAL HISTORY, BODY PHENOTYPE, HABITUAL DIETARY INTAKE, PHYSICAL ACTIVITY LEVELS, AND LIFESTYLE) TOGETHER WITH INDIVIDUALIZED ISSUES (GENETIC BACKGROUND, EPIGENETIC SIGNATURES, MICROBIOTA COMPOSITION, GENE EXPRESSION PROFILES, AND METABOLOMIC FINGERPRINTS) MAY CONTRIBUTE TO THE KNOWLEDGE AND PRESCRIPTION OF MORE PERSONALIZED TREATMENTS AIMED TO IMPROVING THE PRECISION MEDICAL MANAGEMENT OF INFLAMMATION AS WELL AS THE DESIGN OF ANTI-INFLAMMATORY DIETS IN CHRONIC AND COMMUNICABLE DISEASES. 2022 7 6204 34 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 8 2855 41 FROM INFLAMMAGING TO HEALTHY AGING BY DIETARY LIFESTYLE CHOICES: IS EPIGENETICS THE KEY TO PERSONALIZED NUTRITION? THE PROGRESSIVELY OLDER POPULATION IN DEVELOPED COUNTRIES IS REFLECTED IN AN INCREASE IN THE NUMBER OF PEOPLE SUFFERING FROM AGE-RELATED CHRONIC INFLAMMATORY DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, HEART AND LUNG DISEASES, CANCER, OSTEOPOROSIS, ARTHRITIS, AND DEMENTIA. THE HETEROGENEITY IN BIOLOGICAL AGING, CHRONOLOGICAL AGE, AND AGING-ASSOCIATED DISORDERS IN HUMANS HAVE BEEN ASCRIBED TO DIFFERENT GENETIC AND ENVIRONMENTAL FACTORS (I.E., DIET, POLLUTION, STRESS) THAT ARE CLOSELY LINKED TO SOCIOECONOMIC FACTORS. THE COMMON DENOMINATOR OF THESE FACTORS IS THE INFLAMMATORY RESPONSE. CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION DURING PHYSIOLOGICAL AGING AND IMMUNOSENESCENCE ARE INTERTWINED IN THE PATHOGENESIS OF PREMATURE AGING ALSO DEFINED AS 'INFLAMMAGING.' THE LATTER HAS BEEN ASSOCIATED WITH FRAILTY, MORBIDITY, AND MORTALITY IN ELDERLY SUBJECTS. HOWEVER, IT IS UNKNOWN TO WHAT EXTENT INFLAMMAGING OR LONGEVITY IS CONTROLLED BY EPIGENETIC EVENTS IN EARLY LIFE. TODAY, HUMAN DIET IS BELIEVED TO HAVE A MAJOR INFLUENCE ON BOTH THE DEVELOPMENT AND PREVENTION OF AGE-RELATED DISEASES. MOST PLANT-DERIVED DIETARY PHYTOCHEMICALS AND MACRO- AND MICRONUTRIENTS MODULATE OXIDATIVE STRESS AND INFLAMMATORY SIGNALING AND REGULATE METABOLIC PATHWAYS AND BIOENERGETICS THAT CAN BE TRANSLATED INTO STABLE EPIGENETIC PATTERNS OF GENE EXPRESSION. THEREFORE, DIET INTERVENTIONS DESIGNED FOR HEALTHY AGING HAVE BECOME A HOT TOPIC IN NUTRITIONAL EPIGENOMIC RESEARCH. INCREASING EVIDENCE HAS REVEALED THAT COMPLEX INTERACTIONS BETWEEN FOOD COMPONENTS AND HISTONE MODIFICATIONS, DNA METHYLATION, NON-CODING RNA EXPRESSION, AND CHROMATIN REMODELING FACTORS INFLUENCE THE INFLAMMAGING PHENOTYPE AND AS SUCH MAY PROTECT OR PREDISPOSE AN INDIVIDUAL TO MANY AGE-RELATED DISEASES. REMARKABLY, HUMANS PRESENT A BROAD RANGE OF RESPONSES TO SIMILAR DIETARY CHALLENGES DUE TO BOTH GENETIC AND EPIGENETIC MODULATIONS OF THE EXPRESSION OF TARGET PROTEINS AND KEY GENES INVOLVED IN THE METABOLISM AND DISTRIBUTION OF THE DIETARY CONSTITUENTS. HERE, WE WILL SUMMARIZE THE EPIGENETIC ACTIONS OF DIETARY COMPONENTS, INCLUDING PHYTOCHEMICALS, AND MACRO- AND MICRONUTRIENTS AS WELL AS METABOLITES, THAT CAN ATTENUATE INFLAMMAGING. WE WILL DISCUSS THE CHALLENGES FACING PERSONALIZED NUTRITION TO TRANSLATE HIGHLY VARIABLE INTERINDIVIDUAL EPIGENETIC DIET RESPONSES TO POTENTIAL INDIVIDUAL HEALTH BENEFITS/RISKS RELATED TO AGING DISEASE. 