1 6454 144 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 2 5586 47 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 3 1865 49 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/. 2018 4 2136 39 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019 5 3919 49 LINKING DIET TO COLORECTAL CANCER: THE EMERGING ROLE OF MICRORNA IN THE COMMUNICATION BETWEEN PLANT AND ANIMAL KINGDOMS. ENVIRONMENTAL AND LIFESTYLE FACTORS, INCLUDING DIET AND NUTRITIONAL HABITS HAVE BEEN STRONGLY LINKED TO COLORECTAL CANCER (CRC). OF NOTE, UNHEALTHY DIETARY HABITS LEADING TO ADIPOSITY REPRESENT A MAIN RISK FACTOR FOR CRC AND ARE ASSOCIATED WITH A CHRONIC LOW-GRADE INFLAMMATORY STATUS. INFLAMMATION IS A HALLMARK OF ALMOST EVERY TYPE OF CANCER AND CAN BE MODULATED BY SEVERAL FOOD COMPOUNDS EXHIBITING EITHER PROTECTIVE OR PROMOTING EFFECTS. HOWEVER, IN SPITE OF AN EXTENSIVE RESEARCH, THE UNDERLYING MECHANISMS BY WHICH DIETARY PATTERNS OR BIOACTIVE FOOD COMPONENTS MAY INFLUENCE TUMOR ONSET AND OUTCOME HAVE NOT BEEN FULLY CLARIFIED YET. GROWING EVIDENCE INDICATES THAT DIET, COMBINING BENEFICIAL SUBSTANCES AND POTENTIALLY HARMFUL INGREDIENTS, HAS AN IMPACT ON THE EXPRESSION OF KEY REGULATORS OF GENE EXPRESSION SUCH AS THE NON-CODING RNA (NCRNA). SINCE THE EXPRESSION OF THESE MOLECULES IS DERANGED IN CHRONIC INFLAMMATION AND CANCER, MODULATING THEIR EXPRESSION MAY STRONGLY INFLUENCE THE CANCER PHENOTYPE AND OUTCOMES. IN ADDITION, THE RECENTLY ACQUIRED KNOWLEDGE ON THE EXISTENCE OF INTRICATE INTER-KINGDOM COMMUNICATION NETWORKS, IS OPENING NEW AVENUES FOR A DEEPER UNDERSTANDING OF THE INTIMATE RELATIONSHIPS LINKING DIET TO CRC. IN THIS NOVEL SCENARIO, DIET-MODULATED NCRNA MAY REPRESENT KEY ACTORS IN THE INTERACTION BETWEEN PLANT AND ANIMAL KINGDOMS, CAPABLE OF INFLUENCING DISEASE ONSET AND OUTCOME. IN THIS REVIEW, WE WILL SUMMARIZE THE STUDIES DEMONSTRATING A LINK BETWEEN BIOACTIVE FOOD COMPONENTS, INCLUDING FOOD-DERIVED, MICROBIOTA-PROCESSED, SECONDARY METABOLITES, AND HOST NCRNA. WE WILL FOCUS ON MICRORNA, HIGHLIGHTING HOW THIS PLANT/ANIMAL INTER-KINGDOM CROSS-TALK MAY HAVE AN IMPACT ON CRC ESTABLISHMENT AND PROGRESSION. 2017 6 2049 25 EPIGENETIC CODE AND POTENTIAL EPIGENETIC-BASED THERAPIES AGAINST CHRONIC DISEASES IN DEVELOPMENTAL ORIGINS. ACCUMULATED FINDINGS HAVE DEMONSTRATED THAT THE EPIGENETIC CODE PROVIDES A POTENTIAL LINK BETWEEN PRENATAL STRESS AND CHANGES IN GENE EXPRESSION THAT COULD BE INVOLVED IN THE DEVELOPMENTAL PROGRAMMING OF VARIOUS CHRONIC DISEASES IN LATER LIFE. MEANWHILE, BASED ON THE FACT THAT EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND CAN BE MANIPULATED, THIS PROVIDES A UNIQUE CHANCE TO DEVELOP MULTIPLE NOVEL EPIGENETIC-BASED THERAPEUTIC STRATEGIES AGAINST MANY CHRONIC DISEASES IN EARLY DEVELOPMENTAL PERIODS. THIS ARTICLE WILL GIVE A SHORT REVIEW OF RECENT FINDINGS OF PRENATAL INSULT-INDUCED EPIGENETIC CHANGES IN DEVELOPMENTAL ORIGINS OF SEVERAL CHRONIC DISEASES, AND WILL ATTEMPT TO PROVIDE AN OVERVIEW OF THE CURRENT EPIGENETIC-BASED STRATEGIES APPLIED IN THE EARLY PREVENTION, DIAGNOSIS AND POSSIBLE THERAPIES FOR HUMAN CHRONIC DISEASES. 2014 7 2586 26 EPIGENETICS OF PAIN MEDIATORS. PURPOSE OF REVIEW: THE FIELD OF EPIGENETICS CONTINUES ITS INFLUENTIAL RISE AS A MEANS TO BETTER UNDERSTAND AN ORGANISM'S UNIQUE DEVELOPMENTAL IDENTITY OVER A LIFESPAN. WHEREAS A GENOME IS CONSTANT AND UNCHANGING, AN EPIGENOME IS DYNAMIC AND ALTERABLE. EPIGENETIC CHANGES ARE IN RESPONSE TO INNUMERABLE INTERNAL AND EXTERNAL INFLUENCES INCLUDING ENVIRONMENTAL CHANGES SUCH AS DIET, EXERCISE, DISEASE, TOXINS, AND STRESS. EPIGENETICS IS OF PARTICULAR INTEREST IN THE MEDICAL RESEARCH COMMUNITY BOTH FOR THE POTENTIAL TO CAUSE DISEASE AND AS A TARGET FOR THERAPEUTIC INTERVENTIONS. THIS ARTICLE PROVIDES A SUCCINCT EXPLANATION OF THE POTENTIAL FOR EPIGENETICS TO INFLUENCE THE UNDERSTANDING OF PAIN AS WELL AS A REVIEW OF RELEVANT RESEARCH ON THE TOPIC. RECENT FINDINGS: STUDIES ON EPIGENETICS AND PAIN REMAIN LARGELY PRECLINICAL AND INVESTIGATE THE THEORETICAL ABILITY OF EPIGENETICS TO ALTER THE NOCICEPTIVE PATHWAYS BOTH IN THE PERIPHERY AND CENTRALLY. SIGNIFICANT EVIDENCE NOW EXISTS FOR THE ABILITY OF EPIGENETICS TO MODIFY BROADLY CATEGORIZED PAIN TYPES, INCLUDING INFLAMMATORY, NEUROPATHIC, VISCERAL, AND CANCER RELATED. SUMMARY: BOTH PATIENTS AND PROVIDERS RECOGNIZE THAT NOVEL MEDICATIONS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC PAIN CONDITIONS ARE SORELY NEEDED. THE UNDERSTANDING OF EPIGENETICS AND ITS INFLUENCE ON NOCICEPTION REMAINS IN RELATIVE INFANCY BUT EARLY EVIDENCE IS STRONG FOR POTENTIAL THERAPEUTIC BENEFITS TO TREAT THESE CONDITIONS. 2018 8 6858 31 [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 9 49 34 A CURRENT GENETIC AND EPIGENETIC VIEW ON HUMAN AGING MECHANISMS. THE PROCESS OF AGING IS ONE OF THE MOST COMPLEX AND INTRIGUING BIOLOGICAL PHENOMENONS. AGING IS A GENETICALLY REGULATED PROCESS IN WHICH THE ORGANISM'S MAXIMUM LIFESPAN POTENTIAL IS PRE-DETERMINED, WHILE THE RATE OF AGING IS INFLUENCED BY ENVIRONMENTAL FACTORS AND LIFESTYLE. CONSIDERING THE COMPLEXITY OF MECHANISMS INVOLVED IN THE REGULATION