1 2560 124 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 2 6204 47 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 3 5376 53 RECENT DEVELOPMENTS IN EPIGENETICS OF ACUTE AND CHRONIC KIDNEY DISEASES. THE GROWING EPIDEMIC OF OBESITY AND DIABETES, THE AGING POPULATION AS WELL AS PREVALENCE OF DRUG ABUSE HAS LED TO SIGNIFICANT INCREASES IN THE RATES OF THE CLOSELY ASSOCIATED ACUTE AND CHRONIC KIDNEY DISEASES, INCLUDING DIABETIC NEPHROPATHY. FURTHERMORE, EVIDENCE SHOWS THAT PARENTAL BEHAVIOR AND DIET CAN AFFECT THE PHENOTYPE OF SUBSEQUENT GENERATIONS VIA EPIGENETIC TRANSMISSION MECHANISMS. THESE DATA SUGGEST A STRONG INFLUENCE OF THE ENVIRONMENT ON DISEASE SUSCEPTIBILITY AND THAT, APART FROM GENETIC SUSCEPTIBILITY, EPIGENETIC MECHANISMS NEED TO BE EVALUATED TO GAIN CRITICAL NEW INFORMATION ABOUT KIDNEY DISEASES. EPIGENETICS IS THE STUDY OF PROCESSES THAT CONTROL GENE EXPRESSION AND PHENOTYPE WITHOUT ALTERATIONS IN THE UNDERLYING DNA SEQUENCE. EPIGENETIC MODIFICATIONS, INCLUDING CYTOSINE DNA METHYLATION AND COVALENT POST-TRANSLATIONAL MODIFICATIONS OF HISTONES IN CHROMATIN, ARE PART OF THE EPIGENOME, THE INTERFACE BETWEEN THE STABLE GENOME AND THE VARIABLE ENVIRONMENT. THIS DYNAMIC EPIGENETIC LAYER RESPONDS TO EXTERNAL ENVIRONMENTAL CUES TO INFLUENCE THE EXPRESSION OF GENES ASSOCIATED WITH DISEASE STATES. THE FIELD OF EPIGENETICS HAS SEEN REMARKABLE GROWTH IN THE PAST FEW YEARS WITH SIGNIFICANT ADVANCES IN BASIC BIOLOGY, CONTRIBUTIONS TO HUMAN DISEASE, AS WELL AS EPIGENOMICS TECHNOLOGIES. FURTHER UNDERSTANDING OF HOW THE RENAL CELL EPIGENOME IS ALTERED BY METABOLIC AND OTHER STIMULI CAN YIELD NOVEL NEW INSIGHTS INTO THE PATHOGENESIS OF KIDNEY DISEASES. IN THIS REVIEW, WE HAVE DISCUSSED THE CURRENT KNOWLEDGE ON THE ROLE OF EPIGENETIC MECHANISMS (PRIMARILY DNAME AND HISTONE MODIFICATIONS) IN ACUTE AND CHRONIC KIDNEY DISEASES, AND THEIR TRANSLATIONAL POTENTIAL TO IDENTIFY MUCH NEEDED NEW THERAPIES. 2015 4 1505 36 DNA METHYLATION AND HISTONE MODIFICATION IN HYPERTENSION. SYSTEMIC HYPERTENSION, WHICH EVENTUALLY RESULTS IN HEART FAILURE, RENAL FAILURE OR STROKE, IS A COMMON CHRONIC HUMAN DISORDER THAT PARTICULARLY AFFECTS ELDERS. ALTHOUGH MANY SIGNALING PATHWAYS INVOLVED IN THE DEVELOPMENT OF HYPERTENSION HAVE BEEN REPORTED OVER THE PAST DECADES, WHICH HAS LED TO THE IMPLEMENTATION OF A WIDE VARIETY OF ANTI-HYPERTENSIVE THERAPIES, ONE HALF OF ALL HYPERTENSIVE PATIENTS STILL DO NOT HAVE THEIR BLOOD PRESSURE CONTROLLED. THE FRONTIER IN UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING HYPERTENSION HAS NOW ADVANCED TO THE LEVEL OF EPIGENOMICS. PARTICULARLY, INCREASING EVIDENCE IS EMERGING THAT DNA METHYLATION AND HISTONE MODIFICATIONS PLAY AN IMPORTANT ROLE IN GENE REGULATION AND ARE INVOLVED IN ALTERATION OF THE PHENOTYPE AND FUNCTION OF VASCULAR CELLS IN RESPONSE TO ENVIRONMENTAL STRESSES. THIS REVIEW SEEKS TO HIGHLIGHT THE RECENT ADVANCES IN OUR KNOWLEDGE OF THE EPIGENETIC REGULATIONS AND MECHANISMS OF HYPERTENSION, FOCUSING ON THE ROLE OF DNA METHYLATION AND HISTONE MODIFICATION IN THE VASCULAR WALL. A BETTER UNDERSTANDING OF THE EPIGENOMIC REGULATION IN THE HYPERTENSIVE VESSEL MAY LEAD TO THE IDENTIFICATION OF NOVEL TARGET MOLECULES THAT, IN TURN, MAY LEAD TO NOVEL DRUG DISCOVERIES FOR THE TREATMENT OF HYPERTENSION. 