1 2517 87 EPIGENETICS AND THE BURDEN OF NONCOMMUNICABLE DISEASE: A PAUCITY OF RESEARCH IN AFRICA. EPIDEMIOLOGICAL EVIDENCE SUGGESTS THAT AN ADVERSE IN UTERO ENVIRONMENT IS ASSOCIATED WITH AN INCREASED RISK FOR DEVELOPING ADULT ONSET DISEASES. THE MOLECULAR MECHANISMS FOR SUSCEPTIBILITY TO CHRONIC NONCOMMUNICABLE DISEASES ARE NOT FULLY UNDERSTOOD, ALTHOUGH RECENT RESEARCH HAS PROPOSED THAT EPIGENETIC MODIFICATIONS PLAY AN IMPORTANT ROLE IN FETAL PROGRAMMING. GENETIC AND ENVIRONMENTAL FACTORS CONTRIBUTE TO INTERINDIVIDUAL AND SPATIOTEMPORAL TISSUE-SPECIFIC METHYLATION PATTERNS. ALTHOUGH THE DIVERSE ENVIRONMENTS AND HIGH GENETIC DIVERSITY OF AFRICAN POPULATIONS PROVIDE UNPARALLELED POTENTIAL TO INVESTIGATE THE EFFECTS OF ENVIRONMENTAL CHANGE ON THE EPIGENETIC PROFILE IN HUMANS, ONLY A SMALL PERCENTAGE OF GENOMIC AND EPIGENETIC STUDIES HAVE FOCUSED ON POPULATIONS FROM THIS CONTINENT. THIS EMPHASIZES THE NEED TO BUILD CAPACITY IN AFRICA FOR RESEARCH THAT LEADS TO AN UNDERSTANDING OF THE ASSOCIATION BETWEEN GENETIC, EPIGENETIC AND ENVIRONMENTAL RISK FACTORS FOR NONCOMMUNICABLE DISEASES ON THE CONTINENT. 2015 2 1938 38 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 3 2103 28 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 4 2495 39 EPIGENETICS AND DOHAD: FROM BASICS TO BIRTH AND BEYOND. DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) IS THE STUDY OF HOW THE EARLY LIFE ENVIRONMENT CAN IMPACT THE RISK OF CHRONIC DISEASES FROM CHILDHOOD TO ADULTHOOD AND THE MECHANISMS INVOLVED. EPIGENETIC MODIFICATIONS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS ARE INVOLVED IN MEDIATING HOW EARLY LIFE ENVIRONMENT IMPACTS LATER HEALTH. THIS REVIEW IS A SUMMARY OF THE EPIGENETICS AND DOHAD WORKSHOP HELD AT THE 2016 DOHAD SOCIETY OF AUSTRALIA AND NEW ZEALAND CONFERENCE. OUR EXTENSIVE KNOWLEDGE OF HOW THE EARLY LIFE ENVIRONMENT IMPACTS LATER RISK FOR CHRONIC DISEASE WOULD NOT HAVE BEEN POSSIBLE WITHOUT ANIMAL MODELS. IN THIS REVIEW WE HIGHLIGHT SOME ANIMAL MODEL EXAMPLES THAT DEMONSTRATE HOW AN ADVERSE EARLY LIFE EXPOSURE RESULTS IN EPIGENETIC AND GENE EXPRESSION CHANGES THAT MAY CONTRIBUTE TO INCREASED RISK OF CHRONIC DISEASE LATER IN LIFE. TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE ARE CHRONIC DISEASES WITH AN INCREASING INCIDENCE DUE TO THE INCREASED NUMBER OF CHILDREN AND ADULTS THAT ARE OBESE. EPIGENETIC CHANGES SUCH AS DNA METHYLATION HAVE BEEN SHOWN TO BE ASSOCIATED WITH METABOLIC HEALTH MEASURES AND POTENTIALLY PREDICT FUTURE METABOLIC HEALTH STATUS. ALTHOUGH MORE DIFFICULT TO ELUCIDATE IN HUMANS, RECENT STUDIES SUGGEST THAT DNA METHYLATION MAY BE ONE OF THE EPIGENETIC MECHANISMS THAT MEDIATES THE EFFECTS OF EARLY LIFE EXPOSURES ON LATER LIFE RISK OF OBESITY AND OBESITY RELATED DISEASES. FINALLY, WE DISCUSS THE ROLE OF THE MICROBIOME AND HOW IT IS A NEW PLAYER IN DEVELOPMENTAL PROGRAMMING AND MEDIATING EARLY LIFE EXPOSURES ON LATER RISK OF CHRONIC DISEASE. 