OF AGING PROCESS, UP TO THIS DATE THERE ISN'T A MAJOR, UNIFYING THEORY WHICH COULD EXPLAIN THEM. AS GENETIC/EPIGENETIC AND ENVIRONMENTAL FACTORS BOTH INEVITABLY INFLUENCE THE AGING PROCESS, HERE WE PRESENT A REVIEW ON THE GENETIC AND EPIGENETIC REGULATION OF THE MOST IMPORTANT MOLECULAR AND CELLULAR MECHANISMS INVOLVED IN THE PROCESS OF AGING. BASED ON THE STUDIES ON OXIDATIVE STRESS, METABOLISM, GENOME STABILITY, EPIGENETIC MODIFICATIONS AND CELLULAR SENESCENCE IN ANIMAL MODELS AND HUMANS, WE GIVE AN OVERVIEW OF KEY GENETIC AND MOLECULAR PATHWAYS RELATED TO AGING. AS MOST OF GENETIC MANIPULATIONS WHICH INFLUENCE THE AGING PROCESS ALSO AFFECT REPRODUCTION, WE DISCUSS AGING IN HUMANS AS A POST-REPRODUCTIVE GENETICALLY DETERMINED PROCESS. AFTER THE AGE OF REPRODUCTIVE SUCCESS, AGING CONTINOUSLY PROGRESSES WHICH CLINICALLY COINCIDES WITH THE ONSET OF MOST CHRONIC DISEASES, CANCERS AND DEMENTIONS. AS EVOLUTION SHAPES THE GENOMES FOR REPRODUCTIVE SUCCESS AND NOT FOR POST-REPRODUCTIVE SURVIVAL, AGING COULD BE DEFINED AS A PROTECTIVE MECHANISM WHICH ENSURES THE PRESERVATION AND PROGRESS OF SPECIES THROUGH THE MODIFICATION, TRASMISSION AND IMPROVEMENT OF GENETIC MATERIAL. 2009 10 2930 42 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 11 1405 46 DIETARY FACTORS AND EPIGENETIC REGULATION FOR PROSTATE CANCER PREVENTION. THE ROLE OF EPIGENETIC ALTERATIONS IN VARIOUS HUMAN CHRONIC DISEASES HAS GAINED INCREASING ATTENTION AND HAS RESULTED IN A PARADIGM SHIFT IN OUR UNDERSTANDING OF DISEASE SUSCEPTIBILITY. IN THE FIELD OF CANCER RESEARCH, E.G., GENETIC ABNORMALITIES/MUTATIONS HISTORICALLY WERE VIEWED AS PRIMARY UNDERLYING CAUSES; HOWEVER, EPIGENETIC MECHANISMS THAT ALTER GENE EXPRESSION WITHOUT AFFECTING DNA SEQUENCE ARE NOW RECOGNIZED AS BEING OF EQUAL OR GREATER IMPORTANCE FOR ONCOGENESIS. METHYLATION OF DNA, MODIFICATION OF HISTONES, AND INTERFERING MICRORNA (MIRNA) COLLECTIVELY REPRESENT A CADRE OF EPIGENETIC ELEMENTS DYSREGULATED IN CANCER. TARGETING THE EPIGENOME WITH COMPOUNDS THAT MODULATE DNA METHYLATION, HISTONE MARKS, AND MIRNA PROFILES REPRESENTS AN EVOLVING STRATEGY FOR CANCER CHEMOPREVENTION, AND THESE APPROACHES ARE STARTING TO SHOW PROMISE IN HUMAN CLINICAL TRIALS. ESSENTIAL MICRONUTRIENTS SUCH AS FOLATE, VITAMIN B-12, SELENIUM, AND ZINC AS WELL AS THE DIETARY PHYTOCHEMICALS SULFORAPHANE, TEA POLYPHENOLS, CURCUMIN, AND ALLYL SULFUR COMPOUNDS ARE AMONG A GROWING LIST OF AGENTS THAT AFFECT EPIGENETIC EVENTS AS NOVEL MECHANISMS OF CHEMOPREVENTION. TO ILLUSTRATE THESE CONCEPTS, THE CURRENT REVIEW HIGHLIGHTS THE INTERACTIONS AMONG NUTRIENTS, EPIGENETICS, AND PROSTATE CANCER SUSCEPTIBILITY. IN PARTICULAR, WE FOCUS ON EPIGENETIC DYSREGULATION AND THE IMPACT OF SPECIFIC NUTRIENTS AND FOOD COMPONENTS ON DNA METHYLATION AND HISTONE MODIFICATIONS THAT CAN ALTER GENE EXPRESSION AND INFLUENCE PROSTATE CANCER PROGRESSION. 