1 6378 114 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 2 1155 41 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 3 6063 44 THE DEVELOPMENTAL ENVIRONMENT, EPIGENETIC BIOMARKERS AND LONG-TERM HEALTH. EVIDENCE FROM BOTH HUMAN AND ANIMAL STUDIES HAS SHOWN THAT THE PRENATAL AND EARLY POSTNATAL ENVIRONMENTS INFLUENCE SUSCEPTIBILITY TO CHRONIC DISEASE IN LATER LIFE AND SUGGESTS THAT EPIGENETIC PROCESSES ARE AN IMPORTANT MECHANISM BY WHICH THE ENVIRONMENT ALTERS LONG-TERM DISEASE RISK. EPIGENETIC PROCESSES, INCLUDING DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNAS, PLAY A CENTRAL ROLE IN REGULATING GENE EXPRESSION. THE EPIGENOME IS HIGHLY SENSITIVE TO ENVIRONMENTAL FACTORS IN EARLY LIFE, SUCH AS NUTRITION, STRESS, ENDOCRINE DISRUPTION AND POLLUTION, AND CHANGES IN THE EPIGENOME CAN INDUCE LONG-TERM CHANGES IN GENE EXPRESSION AND PHENOTYPE. IN THIS REVIEW WE FOCUS ON HOW THE EARLY LIFE NUTRITIONAL ENVIRONMENT CAN ALTER THE EPIGENOME LEADING TO AN ALTERED SUSCEPTIBILITY TO DISEASE IN LATER LIFE. 2015 4 2930 37 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 5 5069 34 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 6 6844 36 [METABOLIC PROGRAMMING: THEORETICAL CONCEPTS AND EXPERIMENTAL EVIDENCE]. IT IS KNOWN THAT THE POOR NUTRITION DURING A FETAL DEVELOPMENT MAY CONTRIBUTE TO AN INCREASED RISK OF CHRONIC DISEASES IN ADULTHOOD. IN A MODERN LITERATURE, THIS PHENOMENON IS CALLED <>. IT IS ASSUMED THAT THE QUALITATIVE OR QUANTITATIVE DEFICIENCY OF CERTAIN NUTRITIONAL COMPONENTS DURING AN EARLY DEVELOPMENT MAY LEAD TO THE ADAPTATIONS THAT CONTRIBUTE TO IMPROVED SURVIVAL DURING THE PRENATAL AND EARLY POSTNATAL PERIODS OF AN ONTOGENESIS. HOWEVER, THE CONSEQUENCE OF SUCH ADAPTIVE CHANGES MAY ALSO BE THE DEVELOPMENT OF VARIOUS PATHOLOGICAL PROCESSES AT THE LATER STAGES OF LIFE. RECENT STUDIES HAVE SHOWN THAT ONE OF THE MAJOR MECHANISMS INVOLVED IN THESE ADAPTATIONS IS THE EPIGENETIC REGULATION OF A GENE ACTIVITY. IN THIS REVIEW, THE EXPERIMENTAL EVIDENCE IS PROVIDED THAT PROCESSES ARISING FROM A QUANTITATIVELY OR QUALITATIVELY RESTRICTED DIET DURING THE EARLY STAGES OF DEVELOPMENT PLAY AN IMPORTANT ROLE IN THE FURTHER LIFE AND CAN GREATLY INFLUENCE RISK OF VARIOUS AGE-RELATED DISEASES AND LIFE SPAN. 2013 7 6191 49 THE IMPACT OF MILK AND ITS COMPONENTS ON EPIGENETIC PROGRAMMING OF IMMUNE FUNCTION IN EARLY LIFE AND BEYOND: IMPLICATIONS FOR ALLERGY AND ASTHMA. SPECIFIC AND ADEQUATE NUTRITION DURING PREGNANCY AND EARLY