2017 5 2007 32 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 6 6823 29 [GENERAL CONCEPTS OF EPIGENETICS: PROJECTIONS IN PAEDIATRICS]. CURRENT EVIDENCE SUPPORTS THE NOTION THAT ALTERATIONS IN INTRAUTERINE GROWTH AND DURING THE FIRST YEARS OF LIFE HAVE A SUBSTANTIAL EFFECT ON THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASE, WHICH IN SOME CASES IS EVEN HIGHER THAN THOSE DUE TO GENETIC FACTORS. THE PERSISTENCE AND REPRODUCIBILITY OF THE PHENOTYPES ASSOCIATED WITH ALTERED EARLY DEVELOPMENT SUGGEST THE PARTICIPATION OF MECHANISMS THAT WOULD RECORD ENVIRONMENTAL CUES, GENERATING A CELLULAR REPROGRAMMING (I.E., EPIGENETIC MECHANISMS). THIS REVIEW IS AN INTRODUCTION TO A SERIES OF FIVE ARTICLES FOCUSED ON THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF HIGHLY PREVALENT CHRONIC DISEASES (I.E., CARDIOVASCULAR, METABOLIC, ASTHMA/ALLERGIES AND CANCER) AND THEIR ORIGINS IN THE FOETAL AND NEONATAL PERIOD. THIS SERIES OF ARTICLES AIMS TO SHOW THE STATE OF THE ART IN THIS RESEARCH AREA AND PRESENT THE UPCOMING CLUES AND CHALLENGES, IN WHICH PAEDIATRICIANS HAVE A PROMINENT ROLE, DEVELOPING STRATEGIES FOR THE PREVENTION, EARLY DETECTION AND FOLLOW-UP. 2016 7 2651 33 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 8 2496 31 EPIGENETICS AND EARLY LIFE ORIGINS OF CHRONIC NONCOMMUNICABLE DISEASES. IN LIGHT OF THE INCREASING THREATS OF CHRONIC NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES, THE GROWING RECOGNITION OF THE EARLY LIFE ORIGINS OF CHRONIC DISEASE, AND INNOVATIVE BREAKTHROUGHS IN BIOMEDICAL RESEARCH AND TECHNOLOGY, IT IS IMPERATIVE THAT WE HARNESS CUTTING-EDGE DATA TO IMPROVE HEALTH PROMOTION AND MAINTENANCE. IT IS WELL RECOGNIZED THAT CHRONIC DISEASES ARE COMPLEX TRAITS AFFECTED BY A WIDE RANGE OF ENVIRONMENTAL AND GENETIC FACTORS; HOWEVER, THE ROLE OF EPIGENETIC FACTORS, PARTICULARLY WITH REGARD TO EARLY LIFE ORIGINS, REMAINS LARGELY UNEXPLORED. GIVEN THE UNIQUE PROPERTIES OF THE EPIGENOME-FUNCTIONALITY DURING CRITICAL TIME WINDOWS, SUCH AS THE INTRAUTERINE PERIOD, HERITABILITY, AND REVERSIBILITY-ENHANCING OUR UNDERSTANDING OF EPIGENETIC MECHANISMS MAY OFFER NEW OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL EARLY PREDICTION AND PREVENTION PARADIGMS. THIS MAY PRESENT AN UNPARALLELED OPPORTUNITY TO OFFER MATERNAL AND CHILD HEALTH PROFESSIONALS IMPORTANT TOOLS WITH THE TRANSLATIONAL VALUE TO PREDICT, DETECT, AND PREVENT DISEASE AT AN EARLY AGE, LONG BEFORE ITS CLINICAL OCCURRENCE, AND AS SUCH, BREAK LIFELONG AND TRANSGENERATIONAL CYCLES OF DISEASE. IN DOING SO, MODERN TECHNOLOGY CAN BE LEVERAGED TO MAKE GREAT CONTRIBUTIONS TO POPULATION HEALTH, QUALITY OF LIFE, AND REDUCING THE BURDENSOME ECONOMIC COSTS OF NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES. 2013 9 2584 37 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 10 46 30 A CONCEPTUAL FRAMEWORK FOR THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. IN THE LAST DECADES, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HAVE EMERGED AS A VIGOROUS FIELD COMBINING EXPERIMENTAL, CLINICAL, EPIDEMIOLOGICAL AND PUBLIC HEALTH RESEARCH. ITS GOAL IS TO UNDERSTAND HOW EVENTS IN EARLY LIFE SHAPE LATER MORBIDITY RISK, ESPECIALLY OF NON-COMMUNICABLE CHRONIC DISEASES. AS THESE DISEASES BECOME THE MAJOR CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, RESEARCH ARISING FROM DOHAD IS LIKELY TO GAIN SIGNIFICANCE TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT. BUT ACTION MAY BE HINDERED BY THE LACK OF A FIRM MECHANISTIC EXPLANATION AND OF A CONCEPTUAL BASIS, ESPECIALLY REGARDING THE EVOLUTIONARY SIGNIFICANCE OF THE DOHAD PHENOMENON. IN THIS ARTICLE, WE PROVIDE A SUCCINCT HISTORICAL REVIEW OF THE RESEARCH INTO THE RELATIONSHIP BETWEEN DEVELOPMENT AND LATER DISEASE, CONSIDER THE EVOLUTIONARY AND DEVELOPMENTAL SIGNIFICANCE AND DISCUSS THE UNDERLYING MECHANISMS OF THE DOHAD PHENOMENON. DOHAD SHOULD BE VIEWED AS A PART OF A BROADER BIOLOGICAL MECHANISM OF PLASTICITY BY WHICH ORGANISMS, IN RESPONSE TO CUES SUCH AS NUTRITION OR HORMONES, ADAPT THEIR PHENOTYPE TO ENVIRONMENT. THESE RESPONSES MAY BE DIVIDED INTO THOSE FOR IMMEDIATE BENEFIT AND THOSE AIMED AT PREDICTION OF A FUTURE ENVIRONMENT: DISEASE OCCURS IN THE MISMATCH BETWEEN PREDICTED AND REALIZED FUTURE. THE LIKELY MECHANISMS THAT ENABLE PLASTICITY INVOLVE EPIGENETIC PROCESSES, AFFECTING THE EXPRESSION OF GENES ASSOCIATED WITH REGULATORY PATHWAYS. THERE IS NOW EVIDENCE THAT EPIGENETIC MARKS MAY BE INHERITED AND SO CONTRIBUTE TO NON-GENOMIC HERITABLE DISEASE RISK. WE END BY DISCUSSING THE GLOBAL SIGNIFICANCE OF THE DOHAD PHENOMENON AND ITS POTENTIAL APPLICATIONS FOR PUBLIC HEALTH PURPOSES. 2010 11 4802 36 OBESITY AND LIFESPAN HEALTH--IMPORTANCE OF THE FETAL ENVIRONMENT. A MARKED INCREASE IN THE FREQUENCY OF OBESITY AT THE POPULATION LEVEL HAS RESULTED IN AN INCREASING NUMBER OF OBESE WOMEN ENTERING PREGNANCY. THE INCREASING REALIZATION OF THE IMPORTANCE OF THE FETAL ENVIRONMENT IN RELATION TO CHRONIC DISEASE ACROSS THE LIFESPAN HAS FOCUSED ATTENTION ON THE ROLE OF MATERNAL OBESITY IN FETAL DEVELOPMENT. PREVIOUS STUDIES HAVE DEMONSTRATED THAT OBESITY DURING ADOLESCENCE AND ADULTHOOD CAN BE TRACED BACK TO FETAL AND EARLY CHILDHOOD EXPOSURES. THIS REVIEW FOCUSES ON FACTORS THAT CONTRIBUTE TO EARLY DEVELOPMENTAL EVENTS, SUCH AS EPIGENETIC MODIFICATIONS, THE POTENTIAL FOR AN INCREASE IN INFLAMMATORY BURDEN, EARLY DEVELOPMENTAL PROGRAMMING CHANGES SUCH AS THE VARIABLE DEVELOPMENT OF WHITE VERSUS BROWN ADIPOSE TISSUE, AND ALTERATIONS IN ORGAN ONTOGENY. WE HYPOTHESIZE THAT THESE MECHANISMS PROMOTE AN UNFAVORABLE FETAL ENVIRONMENT AND CAN HAVE A LONG-STANDING IMPACT, WITH EARLY MANIFESTATIONS OF CHRONIC DISEASE THAT CAN RESULT IN AN INCREASED DEMAND FOR FUTURE HEALTH CARE. IN ORDER TO IDENTIFY APPROPRIATE PREVENTIVE MEASURES, ATTENTION NEEDS TO BE PLACED BOTH ON REDUCING MATERNAL OBESITY AS WELL AS UNDERSTANDING THE MOLECULAR, CELLULAR, AND EPIGENETIC MECHANISMS THAT MAY BE RESPONSIBLE FOR THE PRENATAL ONSET OF CHRONIC DISEASE. 