2018 5 2562 38 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 6 2154 48 EPIGENETIC MECHANISMS AND KIDNEY DISEASES. IN RECENT YEARS, MOLECULAR RESEARCH HAS BROUGHT TO LIGHT A SERIES OF MECHANISMS INVOLVED IN THE REGULATION OF GENE FUNCTION WITHOUT ALTERING THE DNA SEQUENCE. THESE MECHANISMS ARE DESCRIBED WITH THE TERM "EPIGENETICS" AND INCLUDE MODIFICATIONS IN THE STRUCTURE OF THE HUMAN GENOME, LEADING TO HERITABLE AND POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION. THERE IS NOW INCREASING EVIDENCE SUGGESTING THAT SEVERAL CHARACTERISTIC FEATURES OF CHRONIC KIDNEY DISEASE SUCH AS HYPERHOMOCYSTEINEMIA, SUBCLINICAL INFLAMMATION, INCREASED OXIDATIVE STRESS AND OTHERS MAY AFFECT THE HUMAN EPIGENOME. IN ADDITION, ANIMAL STUDIES HAVE SUGGESTED A POSSIBLE LINK BETWEEN NUTRITION AND ENVIRONMENTAL EXPOSURE DURING THE PERICONCEPTIONAL PERIOD AND EPIGENETIC CHANGES IN THE EXPRESSION OF MAJOR GENES IMPLICATED IN KIDNEY ORGANOGENESIS; THESE CHANGES RESULT IN A DIMINISHED NUMBER OF NEPHRONS IN THE DEVELOPING KIDNEY, WHICH PREDISPOSES TO AN INCREASED RISK FOR HYPERTENSION AND CHRONIC KIDNEY DISEASE IN FUTURE LIFE. THE UNDERSTANDING OF THE ROLE OF EPIGENETIC PHENOMENA IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE OPENS NEW AVENUES FOR FUTURE THERAPEUTIC STRATEGIES, THROUGH THE DEVELOPMENT OF PHARMACEUTICAL AGENTS THAT TARGET DIRECTLY WITH THE CHANGES IN THE HUMAN EPIGENOME. SUCH EPIGENETIC DRUGS ARE ALREADY IN CLINICAL USE FOR THE TREATMENT OF CANCER AS WELL AS UNDER INVESTIGATION FOR THE USE IN OTHER DISEASES. THIS REVIEW WILL SUMMARIZE THE EXISTING DATA ON THE LINK BETWEEN EPIGENETIC MECHANISMS AND CHRONIC UREMIC MILIEU, AS WELL AS THE PROMISING RESULTS OF ONGOING RESEARCH IN THE FIELD OF EPIGENETIC DRUGS THAT COULD REPRESENT ADDITIONAL OPTIONS IN OUR THERAPEUTIC ARMAMENTARIUM FOR PATIENTS WITH CHRONIC KIDNEY DISEASE. 2011 7 2163 39 EPIGENETIC MECHANISMS IN DIABETIC VASCULAR COMPLICATIONS. THERE HAS BEEN A RAPID INCREASE IN THE INCIDENCE OF DIABETES AS WELL THE ASSOCIATED VASCULAR COMPLICATIONS. BOTH GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN IMPLICATED IN THESE PATHOLOGIES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT. ACTIONS OF MAJOR PATHOLOGICAL MEDIATORS OF DIABETES AND ITS COMPLICATIONS SUCH AS HYPERGLYCAEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS CAN LEAD TO DYSREGULATED EPIGENETIC MECHANISMS THAT AFFECT CHROMATIN STRUCTURE AND GENE EXPRESSION. FURTHERMORE, PERSISTENCE OF THIS ALTERED STATE OF THE EPIGENOME MAY BE THE UNDERLYING MECHANISM CONTRIBUTING TO A 'METABOLIC MEMORY' THAT RESULTS IN CHRONIC INFLAMMATION AND VASCULAR DYSFUNCTION IN DIABETES EVEN AFTER ACHIEVING GLYCAEMIC