LIFE IS AN IMPORTANT FACTOR IN AVOIDING NON-COMMUNICABLE DISEASES SUCH AS OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, CANCERS, AND CHRONIC ALLERGIC DISEASES. ALTHOUGH EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES HAVE SHOWN THAT NUTRITION IS IMPORTANT AT ALL STAGES OF LIFE, IT IS ESPECIALLY IMPORTANT IN PRENATAL AND THE FIRST FEW YEARS OF LIFE. DURING THE LAST DECADE, THERE HAS BEEN A GROWING INTEREST IN THE POTENTIAL ROLE OF EPIGENETIC MECHANISMS IN THE INCREASING HEALTH PROBLEMS ASSOCIATED WITH ALLERGIC DISEASE. EPIGENETICS INVOLVES SEVERAL MECHANISMS INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND MICRORNAS WHICH CAN MODIFY THE EXPRESSION OF GENES. IN THIS STUDY, WE FOCUS ON THE EFFECTS OF MATERNAL NUTRITION DURING PREGNANCY, THE EFFECTS OF THE BIOACTIVE COMPONENTS IN HUMAN AND BOVINE MILK, AND THE ENVIRONMENTAL FACTORS THAT CAN AFFECT EARLY LIFE (I.E., FARMING, MILK PROCESSING, AND BACTERIAL EXPOSURE), AND WHICH CONTRIBUTE TO THE EPIGENETIC MECHANISMS UNDERLYING THE PERSISTENT PROGRAMMING OF IMMUNE FUNCTIONS AND ALLERGIC DISEASES. THIS KNOWLEDGE WILL HELP TO IMPROVE APPROACHES TO NUTRITION IN EARLY LIFE AND HELP PREVENT ALLERGIES IN THE FUTURE. 2020 8 2103 37 EPIGENETIC EPIDEMIOLOGY OF THE DEVELOPMENTAL ORIGINS HYPOTHESIS. EXTENSIVE HUMAN EPIDEMIOLOGIC AND ANIMAL MODEL DATA INDICATE THAT DURING CRITICAL PERIODS OF PRENATAL AND POSTNATAL MAMMALIAN DEVELOPMENT, NUTRITION AND OTHER ENVIRONMENTAL STIMULI INFLUENCE DEVELOPMENTAL PATHWAYS AND THEREBY INDUCE PERMANENT CHANGES IN METABOLISM AND CHRONIC DISEASE SUSCEPTIBILITY. THE BIOLOGIC MECHANISMS UNDERLYING THIS "DEVELOPMENTAL ORIGINS HYPOTHESIS" ARE POORLY UNDERSTOOD. THIS REVIEW FOCUSES ON THE LIKELY INVOLVEMENT OF EPIGENETIC MECHANISMS IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). WE DESCRIBE PERMANENT EFFECTS OF TRANSIENT ENVIRONMENTAL INFLUENCES ON THE DEVELOPMENTAL ESTABLISHMENT OF EPIGENETIC GENE REGULATION AND EVIDENCE LINKING EPIGENETIC DYSREGULATION WITH HUMAN DISEASE. WE PROPOSE A DEFINITION OF "EPIGENETIC EPIDEMIOLOGY" AND DELINEATE HOW THIS EMERGING FIELD PROVIDES A BASIS FROM WHICH TO EXPLORE THE ROLE OF EPIGENETIC MECHANISMS IN DOHAD. WE SUGGEST STRATEGIES FOR FUTURE HUMAN EPIDEMIOLOGIC STUDIES TO IDENTIFY CAUSAL ASSOCIATIONS BETWEEN EARLY EXPOSURES, LONG-TERM CHANGES IN EPIGENETIC REGULATION, AND DISEASE, WHICH MAY ULTIMATELY ENABLE SPECIFIC EARLY-LIFE INTERVENTIONS TO IMPROVE HUMAN HEALTH. 