2014 12 1801 35 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 13 3771 34 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 6191 35 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 15 6892 25 [SIGNIFICANCE OF PREVENTING DEVELOPMENTAL ORIGINS OF DISEASES IN IMPROVING POPULATION QUALITY]. MORE STUDIES SHOW THAT VARIOUS DISEASES, ESPECIALLY CHRONIC NON-INFECTIOUS DISEASES, HAVE DEVELOPMENTAL ORIGIN. DEVELOPMENTAL ORIGINS OF DISEASES ARE MAINLY DUE TO GAMETES AND EARLY LIFE DEVELOPMENT STAGE BEING EXPOSED TO ADVERSE ENVIRONMENT, RESULTING IN ABNORMAL MODIFICATION OF EPIGENETIC AND STABLE INHERITANCE TO THE ADULT STAGE, WHICH COULD MAKE THE RISK OF VARIOUS LONG-TERM DISEASES OF INDIVIDUALS HIGH. THE THEORY OF DEVELOPMENTAL ORIGIN PROVIDES A NEW PERSPECTIVE FOR THE OCCURRENCE AND DEVELOPMENT OF DISEASES, AND ALSO PROVIDES A THEORETICAL BASIS FOR DISEASE PREVENTION. ATTACHING IMPORTANCE TO MATERNAL AND CHILD HEALTH CARE AND LIFE-CYCLE MANAGEMENT IS CONDUCIVE TO THE PREVENTION OF DEVELOPMENTAL DISEASES AND IS OF GREAT SIGNIFICANCE TO THE IMPROVEMENT OF POPULATION QUALITY. 2023 16 3580 33 IMPACT OF PERINATAL ENVIRONMENTAL TOBACCO SMOKE ON THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES. ALLERGIC DISEASES SUCH AS ASTHMA, ALLERGIC RHINITIS, ATOPIC DERMATITIS, AND FOOD ALLERGY, ARE MOST COMMON CHRONIC, NONCOMMUNICABLE DISEASES IN CHILDHOOD. IN THE PAST FEW DECADES, THE PREVALENCE HAS INCREASED ABRUPTLY WORLDWIDE. THERE ARE 2 POSSIBLE EXPLANATIONS FOR THE RISING PREVALENCE OF ALLERGIC DISEASES WORLDWIDE, THAT AN INCREASED DISEASE-AWARENESS OF PHYSICIAN, PATIENT, OR CAREGIVERS, AND AN ABRUPT EXPOSURE TO UNKNOWN HAZARDS. UNFORTUNATELY, THE UNDERLYING MECHANISMS REMAIN LARGELY UNKNOWN. DESPITE THE CONTINUING EFFORTS WORLDWIDE, THE ETIOLOGIES AND RISING PREVALENCE REMAIN UNCLEAR. THUS, IT IS IMPORTANT TO IDENTIFY AND CONTROL RISK FACTORS IN THE SUSCEPTIBLE INDIVIDUAL FOR THE BEST PREVENTION AND MANAGEMENT. GENETIC SUSCEPTIBILITY OR ENVIRONMENTS MAY BE A POTENTIAL BACKGROUND FOR THE DEVELOPMENT OF ALLERGIC DISEASE, HOWEVER THEY ALONE CANNOT EXPLAIN THE RISING PREVALENCE WORLDWIDE. THERE IS GROWING EVIDENCE THAT EPIGENETIC CHANGE DEPENDS ON THE GENE, ENVIRONMENT, AND THEIR INTERACTIONS, MAY INDUCE A LONG-LASTING ALTERED GENE EXPRESSION AND THE CONSEQUENT DEVELOPMENT OF ALLERGIC DISEASES. IN EPIGENETIC MECHANISMS, ENVIRONMENTAL TOBACCO SMOKE (ETS) EXPOSURE DURING CRITICAL PERIOD (I.E., DURING PREGNANCY AND EARLY LIFE) ARE CONSIDERED AS A POTENTIAL CAUSE OF THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES. HOWEVER, THE CAUSAL RELATIONSHIP IS STILL UNCLEAR. THIS REVIEW AIMED TO HIGHLIGHT THE IMPACT OF ETS EXPOSURE DURING THE PERINATAL PERIOD ON THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES AND TO PROPOSE A FUTURE RESEARCH DIRECTION. 