CONTROL. FURTHER EXAMINATION OF EPIGENETIC MECHANISMS BY ALSO TAKING ADVANTAGE OF RECENTLY DEVELOPED NEXT-GENERATION SEQUENCING TECHNOLOGIES CAN PROVIDE NOVEL INSIGHTS INTO THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS AND LEAD TO THE DISCOVERY OF MUCH NEEDED NEW DRUG TARGETS FOR THESE DISEASES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF EPIGENETICS IN DIABETES AND ITS VASCULAR COMPLICATIONS, AND RECENT TECHNOLOGICAL ADVANCES THAT HAVE SIGNIFICANTLY ACCELERATED THE FIELD. 2011 8 1871 44 EMERGING ROLE OF EPIGENETICS IN EXPLAINING RELATIONSHIP OF PERIODONTITIS AND CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES SUCH AS ISCHEMIC HEART DISEASES OR STROKE ARE AMONG THE LEADING CAUSE OF DEATHS GLOBALLY, AND EVIDENCE SUGGESTS THAT THESE DISEASES ARE MODULATED BY A MULTIFACTORIAL AND COMPLEX INTERPLAY OF GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. GENETIC PREDISPOSITION AND CHRONIC EXPOSURE TO MODIFIABLE RISK FACTORS HAVE BEEN EXPLORED TO BE INVOLVED IN THE PATHOPHYSIOLOGY OF CVD. ENVIRONMENTAL FACTORS CONTRIBUTE TO AN INDIVIDUAL'S PROPENSITY TO DEVELOP MAJOR CARDIOVASCULAR RISK FACTORS THROUGH EPIGENETIC MODIFICATIONS OF DNA AND HISTONES VIA MIRNA REGULATION OF PROTEIN TRANSLATION THAT ARE TYPES OF EPIGENETIC MECHANISMS AND PARTICIPATE IN DISEASE DEVELOPMENT. PERIODONTAL DISEASE (PD) IS ONE OF THE MOST COMMON ORAL DISEASES IN HUMANS THAT IS CHARACTERIZED BY LOW-GRADE INFLAMMATION AND HAS BEEN SHOWN TO INCREASE THE RISK OF CVDS. RISK FACTORS INVOLVED IN PD AND CVD ARE DETERMINED BOTH GENETICALLY AND BEHAVIORALLY. PERIODONTAL DISEASES SUCH AS CHRONIC INFLAMMATION PROMOTE DNA METHYLATION. EPIGENETIC MODIFICATIONS INVOLVED IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS PLAY AN ESSENTIAL ROLE IN PLAQUE DEVELOPMENT AND VULNERABILITY. EPIGENETICS HAS OPENED A NEW WORLD TO UNDERSTAND AND MANAGE HUMAN DISEASES, INCLUDING CVDS AND PERIODONTAL DISEASES. GENETIC MEDICINE HAS STARTED A NEW ERA OF EPIGENETICS TO OVERCOME HUMAN DISEASES WITH VARIOUS NEW METHODOLOGY. EPIGENETIC PROFILING MAY AID IN BETTER DIAGNOSIS AND STRATIFICATION OF PATIENTS SHOWING POTENTIAL PREDISPOSED STATES FOR DISEASE. A BETTER UNDERSTANDING OF THE EXACT REGULATORY MECHANISMS OF EPIGENETIC PATHWAYS DRIVING INFLAMMATION IS SLOWLY EMERGING AND WILL AID IN DEVELOPING NOVEL TOOLS FOR THE TREATMENT OF DISEASE. 2021 9 1060 38 CLINICAL RELEVANCE OF EPIGENETIC DYSREGULATION IN CHRONIC KIDNEY DISEASE-ASSOCIATED CARDIOVASCULAR DISEASE. ACROSS THE SPECTRUM OF CLINICAL MEDICINE, THE FIELD OF EPIGENETICS HAS GAINED SUBSTANTIAL SCIENTIFIC INTEREST IN RECENT YEARS. EPIGENETICS REFERS TO MODIFICATIONS IN GENE EXPRESSION WHICH ARE NOT EXPLAINED BY CHANGES IN DNA SEQUENCE. CLASSICAL COMPONENTS OF EPIGENETIC REGULATION COMPRISE DNA METHYLATION, HISTONE MODIFICATIONS AND RNA INTERFERENCE. IN CHRONIC KIDNEY DISEASE (CKD), SEVERAL FEATURES OF URAEMIA, SUCH AS HYPERHOMOCYSTEINEMIA AND INFLAMMATION, MAY CONTRIBUTE TO CHANGES IN EPIGENETIC GENE