2007 9 2562 36 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 10 4126 46 MECHANISMS OF DISEASE: THE DEVELOPMENTAL ORIGINS OF DISEASE AND THE ROLE OF THE EPIGENOTYPE. THERE IS ACCUMULATING EVIDENCE THAT MANY CHRONIC DISEASES SUCH AS TYPE 2 DIABETES AND CORONARY HEART DISEASE MIGHT ORIGINATE DURING EARLY LIFE. THIS EVIDENCE GIVES RISE TO THE DEVELOPMENTAL ORIGINS OF DISEASE HYPOTHESIS, AND IS SUPPORTED BY EPIDEMIOLOGICAL DATA IN HUMANS AND EXPERIMENTAL ANIMAL MODELS. A PERTURBED ENVIRONMENT IN EARLY LIFE IS THOUGHT TO ELICIT A RANGE OF PHYSIOLOGICAL AND CELLULAR ADAPTIVE RESPONSES IN KEY ORGAN SYSTEMS. THESE ADAPTIVE CHANGES RESULT IN PERMANENT ALTERATIONS AND MIGHT LEAD TO PATHOLOGY IN LATER LIFE. AGING ORGANS AND CELLS SEEM THEREFORE TO RETAIN A 'MEMORY' OF THEIR FETAL HISTORY AND ADAPTIVE RESPONSES. THE MECHANISMS UNDERLYING THE DEVELOPMENTAL ORIGINS OF DISEASE REMAIN POORLY DEFINED. EPIGENETIC TAGGING OF GENES, SUCH AS DNA METHYLATION AND HISTONE MODIFICATION, CONTROLS THE FUNCTION OF THE GENOME AT DIFFERENT LEVELS AND MAINTAINS CELLULAR MEMORY AFTER MANY CELLULAR DIVISIONS; IMPORTANTLY, TAGGING CAN BE MODULATED BY THE ENVIRONMENT AND IS INVOLVED IN ONSET OF DISEASES SUCH AS CANCER. HERE WE REVIEW THE EVIDENCE FOR THE DEVELOPMENTAL ORIGINS OF DISEASE AND DISCUSS THE ROLE OF THE EPIGENOTYPE AS A CONTRIBUTING MECHANISM. ENVIRONMENTALLY INDUCED CHANGES IN THE EPIGENOTYPE MIGHT BE KEY PRIMARY EVENTS IN THE DEVELOPMENTAL ORIGINS OF DISEASE, WITH IMPORTANT CLINICAL IMPLICATIONS. 2007 11 1801 46 EFFECT OF MATERNAL DIET ON THE EPIGENOME: IMPLICATIONS FOR HUMAN METABOLIC DISEASE. THE RAPID INCREASE IN THE INCIDENCE OF CHRONIC NON-COMMUNICABLE DISEASES OVER THE PAST TWO DECADES CANNOT BE EXPLAINED SOLELY BY GENETIC AND ADULT LIFESTYLE FACTORS. THERE IS NOW CONSIDERABLE EVIDENCE THAT THE FETAL AND EARLY POSTNATAL ENVIRONMENT ALSO STRONGLY INFLUENCES THE RISK OF DEVELOPING SUCH DISEASES IN LATER LIFE. HUMAN STUDIES HAVE SHOWN THAT LOW BIRTH WEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CVD, TYPE II DIABETES, OBESITY AND HYPERTENSION, ALTHOUGH RECENT STUDIES HAVE SHOWN THAT OVER-NUTRITION IN EARLY LIFE CAN ALSO INCREASE SUSCEPTIBILITY TO FUTURE METABOLIC DISEASE. THESE FINDINGS HAVE BEEN REPLICATED IN A VARIETY OF ANIMAL MODELS, WHICH HAVE SHOWN THAT BOTH MATERNAL UNDER- AND OVER-NUTRITION CAN INDUCE PERSISTENT CHANGES IN GENE EXPRESSION AND METABOLISM WITHIN THE OFFSPRING. THE MECHANISM BY WHICH THE MATERNAL NUTRITIONAL ENVIRONMENT INDUCES SUCH CHANGES