2016 17 6844 28 [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 18 6630 30 UNDERSTANDING THE INTERPLAY BETWEEN HEALTH DISPARITIES AND EPIGENOMICS. SOCIAL EPIGENOMICS HAS EMERGED AS AN INTEGRATIVE FIELD OF RESEARCH FOCUSED ON IDENTIFICATION OF SOCIO-ENVIRONMENTAL FACTORS, THEIR INFLUENCE ON HUMAN BIOLOGY THROUGH EPIGENOMIC MODIFICATIONS, AND HOW THEY CONTRIBUTE TO CURRENT HEALTH DISPARITIES. SEVERAL HEALTH DISPARITIES STUDIES HAVE BEEN PUBLISHED USING GENETIC-BASED APPROACHES; HOWEVER, INCREASING ACCESSIBILITY AND AFFORDABILITY OF MOLECULAR TECHNOLOGIES HAVE ALLOWED FOR AN IN-DEPTH INVESTIGATION OF THE INFLUENCE OF EXTERNAL FACTORS ON EPIGENETIC MODIFICATIONS (E.G., DNA METHYLATION, MICRO-RNA EXPRESSION). CURRENTLY, RESEARCH IS FOCUSED ON EPIGENETIC CHANGES IN RESPONSE TO ENVIRONMENT, AS WELL AS TARGETED EPIGENETIC THERAPIES AND ENVIRONMENTAL/SOCIAL STRATEGIES FOR POTENTIALLY MINIMIZING CERTAIN HEALTH DISPARITIES. HERE, WE WILL REVIEW RECENT FINDINGS IN THIS FIELD PERTAINING TO CONDITIONS AND DISEASES OVER LIFE SPAN ENCOMPASSING PRENATAL TO ADULT STAGES. 2020 19 1932 32 ENVIRONMENTAL EXPOSURES: AN UNDERRECOGNIZED CONTRIBUTION TO NONCOMMUNICABLE DISEASES. PREVIOUS ATTEMPTS TO DETERMINE THE DEGREE TO WHICH EXPOSURE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO NONCOMMUNICABLE DISEASES (NCDS) HAVE BEEN VERY CONSERVATIVE AND HAVE SIGNIFICANTLY UNDERESTIMATED THE ACTUAL CONTRIBUTION OF THE ENVIRONMENT FOR AT LEAST TWO REASONS. FIRSTLY, MOST PREVIOUS REPORTS HAVE EXCLUDED THE CONTRIBUTION OF LIFESTYLE BEHAVIORAL RISK FACTORS, BUT THESE USUALLY INVOLVE SIGNIFICANT EXPOSURE TO ENVIRONMENTAL CHEMICALS THAT INCREASE RISK OF DISEASE. SECONDLY, EARLY LIFE EXPOSURE TO CHEMICAL CONTAMINANTS IS NOW CLEARLY ASSOCIATED WITH AN ELEVATED RISK OF SEVERAL DISEASES LATER IN LIFE, BUT THESE CONNECTIONS ARE OFTEN DIFFICULT TO DISCERN. THIS IS ESPECIALLY TRUE FOR ASTHMA AND NEURODEVELOPMENTAL CONDITIONS, BUT THERE IS ALSO A MAJOR CONTRIBUTION TO THE DEVELOPMENT OF OBESITY AND CHRONIC DISEASES. MOST CANCERS ARE CAUSED BY ENVIRONMENTAL EXPOSURES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. IN ADDITION, NEW INFORMATION SHOWS SIGNIFICANT ASSOCIATIONS BETWEEN CARDIOVASCULAR DISEASES AND DIABETES AND EXPOSURE TO ENVIRONMENTAL CHEMICALS PRESENT IN AIR, FOOD, AND WATER. THESE RELATIONSHIPS LIKELY REFLECT THE COMBINATION OF EPIGENETIC EFFECTS AND GENE INDUCTION. ENVIRONMENTAL FACTORS CONTRIBUTE SIGNIFICANTLY MORE TO NCDS THAN PREVIOUS REPORTS HAVE SUGGESTED. PREVENTION NEEDS TO SHIFT FOCUS FROM INDIVIDUAL RESPONSIBILITY TO SOCIETAL RESPONSIBILITY AND AN UNDERSTANDING THAT EFFECTIVE PREVENTION OF NCDS ULTIMATELY RELIES ON IMPROVED ENVIRONMENTAL MANAGEMENT TO REDUCE EXPOSURE TO MODIFIABLE RISKS. 2013 20 3404 35 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