2015 9 5069 28 PHYSICAL ACTIVITY IN THE PREVENTION OF HUMAN DISEASES: ROLE OF EPIGENETIC MODIFICATIONS. EPIGENETIC MODIFICATION REFERS TO HERITABLE CHANGES IN GENE FUNCTION THAT CANNOT BE EXPLAINED BY ALTERATIONS IN THE DNA SEQUENCE. THE CURRENT LITERATURE CLEARLY DEMONSTRATES THAT THE EPIGENETIC RESPONSE IS HIGHLY DYNAMIC AND INFLUENCED BY DIFFERENT BIOLOGICAL AND ENVIRONMENTAL FACTORS SUCH AS AGING, NUTRIENT AVAILABILITY AND PHYSICAL EXERCISE. AS SUCH, IT IS WELL ACCEPTED THAT PHYSICAL ACTIVITY AND EXERCISE CAN MODULATE GENE EXPRESSION THROUGH EPIGENETIC ALTERNATIONS ALTHOUGH THE TYPE AND DURATION OF EXERCISE ELICITING SPECIFIC EPIGENETIC EFFECTS THAT CAN RESULT IN HEALTH BENEFITS AND PREVENT CHRONIC DISEASES REMAINS TO BE DETERMINED. THIS REVIEW HIGHLIGHTS THE MOST SIGNIFICANT FINDINGS FROM EPIGENETIC STUDIES INVOLVING PHYSICAL ACTIVITY/EXERCISE INTERVENTIONS KNOWN TO BENEFIT CHRONIC DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, CANCER, CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. 2017 10 6454 47 THIRD JESUS CULEBRAS LECTURE - MOLECULAR BIOLOGY AND CLINICAL NUTRITION; WHERE DO WE STAND AND WHERE DO WE GO? NUTRITION PLAYS A FUNDAMENTAL ROLE IN THE MAINTENANCE OF HEALTH AND THE TREATMENT OF DISEASE, AND SERVES AS THE CROSSROADS FOR MANY DISCIPLINES. BIOCHEMISTRY AND MOLECULAR BIOLOGY REPRESENTS A KEY BRAND OF SCIENCE TO ASCERTAIN THE MECHANISM OF ACTION OF NUTRIENTS AND OTHER FOOD BIOACTIVE COMPOUNDS IN HEALTH AND DISEASE. THE AIM OF THE PRESENT JESUS M. CULEBRAS LECTURE IS TO CONSIDER THE FUTURE OF THE RELATIONSHIPS BETWEEN MOLECULAR BIOLOGY AND CLINICAL NUTRITION AND TO DISCUSS THE USE OF MOLECULAR AND GENETIC TOOLS TO STUDY MOLECULAR RESPONSES TO DIETARY FACTORS AND THE METABOLIC CONSEQUENCES OF FOOD AND TO CONSIDER MAJOR CHALLENGES ON HUMAN NUTRITION SCIENCES IN THE 21(ST) CENTURY. PARTICULAR EMPHASIS IS GIVEN TO THE IDENTIFICATION AND USE OF NOVEL BIOMARKERS IN INFLAMMATORY DISEASES. LIKEWISE, THE IMPORTANCE OF THE HUMAN MICROBIOME AND HOW MICROORGANISMS CAN BE SAFELY UTILIZED IN THE PREVENTION AND MANAGEMENT OF INFECTIOUS AND CHRONIC DISEASES ARE DISCUSSED. MOREOVER, THE KEY ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE NEW ERA OF NUTRITION IS CONSIDERED. NUTRIGENETICS REFERS TO THE ROLE OF DNA SEQUENCE VARIATION IN THE RESPONSES TO NUTRIENTS, WHEREAS