REGULATION. IT HAS BEEN SUGGESTED THAT THESE CHANGES MAY AFFECT GENES RELATED TO CARDIOVASCULAR DISEASE. THEREBY, A URAEMIA-ASSOCIATED DISTURBANCE IN EPIGENETIC REGULATION MAY CONTRIBUTE TO THE SUBSTANTIAL INCREASE IN CARDIOVASCULAR MORBIDITY IN CKD PATIENTS. THE PRESENT REVIEW AIMS TO SUMMARIZE CURRENT KNOWLEDGE OF EPIGENETIC DYSREGULATION IN CARDIOVASCULAR DISEASE FROM A NEPHROLOGICAL PERSPECTIVE, WITH A SPECIAL FOCUS ON DNA METHYLATION. WE FIRST DESCRIBE THE IMPACT OF ALTERED EPIGENETIC REGULATION IN NON-CKD-ASSOCIATED ARTERIOSCLEROSIS, AND NEXT CHARACTERIZE URAEMIC FEATURES WHICH MAY AFFECT EPIGENETIC GENE REGULATION IN THE CONTEXT OF CARDIOVASCULAR DISEASE. FINALLY, WE CONCLUDE THAT SUBSTANTIAL ADDITIONAL WORK IS NEEDED BEFORE EPIGENETIC REGULATORY MECHANISMS MAY BECOME THERAPEUTIC TARGETS IN CKD-ASSOCIATED CARDIOVASCULAR DISEASE. 2013 10 6812 50 [EPIGENETICS, INTERFACE BETWEEN ENVIRONMENT AND GENES: ROLE IN COMPLEX DISEASES]. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION OR CELLULAR PHENOTYPE CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. EPIGENETICS IS ONE OF THE MAJOR MECHANISMS EXPLAINING THE "DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASES" (DOHAD). BESIDES GENETIC BACKGROUND INHERITED FROM PARENTS, WHICH CONFERS SUSCEPTIBILITY TO CERTAIN PATHOLOGIES, EPIGENETIC CHANGES CONSTITUTE THE MEMORY OF PREVIOUS EVENTS, EITHER POSITIVE OR NEGATIVE, ALONG THE LIFE CYCLE, INCLUDING AT THE IN UTERO STAGE. THE LATER EXPOSITION TO HOSTILE ENVIRONMENT MAY REVEAL SUCH SUSCEPTIBILITY, WITH THE DEVELOPMENT OF VARIOUS PATHOLOGIES, AMONG THEM NUMEROUS CHRONIC COMPLEX DISEASES. THE DEMONSTRATION OF SUCH A SEQUENCE OF EVENTS HAS BEEN SHOWN FOR METABOLIC DISEASES AS OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES, CARDIOVASCULAR DISEASE AND CANCER. IN CONTRAST TO GENETIC PREDISPOSITION, WHICH IS IRREVERSIBLE, EPIGENETIC CHANGES ARE POTENTIALLY REVERSIBLE, THUS GIVING TARGETS NOT ONLY FOR PREVENTION, BUT POSSIBLY ALSO FOR THE TREATMENT OF CERTAIN COMPLEX DISEASES. 2012 11 5069 36 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 12 34 37 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 13 3404 44 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 14 4192 37 METABOLIC MEMORY AND CHRONIC DIABETES COMPLICATIONS: POTENTIAL ROLE FOR EPIGENETIC MECHANISMS. RECENT ESTIMATES INDICATE THAT DIABETES MELLITUS CURRENTLY AFFECTS MORE THAN 10 % OF THE WORLD'S POPULATION. EVIDENCE FROM BOTH THE LABORATORY AND LARGE SCALE CLINICAL TRIALS HAS REVEALED THAT PROLONGED HYPERGLYCEMIA INDUCES CHRONIC COMPLICATIONS WHICH PERSIST AND PROGRESS UNIMPEDED EVEN WHEN GLYCEMIC CONTROL IS PHARMACEUTICALLY ACHIEVED VIA THE PHENOMENON OF METABOLIC MEMORY. THE EPIGENOME IS COMPRISED OF ALL CHROMATIN MODIFICATIONS INCLUDING POST TRANSLATIONAL HISTONE MODIFICATION, EXPRESSION CONTROL VIA MIRNAS AND THE METHYLATION OF CYTOSINE WITHIN DNA. MODIFICATIONS OF THESE EPIGENETIC MARKS NOT ONLY ALLOW CELLS AND ORGANISMS TO QUICKLY RESPOND TO CHANGING ENVIRONMENTAL STIMULI BUT ALSO CONFER THE ABILITY OF THE CELL TO "MEMORIZE" THESE ENCOUNTERS. AS SUCH, THESE PROCESSES HAVE GAINED MUCH ATTENTION AS POTENTIAL MOLECULAR MECHANISMS UNDERLYING METABOLIC MEMORY AND CHRONIC DIABETIC COMPLICATIONS. HERE WE PRESENT A REVIEW OF THE VERY RECENT LITERATURE PUBLISHED PERTAINING TO THIS SUBJECT. 