IS BEGINNING TO BE UNDERSTOOD AND INVOLVES THE ALTERED EPIGENETIC REGULATION OF SPECIFIC GENES. THE DEMONSTRATION OF A ROLE FOR ALTERED EPIGENETIC REGULATION OF GENES IN THE DEVELOPMENTAL INDUCTION OF CHRONIC DISEASES RAISES THE POSSIBILITY THAT NUTRITIONAL OR PHARMACEUTICAL INTERVENTIONS MAY BE USED TO MODIFY LONG-TERM CARDIO-METABOLIC DISEASE RISK AND COMBAT THIS RAPID RISE IN CHRONIC NON-COMMUNICABLE DISEASES. 2011 12 2584 45 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 13 3771 46 INTER- AND TRANSGENERATIONAL EPIGENETIC INHERITANCE: EVIDENCE IN ASTHMA AND COPD? EVIDENCE IS NOW EMERGING THAT EARLY LIFE ENVIRONMENT CAN HAVE LIFELONG EFFECTS ON METABOLIC, CARDIOVASCULAR, AND PULMONARY FUNCTION IN OFFSPRING, A CONCEPT ALSO KNOWN AS FETAL OR DEVELOPMENTAL PROGRAMMING. IN MAMMALS, DEVELOPMENTAL PROGRAMMING IS THOUGHT TO OCCUR MAINLY VIA EPIGENETIC MECHANISMS, WHICH INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND EXPRESSION OF NON-CODING RNAS. THE EFFECTS OF DEVELOPMENTAL PROGRAMMING CAN BE INDUCED BY THE INTRAUTERINE ENVIRONMENT, LEADING TO INTERGENERATIONAL EPIGENETIC EFFECTS FROM ONE GENERATION TO THE NEXT. TRANSGENERATIONAL EPIGENETIC INHERITANCE MAY BE CONSIDERED WHEN DEVELOPMENTAL PROGRAMMING IS TRANSMITTED ACROSS GENERATIONS THAT WERE NOT EXPOSED TO THE INITIAL ENVIRONMENT WHICH TRIGGERED THE CHANGE. SO FAR, INTER- AND TRANSGENERATIONAL PROGRAMMING HAS BEEN MAINLY DESCRIBED FOR CARDIOVASCULAR AND METABOLIC DISEASE RISK. IN THIS REVIEW, WE DISCUSS AVAILABLE EVIDENCE THAT EPIGENETIC INHERITANCE ALSO OCCURS IN RESPIRATORY DISEASES, USING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AS EXAMPLES. WHILE MULTIPLE EPIDEMIOLOGICAL AS WELL AS ANIMAL STUDIES DEMONSTRATE EFFECTS OF 'TOXIC' INTRAUTERINE EXPOSURE ON VARIOUS ASTHMA-RELATED PHENOTYPES IN THE OFFSPRING, ONLY FEW STUDIES LINK EPIGENETIC MARKS TO THE OBSERVED PHENOTYPES. AS EPIGENETIC MARKS MAY DISTINGUISH INDIVIDUALS MOST AT RISK OF LATER DISEASE AT EARLY AGE, IT WILL ENABLE EARLY INTERVENTION STRATEGIES TO REDUCE SUCH RISKS. TO ACHIEVE THIS GOAL FURTHER, WELL DESIGNED EXPERIMENTAL AND HUMAN STUDIES ARE NEEDED. 