NUTRIGENOMICS IS THE STUDY OF THE ROLE OF NUTRIENTS IN GENE EXPRESSION. EPIGENETICS IS THE STUDY OF MITOTICALLY HERITABLE ALTERATIONS IN GENE EXPRESSION POTENTIAL THAT ARE NOT CAUSED BY DNA SEQUENCE ALTERATIONS. IN THE PAST DECADE, IT HAS INCREASINGLY BEEN RECOGNIZED THAT DYSREGULATION OF EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN HUMAN DISEASE. INDEED, THERE IS INCREASING INTEREST IN EPIGENETIC MECHANISMS UNDERLYING PHENOTYPE MODIFICATION MODULATED BY NUTRIENTS. FURTHER RESEARCH IN THOSE AREAS SHOULD CONTRIBUTE TO EVALUATE FUNCTIONALITY OF SPECIFIC NUTRIENTS AND BIOACTIVE COMPOUNDS IN CLINICAL NUTRITION AND ALLOW PERSONALIZED NUTRITIONAL ADVICE. 2013 11 6378 35 THE ROLE OF NUTRITION ON EPIGENETIC MODIFICATIONS AND THEIR IMPLICATIONS ON HEALTH. NUTRITION PLAYS A KEY ROLE IN MANY ASPECTS OF HEALTH AND DIETARY IMBALANCES ARE MAJOR DETERMINANTS OF CHRONIC DISEASES INCLUDING CARDIOVASCULAR DISEASE, OBESITY, DIABETES AND CANCER. ADEQUATE NUTRITION IS PARTICULARLY ESSENTIAL DURING CRITICAL PERIODS IN EARLY LIFE (BOTH PRE- AND POSTNATAL). IN THIS REGARD, THERE IS EXTENSIVE EPIDEMIOLOGIC AND EXPERIMENTAL DATA SHOWING THAT EARLY SUB-OPTIMAL NUTRITION CAN HAVE HEALTH CONSEQUENCES SEVERAL DECADES LATER. THE HYPOTHESIS THAT EPIGENETIC MECHANISMS MAY LINK SUCH NUTRITIONAL IMBALANCES WITH ALTERED DISEASE RISK HAS BEEN GAINING ACCEPTANCE OVER RECENT YEARS. EPIGENETICS CAN BE DEFINED AS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION THAT DO NOT INVOLVE ALTERATIONS IN THE DNA SEQUENCE. EPIGENETIC MARKS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND A VARIETY OF NON-CODING RNAS. STRIKINGLY, THEY ARE PLASTIC AND RESPOND TO ENVIRONMENTAL SIGNALS, INCLUDING DIET. HERE WE WILL REVIEW HOW DIETARY FACTORS MODULATE THE ESTABLISHMENT AND MAINTENANCE OF EPIGENETIC MARKS, THEREBY INFLUENCING GENE EXPRESSION AND, HENCE, DISEASE RISK AND HEALTH. 2012 12 3404 33 HOW EPIGENETICS IMPACTS ON HUMAN DISEASES. EPIGENETICS IS A RAPIDLY GROWING FIELD OF BIOLOGY THAT STUDIES THE CHANGES IN GENE EXPRESSION THAT ARE NOT DUE TO ALTERATIONS IN THE DNA SEQUENCE BUT RATHER THE CHEMICAL MODIFICATIONS OF DNA AND ITS ASSOCIATED PROTEINS. EPIGENETIC MECHANISMS CAN PROFOUNDLY INFLUENCE GENE EXPRESSION, CELL DIFFERENTIATION, TISSUE DEVELOPMENT, AND DISEASE SUSCEPTIBILITY. UNDERSTANDING EPIGENETIC CHANGES IS ESSENTIAL TO ELUCIDATE THE MECHANISMS UNDERLYING THE INCREASINGLY RECOGNIZED ROLE OF ENVIRONMENTAL AND LIFESTYLE FACTORS IN HEALTH AND DISEASE AND THE INTERGENERATIONAL TRANSMISSION OF PHENOTYPES. RECENT STUDIES SUGGEST EPIGENETICS MAY BE CRITICAL IN VARIOUS DISEASES, FROM CARDIOVASCULAR DISEASE AND CANCER TO NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. EPIGENETIC MODIFICATIONS