2011 12 1453 27 DISCOVERING HOW ENVIRONMENTAL EXPOSURES ALTER GENES COULD LEAD TO NEW TREATMENTS FOR CHRONIC ILLNESSES. EMERGING RESEARCH DEMONSTRATES THAT DIET, POLLUTION, AND OTHER ENVIRONMENTAL TRIGGERS CAN ALTER BOTH THE FUNCTION AND EXPRESSION OF HUMAN GENES AND LEAD TO A HEIGHTENED DISEASE RISK. THESE ENVIRONMENT-GENE INTERACTIONS CAN CAUSE SO-CALLED EPIGENETIC CHANGES IN GENE EXPRESSION-PATTERNS OF WHICH GENES ARE SWITCHED "ON" OR "OFF"-THAT MAY ACCOUNT FOR THE RISING MORTALITY FROM CHRONIC DISEASES IN INDUSTRIALIZED NATIONS. IN THIS PAPER, WE CALL FOR A NEW TRANSDISCIPLINARY APPROACH TO PUBLIC HEALTH THAT WOULD EXAMINE HOW ENVIRONMENTAL EXPOSURES, BOTH PHYSICAL AND SOCIAL, INFLUENCE GENE EXPRESSION AND A PERSON'S SUSCEPTIBILITY TO CHRONIC DISEASE. THIS INITIATIVE COULD LEAD TO NEW WAYS TO PREVENT AND TREAT SUCH ILLNESSES. 2011 13 34 33 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 6204 43 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 15 2560 48 EPIGENETICS IN THE DEVELOPMENT, MODIFICATION, AND PREVENTION OF CARDIOVASCULAR DISEASE. EPIGENETICS HAS MAJOR RELEVANCE TO ALL DISEASE PROCESSES; CARDIOVASCULAR (CV) DISEASE AND ITS RELATED CONDITIONS ARE NO EXCEPTION. EPIGENETICS IS DEFINED AS THE STUDY OF HERITABLE ALTERATIONS IN GENE EXPRESSION, OR CELLULAR PHENOTYPE, AND GOES FAR BEYOND A PURE GENETIC APPROACH. A MORE PRECISE DEFINITION IS THAT EPIGENETICS REPRESENTS ALL THE MEIOTICALLY AND MITOTICALLY INHERITED CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED ON THE DEOXYRIBONUCLEIC ACID (DNA) SEQUENCE ITSELF. MAJOR EPIGENETIC MECHANISMS ARE MODIFICATIONS OF HISTONE PROTEINS IN CHROMATIN AND DNA METHYLATION (WHICH DOES NOT ALTER THE DNA SEQUENCE). THERE IS INCREASING EVIDENCE FOR THE INVOLVEMENT OF EPIGENETICS IN HUMAN DISEASE SUCH AS CANCER, INFLAMMATORY DISEASE AND CV DISEASE. OTHER CHRONIC DISEASES ARE ALSO SUSCEPTIBLE TO EPIGENETIC MODIFICATION SUCH AS METABOLIC DISEASES INCLUDING OBESITY, METABOLIC SYNDROME, AND DIABETES MELLITUS. THERE IS MUCH EVIDENCE FOR THE MODIFICATION OF EPIGENETICS BY NUTRITION AND EXERCISE. THROUGH THESE MODIFICATIONS, THERE IS INFINITE POTENTIAL FOR BENEFIT FOR THE FETUS, THE NEWBORN, AND THE INDIVIDUAL AS WELL AS POPULATION EFFECTS. ASSOCIATION WITH