2015 14 4794 31 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 15 6251 38 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 2226 52 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 17 2007 28 EPIGENETIC BASIS FOR FETAL ORIGINS OF AGE-RELATED DISEASE. THE CURRENT CONCEPT OF FETAL ORIGINS OF ADULT DISEASES DESCRIBES IN UTERO PROGRAMMING, OR ADAPTATION TO A SPECTRUM OF ADVERSE ENVIRONMENTAL CONDITIONS THAT ULTIMATELY LEADS TO INCREASED SUSCEPTIBILITY TO AGE-RELATED DISEASES (E.G., TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE) LATER IN LIFE. ALTHOUGH THE PRECISE MECHANISM OF THIS BIOLOGICAL MEMORY REMAINS UNCLEAR, MOUNTING EVIDENCE SUGGESTS AN EPIGENETIC BASIS. THE INCREASED SUSCEPTIBILITY TO CHRONIC DISEASE AND INVOLVEMENT OF MULTIPLE ORGAN SYSTEMS THAT IS OBSERVED IS ANALOGOUS TO THE DECLINE IN RESISTANCE TO DISEASE THAT IS TYPICAL OF NORMAL AGING. ALTHOUGH THE CUMULATIVE ENVIRONMENT OVER THE COURSE OF A LIFETIME CAN INDUCE INCREASING EPIGENETIC DYSREGULATION, WE PROPOSE THAT ADVERSE EVENTS THAT OCCUR DURING EARLY DEVELOPMENT CAN INDUCE SIGNIFICANT ADDITIONAL DYSREGULATION OF THE EPIGENOME. HERE, WE DESCRIBE THE CURRENT EVIDENCE FOR FETAL ORIGINS OF ADULT DISEASE AND THE ASSOCIATED ROLE OF EPIGENETIC DYSREGULATION. IN ADDITION, WE PRESENT A NEW PERSPECTIVE ON THE INDUCTION OF EPIGENETIC ALTERATIONS IN UTERO, WHICH SUBSEQUENTLY LEAD TO AN AGING PHENOTYPE MARKED BY INCREASED SUSCEPTIBILITY TO AGE-RELATED DISEASES. 2010 18 1938 43 EPIDEMIOLOGIC EVIDENCE FOR ASSOCIATION BETWEEN ADVERSE ENVIRONMENTAL EXPOSURES IN EARLY LIFE AND EPIGENETIC VARIATION: A POTENTIAL LINK TO DISEASE SUSCEPTIBILITY? A GROWING BODY OF EVIDENCE SUGGESTS THAT THE RISK OF DEVELOPMENT AND PROGRESSION OF A VARIETY OF HUMAN CHRONIC DISEASES DEPENDS ON EPIGENETIC MODIFICATIONS TRIGGERED BY ENVIRONMENTAL CUES DURING EARLY LIFE SENSITIVE STAGES. EXPOSURES TO ENVIRONMENTAL FACTORS SUCH AS ADVERSE NUTRITIONAL, PSYCHOLOGICAL, AND SOCIAL CONDITIONS, AS WELL AS POLLUTANTS AND SUBSTANCE ABUSE IN EARLY LIFE, HAVE BEEN SHOWN TO BE IMPORTANT DETERMINANTS OF EPIGENETIC PROGRAMMING OF CHRONIC PATHOLOGICAL CONDITIONS IN HUMAN POPULATIONS. OVER THE PAST YEARS, IT HAS BECOME INCREASINGLY CLEAR DUE TO THE EPIGENOME-WIDE ASSOCIATION STUDIES (EWASS) THAT EARLY LIFE ADVERSE ENVIRONMENTAL EVENTS MAY TRIGGER WIDESPREAD AND PERSISTENT ALTERATIONS IN TRANSCRIPTIONAL PROFILING. SEVERAL CANDIDATE GENES HAVE BEEN IDENTIFIED UNDERLYING THESE ASSOCIATIONS. IN THIS CONTEXT, DNA METHYLATION IS THE MOST INTENSIVELY STUDIED EPIGENETIC PHENOMENON. IN THIS REVIEW, THE CLINICAL AND EPIDEMIOLOGICAL EVIDENCE FOR THE ROLE OF EPIGENETIC FACTORS IN MEDIATING THE LINK BETWEEN EARLY LIFE EXPERIENCES AND LONG-TERM HEALTH OUTCOMES ARE SUMMARIZED. 