ARE POTENTIALLY REVERSIBLE AND COULD PROVIDE NEW THERAPEUTIC AVENUES FOR TREATING THESE DISEASES USING EPIGENETIC MODULATORS. MOREOVER, EPIGENETICS PROVIDE INSIGHT INTO DISEASE PATHOGENESIS AND BIOMARKERS FOR DISEASE DIAGNOSIS AND RISK STRATIFICATION. NEVERTHELESS, EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL FOR UNINTENDED CONSEQUENCES AND MAY POTENTIALLY LEAD TO INCREASED RISKS OF UNEXPECTED OUTCOMES, SUCH AS ADVERSE DRUG REACTIONS, DEVELOPMENTAL ABNORMALITIES, AND CANCER. THEREFORE, RIGOROUS STUDIES ARE ESSENTIAL TO MINIMIZE THE RISKS ASSOCIATED WITH EPIGENETIC THERAPIES AND TO DEVELOP SAFE AND EFFECTIVE INTERVENTIONS FOR IMPROVING HUMAN HEALTH. THIS ARTICLE PROVIDES A SYNTHETIC AND HISTORICAL VIEW OF THE ORIGIN OF EPIGENETICS AND SOME OF THE MOST RELEVANT ACHIEVEMENTS. 2023 13 34 28 A CHILD'S NUTRITION AND EPIGENETICS. STUDIES HAVE SHOWN A DRAMATIC INCREASE IN THE INCIDENCE AND THE PREVALENCE OF CHRONIC DISEASES SUCH AS TYPE 2 DIABETES MELLITUS AND CARDIOVASCULAR DISORDERS OVER THE LAST SEVERAL DECADES. ENVIRONMENTAL TRIGGERS AND NUTRITION ARE CONSIDERED MAJOR CONTRIBUTORS TO THIS INCREASE. THE FIRST 1,000 DAYS OF LIFE, WHICH IS THE PERIOD BETWEEN CONCEPTION AND THE FIRST 2 YEARS OF AGE, IS CONSIDERED THE TIME FOR ENVIRONMENTAL FACTORS, SUCH AS NUTRITION, TO EXERT THEIR POSITIVE AND MOST CRUCIAL EFFECTS ON A CHILD'S HEALTH. NUTRIGENOMICS, THE STUDY OF HOW GENES AND FOOD COMPONENTS INTERACT, LOOKS INTO DIET-ALTERING DISEASE DEVELOPMENT BY MODULATING PROCESSES INVOLVED WITH THE ONSET, PROGRESSION, AND SEVERITY OF DISEASE. THESE FACTORS AFFECTING THE DEVELOPMENT OF THESE CHRONIC DISEASES ARE THOUGHT TO BE MEDIATED BY EPIGENETIC MECHANISMS, WHICH ARE HERITABLE AND REVERSIBLE, AND CARRY GENETIC INFORMATION WITHOUT CHANGING THE NUCLEOTIDE SEQUENCE OF THE GENOME AND ARE ALSO MEDIATED BY MATERNAL AND POSTNATAL NUTRITION. 2023 14 2562 27 EPIGENETICS IN THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE: INFLUENCE OF EXERCISE AND NUTRITION. INCREASING EVIDENCE LINKS CHANGES IN EPIGENETIC SYSTEMS, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA EXPRESSION, TO THE OCCURRENCE OF CARDIOVASCULAR DISEASE (CVD). THESE EPIGENETIC MODIFICATIONS CAN CHANGE GENETIC FUNCTION UNDER INFLUENCE OF EXOGENOUS STIMULI AND CAN BE TRANSFERRED TO NEXT GENERATIONS, PROVIDING A POTENTIAL MECHANISM FOR INHERITANCE OF BEHAVIOURAL INTERVENTION EFFECTS. THE BENEFITS OF EXERCISE AND NUTRITIONAL INTERVENTIONS IN THE PRIMARY AND SECONDARY PREVENTION OF CVD ARE WELL ESTABLISHED, BUT THE MECHANISMS ARE NOT COMPLETELY UNDERSTOOD. IN THIS REVIEW, WE DESCRIBE THE ACUTE AND CHRONIC EPIGENETIC EFFECTS OF PHYSICAL ACTIVITY AND DIETARY CHANGES. WE PROPOSE EXERCISE AND NUTRITION AS POTENTIAL TRIGGERS OF EPIGENETIC SIGNALS, PROMOTING THE RESHAPING OF TRANSCRIPTIONAL PROGRAMMES WITH EFFECTS ON CVD PHENOTYPES. FINALLY, WE HIGHLIGHT RECENT DEVELOPMENTS IN EPIGENETIC THERAPEUTICS WITH IMPLICATIONS FOR PRIMARY AND SECONDARY CVD PREVENTION. 