CV DISEASE, INCLUDING CORONARY HEART DISEASE AND PERIPHERAL VASCULAR DISEASE, IS EVIDENT THROUGH EPIGENETIC RELATIONSHIPS AND MODIFICATION BY MAJOR CV RISK FACTORS SUCH AS TOBACCO ABUSE. AGING ITSELF MAY BE ALTERED BY EPIGENETIC MODIFICATION. KNOWLEDGE OF EPIGENETICS AND ITS RELEVANCE TO THE DEVELOPMENT, MODIFICATION, AND PREVENTION OF CV DISEASE IS IN A VERY PRELIMINARY STAGE BUT HAS AN INFINITE FUTURE. 2015 16 705 29 BUILDING RISK-ON-A-CHIP MODELS TO IMPROVE BREAST CANCER RISK ASSESSMENT AND PREVENTION. PREVENTIVE ACTIONS FOR CHRONIC DISEASES HOLD THE PROMISE OF IMPROVING LIVES AND REDUCING HEALTHCARE COSTS. FOR SEVERAL DISEASES, INCLUDING BREAST CANCER, MULTIPLE RISK AND PROTECTIVE FACTORS HAVE BEEN IDENTIFIED BY EPIDEMIOLOGISTS. THE IMPACT OF MOST OF THESE FACTORS HAS YET TO BE FULLY UNDERSTOOD AT THE ORGANISM, TISSUE, CELLULAR AND MOLECULAR LEVELS. IMPORTANTLY, COMBINATIONS OF EXTERNAL AND INTERNAL RISK AND PROTECTIVE FACTORS INVOLVE COOPERATIVITY THUS, SYNERGIZING OR ANTAGONIZING DISEASE ONSET. MODELS ARE NEEDED TO MECHANISTICALLY DECIPHER CANCER RISKS UNDER DEFINED CELLULAR AND MICROENVIRONMENTAL CONDITIONS. HERE, WE BRIEFLY REVIEW BREAST CANCER RISK MODELS BASED ON 3D CELL CULTURE AND PROPOSE TO IMPROVE RISK MODELING WITH LAB-ON-A-CHIP APPROACHES. WE SUGGEST EPITHELIAL TISSUE POLARITY, DNA REPAIR AND EPIGENETIC PROFILES AS ENDPOINTS IN RISK ASSESSMENT MODELS AND DISCUSS THE DEVELOPMENT OF 'RISKS-ON-CHIPS' INTEGRATING BIOSENSORS OF THESE ENDPOINTS AND OF GENERAL TISSUE HOMEOSTASIS. RISKS-ON-CHIPS WILL HELP IDENTIFY BIOMARKERS OF RISK, SERVE AS SCREENING PLATFORMS FOR CANCER PREVENTIVE AGENTS, AND PROVIDE A BETTER UNDERSTANDING OF RISK MECHANISMS, HENCE RESULTING IN NOVEL DEVELOPMENTS IN DISEASE PREVENTION. 2013 17 3385 46 HOMEOSTATIC IMBALANCE AND COLON CANCER: THE DYNAMIC EPIGENETIC INTERPLAY OF INFLAMMATION, ENVIRONMENTAL TOXINS, AND CHEMOPREVENTIVE PLANT COMPOUNDS. THE ADVENT OF MODERN MEDICINE HAS ALLOWED FOR SIGNIFICANT ADVANCES WITHIN THE FIELDS OF EMERGENCY CARE, SURGERY, AND INFECTIOUS DISEASE CONTROL. HEALTH THREATS THAT WERE HISTORICALLY RESPONSIBLE FOR IMMEASURABLE TOLLS ON HUMAN LIFE ARE NOW ALL BUT ERADICATED WITHIN CERTAIN POPULATIONS, SPECIFICALLY THOSE THAT ENJOY HIGHER DEGREES OF SOCIO-ECONOMIC STATUS AND ACCESS TO HEALTHCARE. HOWEVER, MODERNIZATION AND ITS RESULTING LIFESTYLE TRENDS HAVE USHERED IN A NEW ERA OF CHRONIC ILLNESS; ONE IN WHICH AN UNPRECEDENTED NUMBER OF PEOPLE ARE ESTIMATED TO CONTRACT CANCER AND OTHER INFLAMMATORY DISEASES. HERE, WE EXPLORE THE IDEA THAT HOMEOSTASIS HAS