2015 19 4460 39 MOLECULAR MECHANISMS OF ENVIRONMENTAL EXPOSURES AND HUMAN DISEASE. A SUBSTANTIAL PROPORTION OF DISEASE RISK FOR COMMON COMPLEX DISORDERS IS ATTRIBUTABLE TO ENVIRONMENTAL EXPOSURES AND POLLUTANTS. AN APPRECIATION OF HOW ENVIRONMENTAL POLLUTANTS ACT ON OUR CELLS TO PRODUCE DELETERIOUS HEALTH EFFECTS HAS LED TO ADVANCES IN OUR UNDERSTANDING OF THE MOLECULAR MECHANISMS UNDERLYING THE PATHOGENESIS OF CHRONIC DISEASES, INCLUDING CANCER AND CARDIOVASCULAR, NEURODEGENERATIVE AND RESPIRATORY DISEASES. HERE, WE DISCUSS EMERGING RESEARCH ON THE INTERPLAY OF ENVIRONMENTAL POLLUTANTS WITH THE HUMAN GENOME AND EPIGENOME. WE REVIEW EVIDENCE SHOWING THE ENVIRONMENTAL IMPACT ON GENE EXPRESSION THROUGH EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNAS. WE ALSO HIGHLIGHT RECENT STUDIES THAT EVALUATE RECENTLY DISCOVERED MOLECULAR PROCESSES THROUGH WHICH THE ENVIRONMENT CAN EXERT ITS EFFECTS, INCLUDING EXTRACELLULAR VESICLES, THE EPITRANSCRIPTOME AND THE MITOCHONDRIAL GENOME. FINALLY, WE DISCUSS CURRENT CHALLENGES WHEN STUDYING THE EXPOSOME - THE CUMULATIVE MEASURE OF ENVIRONMENTAL INFLUENCES OVER THE LIFESPAN - AND ITS INTEGRATION INTO FUTURE ENVIRONMENTAL HEALTH RESEARCH. 2023 20 4125 35 MECHANISMS OF DISEASE: IN UTERO PROGRAMMING IN THE PATHOGENESIS OF HYPERTENSION. NUTRITIONAL AND OTHER ENVIRONMENTAL CUES DURING DEVELOPMENT CAN PERMANENTLY ALTER THE STRUCTURE, HOMEOSTATIC SYSTEMS, AND FUNCTIONS OF THE BODY. THIS PHENOMENON HAS BEEN REFERRED TO AS 'PROGRAMMING'. EPIDEMIOLOGICAL AND ANIMAL STUDIES SHOW THAT PROGRAMMED EFFECTS OPERATE WITHIN THE NORMAL RANGE OF GROWTH AND DEVELOPMENT, AND INFLUENCE THE RISK OF CHRONIC DISEASE IN ADULT LIFE. WE REVIEW THE EVIDENCE THAT THESE EFFECTS INCLUDE REDUCED NEPHRON NUMBER AND COMPENSATORY ADAPTATIONS, WHICH MIGHT LEAD TO HYPERTENSION, AND PERHAPS ACCELERATE THE DECLINE IN RENAL FUNCTION THAT ACCOMPANIES AGING. THESE PROCESSES MIGHT BE EXACERBATED BY PROGRAMMED CHANGES IN VASCULAR STRUCTURE AND FUNCTION, AND ALTERATIONS IN ENDOCRINE AND METABOLIC HOMEOSTASIS. PROGRAMMED EFFECTS MIGHT BE INITIATED AS EARLY AS THE PERICONCEPTUAL PHASE OF DEVELOPMENT, AND COULD INVOLVE EPIGENETIC CHANGES IN GENE EXPRESSION OR ALTERED STEM CELL ALLOCATION. BETTER UNDERSTANDING OF THESE PROCESSES COULD LEAD TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND PREVENTIVE MEASURES, AND TO EARLY DETECTION OF AT-RISK INDIVIDUALS. BY MONITORING BLOOD PRESSURE, WEIGHT, AND RENAL FUNCTION IN CHILDREN, IT MIGHT BE POSSIBLE TO REDUCE THE RISK OF CARDIOVASCULAR AND RENAL DISEASE IN LATER LIFE. 2006