2022 15 6251 36 THE MICROBIOLOGICAL MEMORY, AN EPIGENETIC REGULATOR GOVERNING THE BALANCE BETWEEN GOOD HEALTH AND METABOLIC DISORDERS. IF THE TRANSMISSION OF BIOLOGICAL INFORMATION FROM ONE GENERATION TO THE NEXT IS BASED ON DNA, MOST HERITABLE PHENOTYPIC TRAITS SUCH AS CHRONIC METABOLIC DISEASES, ARE NOT LINKED TO GENETIC VARIATION IN DNA SEQUENCES. NON-GENETIC HERITABILITY MIGHT HAVE SEVERAL CAUSES INCLUDING EPIGENETIC, PARENTAL EFFECT, ADAPTIVE SOCIAL LEARNING, AND INFLUENCE OF THE ECOLOGICAL ENVIRONMENT. DISTINGUISHING AMONG THESE CAUSES IS CRUCIAL TO RESOLVE MAJOR PHENOTYPIC ENIGMAS. STRONG EVIDENCE INDICATES THAT CHANGES IN DNA EXPRESSION THROUGH VARIOUS EPIGENETIC MECHANISMS CAN BE LINKED TO PARENT-OFFSPRING RESEMBLANCE IN TERMS OF SENSITIVITY TO METABOLIC DISEASES. AMONG NON-GENETIC HERITABLE TRAITS, EARLY NUTRITION COULD ACCOUNT FOR A LONG TERM DEVIANT PROGRAMMING OF GENES EXPRESSION RESPONSIBLE FOR METABOLIC DISEASES IN ADULTHOOD. NUTRITION COULD SHAPE AN INADEQUATE GUT MICROBIOTA (DYSBIOSIS), TRIGGERING EPIGENETIC DEREGULATION OF TRANSCRIPTION WHICH CAN BE OBSERVED IN CHRONIC METABOLIC DISEASES. WE REVIEW HEREIN THE EVIDENCE THAT DYSBIOSIS MIGHT BE A MAJOR CAUSE OF HERITABLE EPIGENETIC PATTERNS FOUND TO BE ASSOCIATED WITH METABOLIC DISEASES. BY TAKING INTO ACCOUNT THE RECENT ADVANCES ON THE GUT MICROBIOME, WE HAVE AGGREGATED TOGETHER DIFFERENT OBSERVATIONS SUPPORTING THE HYPOTHESIS THAT THE GUT MICROBIOTA COULD PROMOTE THE MOLECULAR CROSSTALK BETWEEN BACTERIA AND SURROUNDING HOST CELLS WHICH CONTROLS THE PATHOLOGICAL EPIGENETIC SIGNATURE. WE INTRODUCE FOR THE FIRST TIME THE CONCEPT OF "MICROBIOLOGICAL MEMORY" AS THE MAIN REGULATOR OF THE EPIGENETIC SIGNATURES, THEREBY INDICATING THAT DIFFERENT CAUSES OF NON-GENETIC HERITABILITY CAN INTERACT IN COMPLEX PATHWAYS TO PRODUCE INHERITANCE. 2018 16 4273 34 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 17 3593 37 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 18 1155 31 CONSIDERING MATERNAL DIETARY MODULATORS FOR EPIGENETIC REGULATION AND PROGRAMMING OF THE FETAL EPIGENOME. FETAL LIFE IS CHARACTERIZED BY A TREMENDOUS PLASTICITY AND ABILITY TO RESPOND TO VARIOUS ENVIRONMENTAL AND LIFESTYLE FACTORS, INCLUDING MATERNAL NUTRITION. IDENTIFICATION OF THE ROLE OF DIETARY FACTORS THAT CAN MODULATE AND RESHAPE THE CELLULAR EPIGENOME DURING DEVELOPMENT, INCLUDING METHYL GROUP DONORS (E.G., FOLATE, CHOLINE) AND BIOACTIVE COMPOUNDS (E.G., POLYPHENOLS) IS OF GREAT IMPORTANCE; HOWEVER, THERE