BEEN REDEFINED WITHIN JUST A FEW GENERATIONS, AND THAT DISEASES SUCH AS COLORECTAL CANCER ARE THE RESULT OF FLUCTUATING PHYSIOLOGICAL AND MOLECULAR IMBALANCES. PHYTOCHEMICAL-DEPRIVED, PRO-INFLAMMATORY DIETS COMBINED WITH LOW-DOSE EXPOSURES TO ENVIRONMENTAL TOXINS, INCLUDING BISPHENOL-A (BPA) AND OTHER ENDOCRINE DISRUPTORS, ARE NOW LINKED TO INCREASING INCIDENCES OF CANCER IN WESTERNIZED SOCIETIES AND DEVELOPING COUNTRIES. THERE IS RECENT EVIDENCE THAT DISEASE DETERMINANTS ARE LIKELY SET IN UTERO AND FURTHER PERPETUATED INTO ADULTHOOD DEPENDENT UPON THE INNATE AND ENVIRONMENTALLY ACQUIRED PHENOTYPE UNIQUE TO EACH INDIVIDUAL. IN ORDER TO ADDRESS A DISEASE AS MULTI-FACTORIAL, CASE-SPECIFIC, AND REMARKABLY ADAPTIVE AS CANCER, RESEARCH MUST FOCUS ON ITS ROOT CAUSES IN ORDER TO ELUCIDATE THE MOLECULAR MECHANISMS BY WHICH THEY CAN BE PREVENTED OR COUNTERACTED VIA PLANT-DERIVED COMPOUNDS SUCH AS EPIGALLOCATECHIN-3-GALLATE (EGCG) AND RESVERATROL. THE SIGNIFICANT ROLE OF EPIGENETICS IN THE REGULATION OF THESE COMPLEX PROCESSES IS EMPHASIZED HERE TO FORM A COMPREHENSIVE VIEW OF THE DYNAMIC INTERACTIONS THAT INFLUENCE MODERN-DAY CARCINOGENESIS, AND HOW SENSIBLY RESTORING HOMEOSTATIC BALANCE MAY BE THE KEY TO THE CANCER RIDDLE. 2012 18 4794 40 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 19 3169 44 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 20 2528 32 EPIGENETICS AS A KEY LINK BETWEEN PSYCHOSOCIAL STRESS AND AGING: CONCEPTS, EVIDENCE, MECHANISMS . PSYCHOSOCIAL STRESS-ESPECIALLY WHEN CHRONIC, EXCESSIVE, OR OCCURRING EARLY IN LIFE-HAS BEEN ASSOCIATED WITH ACCELERATED AGING AND INCREASED DISEASE RISK. WITH RAPID AGING OF THE WORLD POPULATION, THE NEED TO ELUCIDATE THE UNDERLYING MECHANISMS IS PRESSING, NOW MORE SO THAN EVER. AMONG MOLECULAR MECHANISMS LINKING STRESS AND AGING, THE PRESENT ARTICLE REVIEWS EVIDENCE ON THE ROLE OF EPIGENETICS, BIOCHEMICAL PROCESSES THAT CAN BE SET INTO MOTION BY STRESSORS AND IN TURN INFLUENCE GENOMIC FUNCTION AND COMPLEX PHENOTYPES, INCLUDING AGING-RELATED OUTCOMES. THE ARTICLE FURTHER PROVIDES A CONCEPTUAL MECHANISTIC FRAMEWORK ON HOW STRESS MAY DRIVE EPIGENETIC CHANGES AT SUSCEPTIBLE GENOMIC SITES, THEREBY EXERTING SYSTEMS-LEVEL EFFECTS ON THE AGING EPIGENOME WHILE ALSO REGULATING THE EXPRESSION OF MOLECULES IMPLICATED IN AGING-RELATED PROCESSES. THIS EMERGING EVIDENCE, TOGETHER WITH WORK EXAMINING RELATED BIOLOGICAL PROCESSES, BEGINS TO SHED LIGHT ON THE EPIGENETIC AND, MORE BROADLY, MOLECULAR UNDERPINNINGS OF THE LONG-HYPOTHESIZED CONNECTION BETWEEN STRESS AND AGING. . 2019