2012 15 2807 31 FETAL PROGRAMMING OF CHRONIC KIDNEY DISEASE: THE ROLE OF MATERNAL SMOKING, MITOCHONDRIAL DYSFUNCTION, AND EPIGENETIC MODFIFICATION. THE ROLE OF AN ADVERSE IN UTERO ENVIRONMENT IN THE PROGRAMMING OF CHRONIC KIDNEY DISEASE IN THE ADULT OFFSPRING IS INCREASINGLY RECOGNIZED. THE CELLULAR AND MOLECULAR MECHANISMS LINKING THE IN UTERO ENVIRONMENT AND FUTURE DISEASE SUSCEPTIBILITY REMAIN UNKNOWN. MATERNAL SMOKING IS A COMMON MODIFIABLE ADVERSE IN UTERO EXPOSURE, POTENTIALLY ASSOCIATED WITH BOTH MITOCHONDRIAL DYSFUNCTION AND EPIGENETIC MODIFICATION IN THE OFFSPRING. WHILE STUDIES ARE EMERGING THAT POINT TOWARD A KEY ROLE OF MITOCHONDRIAL DYSFUNCTION IN ACUTE AND CHRONIC KIDNEY DISEASE, IT MAY HAVE ITS ORIGIN IN EARLY DEVELOPMENT, BECOMING CLINICALLY APPARENT WHEN SECONDARY INSULTS OCCUR. ABERRANT EPIGENETIC PROGRAMMING MAY ADD AN ADDITIONAL LAYER OF COMPLEXITY TO ORCHESTRATE FIBROGENESIS IN THE KIDNEY AND SUSCEPTIBILITY TO CHRONIC KIDNEY DISEASE IN LATER LIFE. IN THIS REVIEW, WE EXPLORE THE EVIDENCE FOR MITOCHONDRIAL DYSFUNCTION AND EPIGENETIC MODIFICATION THROUGH ABERRANT DNA METHYLATION AS KEY MECHANISTIC ASPECTS OF FETAL PROGRAMMING OF CHRONIC KIDNEY DISEASE AND DISCUSS THEIR POTENTIAL USE IN DIAGNOSTICS AND TARGETS FOR THERAPY. 2015 16 2491 32 EPIGENETICS AND CARDIOVASCULAR DISEASE IN DIABETES. TYPE 2 DIABETES HAS BECOME A MAJOR HEALTH ISSUE WORLDWIDE. CHRONIC HYPERGLYCEMIA INDUCES A LOW-GRADE INFLAMMATION THAT, ON TOP OF OTHER MECHANISMS, LEADS TO ENDOTHELIAL DYSFUNCTION. MOUNTING EVIDENCE SUGGESTS THAT DNA METHYLATION, POST-TRANSLATIONAL MODIFICATIONS OF HISTONES, AND LONG NON-CODING RNAS PLAY AN IMPORTANT ROLE IN THE INITIATION, MAINTENANCE, AND PROGRESSION OF BOTH MACRO- AND MICRO-VASCULAR COMPLICATIONS OF DIABETES. LONG-TERM EXPOSURE TO HYPERGLYCEMIA INDUCES EPIGENETIC CHANGES THAT COULD BECOME IRREVERSIBLE, A PHENOMENON KNOWN AS THE 'METABOLIC MEMORY.' WHETHER EPIGENETIC-BASED THERAPIES COULD BE USED TO SLOW OR LIMIT THE PROGRESSION OF CARDIOVASCULAR DISEASE REMAINS UNCLEAR. WHILE NON-CODING RNAS ARE CURRENTLY INVESTIGATED AS POTENTIAL BIOMARKERS THAT PREDICT DIABETIC CARDIOVASCULAR DISEASE INCIDENCE AND PROGRESSION, THEIR THERAPEUTIC ROLE IS ONLY HYPOTHETICAL. IN THIS REVIEW, WE HIGHLIGHT THE LATEST FINDINGS IN EXPERIMENTAL AND CLINICAL STUDIES RELEVANT TO EPIGENETICS AND CARDIOVASCULAR DISEASE IN DIABETES. 2015 17 2049 24 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 18 2136 40 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 19 1405 41 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 20 6378 45 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