IS INSUFFICIENT KNOWLEDGE OF A PARTICULAR EFFECT OF EACH TYPE OF MODULATOR AND/OR THEIR COMBINATION ON FETAL LIFE. TO ENHANCE THE QUALITY AND SAFETY OF FOOD PRODUCTS FOR PROPER FETAL HEALTH AND DISEASE PREVENTION IN LATER LIFE, A BETTER UNDERSTANDING OF THE UNDERLYING MECHANISMS OF DIETARY EPIGENETIC MODULATORS DURING THE CRITICAL PRENATAL PERIOD IS NECESSARY. THIS REVIEW FOCUSES ON THE INFLUENCE OF MATERNAL DIETARY COMPONENTS ON DNA METHYLATION, HISTONE MODIFICATION, AND MICRORNAS, AND SUMMARIZES CURRENT KNOWLEDGE OF THE EFFECT AND IMPORTANCE OF DIETARY COMPONENTS ON EPIGENETIC MECHANISMS THAT CONTROL THE PROPER EXPRESSION OF GENETIC INFORMATION. EVIDENCE REVEALS THAT SOME COMPONENTS IN THE MATERNAL DIET CAN DIRECTLY OR INDIRECTLY AFFECT EPIGENETIC MECHANISMS. UNDERSTANDING THE UNDERLYING MECHANISMS OF HOW EARLY-LIFE NUTRITIONAL ENVIRONMENT AFFECTS THE EPIGENOME DURING DEVELOPMENT IS OF GREAT IMPORTANCE FOR THE SUCCESSFUL PREVENTION OF ADULT CHRONIC DISEASES THROUGH OPTIMAL MATERNAL NUTRITION. 2015 19 2584 31 EPIGENETICS OF OBESITY. OBESITY IS A METABOLIC DISEASE, WHICH IS BECOMING AN EPIDEMIC HEALTH PROBLEM: IT HAS BEEN RECENTLY DEFINED IN TERMS OF GLOBAL PANDEMIC. OVER THE YEARS, THE APPROACHES THROUGH FAMILY, TWINS AND ADOPTION STUDIES LED TO THE IDENTIFICATION OF SOME CAUSAL GENES IN MONOGENIC FORMS OF OBESITY BUT THE ORIGINS OF THE PANDEMIC OF OBESITY CANNOT BE CONSIDERED ESSENTIALLY DUE TO GENETIC FACTORS, BECAUSE HUMAN GENOME IS NOT LIKELY TO CHANGE IN JUST A FEW YEARS. EPIGENETIC STUDIES HAVE OFFERED IN RECENT YEARS VALUABLE TOOLS FOR THE UNDERSTANDING OF THE WORLDWIDE SPREAD OF THE PANDEMIC OF OBESITY. THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS-DNA METHYLATION, HISTONE TAILS, AND MIRNAS MODIFICATIONS-IN THE DEVELOPMENT OF OBESITY IS MORE AND MORE EVIDENT. IN THE EPIGENETIC LITERATURE, THERE ARE EVIDENCES THAT THE ENTIRE EMBRYO-FETAL AND PERINATAL PERIOD OF DEVELOPMENT PLAYS A KEY ROLE IN THE PROGRAMMING OF ALL HUMAN ORGANS AND TISSUES. THEREFORE, THE MOLECULAR MECHANISMS INVOLVED IN THE EPIGENETIC PROGRAMMING REQUIRE A NEW AND GENERAL PATHOGENIC PARADIGM, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY, TO EXPLAIN THE CURRENT EPIDEMIOLOGICAL TRANSITION, THAT IS, THE WORLDWIDE INCREASE OF CHRONIC, DEGENERATIVE, AND INFLAMMATORY DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES, AND CANCER. OBESITY AND ITS RELATED COMPLICATIONS ARE MORE AND MORE ASSOCIATED WITH ENVIRONMENTAL POLLUTANTS (OBESOGENS), GUT MICROBIOTA MODIFICATIONS AND UNBALANCED FOOD INTAKE, WHICH CAN INDUCE, THROUGH EPIGENETIC MECHANISMS, WEIGHT GAIN, AND ALTERED METABOLIC CONSEQUENCES. 2016 20 3706 34 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING. 2007