1 5951 92 TARGETING THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM TO PREVENT HYPERTENSION AND KIDNEY DISEASE OF DEVELOPMENTAL ORIGINS. THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS) IS IMPLICATED IN HYPERTENSION AND KIDNEY DISEASE. THE DEVELOPING KIDNEY CAN BE PROGRAMMED BY VARIOUS EARLY-LIFE INSULTS BY SO-CALLED RENAL PROGRAMMING, RESULTING IN HYPERTENSION AND KIDNEY DISEASE IN ADULTHOOD. THIS THEORY IS KNOWN AS DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). CONVERSELY, EARLY RAAS-BASED INTERVENTIONS COULD REVERSE PROGRAM PROCESSES TO PREVENT A DISEASE FROM OCCURRING BY SO-CALLED REPROGRAMMING. IN THE CURRENT REVIEW, WE MAINLY SUMMARIZE (1) THE CURRENT KNOWLEDGE ON THE RAAS IMPLICATED IN RENAL PROGRAMMING; (2) CURRENT EVIDENCE SUPPORTING THE CONNECTIONS BETWEEN THE ABERRANT RAAS AND OTHER MECHANISMS BEHIND RENAL PROGRAMMING, SUCH AS OXIDATIVE STRESS, NITRIC OXIDE DEFICIENCY, EPIGENETIC REGULATION, AND GUT MICROBIOTA DYSBIOSIS; AND (3) AN OVERVIEW OF HOW RAAS-BASED REPROGRAMMING INTERVENTIONS MAY PREVENT HYPERTENSION AND KIDNEY DISEASE OF DEVELOPMENTAL ORIGINS. TO ACCELERATE THE TRANSITION OF RAAS-BASED INTERVENTIONS FOR PREVENTION OF HYPERTENSION AND KIDNEY DISEASE, AN EXTENDED COMPREHENSION OF THE RAAS IMPLICATED IN RENAL PROGRAMMING IS NEEDED, AS WELL AS A GREATER FOCUS ON FURTHER CLINICAL TRANSLATION. 2021 2 2807 25 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 3 2693 25 EVOLUTION, KIDNEY DEVELOPMENT, AND CHRONIC KIDNEY DISEASE. THERE IS A GLOBAL EPIDEMIC OF CHRONIC KIDNEY DISEASE (CKD) CHARACTERIZED BY A PROGRESSIVE LOSS OF NEPHRONS, ASCRIBED IN LARGE PART TO A RISING INCIDENCE OF HYPERTENSION, METABOLIC SYNDROME, AND TYPE 2 DIABETES MELLITUS. THERE IS A TEN-FOLD VARIATION IN NEPHRON NUMBER AT BIRTH IN THE GENERAL POPULATION, AND A 50% OVERALL DECREASE IN NEPHRON NUMBER IN THE LAST DECADES OF LIFE. THE VICIOUS CYCLE OF NEPHRON LOSS STIMULATING HYPERTROPHY BY REMAINING NEPHRONS AND RESULTING IN GLOMERULOSCLEROSIS HAS BEEN REGARDED AS MALADAPTIVE, AND ONLY PARTIALLY RESPONSIVE TO ANGIOTENSIN INHIBITION. ADVANCES OVER THE PAST CENTURY IN KIDNEY PHYSIOLOGY, GENETICS, AND DEVELOPMENT HAVE ELUCIDATED MANY ASPECTS OF NEPHRON FORMATION, STRUCTURE AND FUNCTION. PARALLEL ADVANCES HAVE BEEN ACHIEVED IN EVOLUTIONARY BIOLOGY, WITH THE EMERGENCE OF EVOLUTIONARY MEDICINE, A DISCIPLINE THAT PROMISES TO PROVIDE NEW INSIGHT INTO THE TREATMENT OF CHRONIC DISEASE. THIS REVIEW PROVIDES A FRAMEWORK FOR UNDERSTANDING THE ORIGINS OF CONTEMPORARY DEVELOPMENTAL NEPHROLOGY, AND RECENT PROGRESS IN EVOLUTIONARY BIOLOGY. THE ESTABLISHMENT OF EVOLUTIONARY DEVELOPMENTAL BIOLOGY (EVO-DEVO), ECOLOGICAL DEVELOPMENTAL BIOLOGY (ECO-DEVO), AND DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) FOLLOWED THE DISCOVERY OF THE HOX GENE FAMILY, THE RECOGNITION OF THE CONTRIBUTION OF CUMULATIVE ENVIRONMENTAL STRESSORS TO THE CHANGING PHENOTYPE OVER THE LIFE CYCLE, AND MECHANISMS OF EPIGENETIC REGULATION. THE MATURATION OF EVOLUTIONARY MEDICINE HAS CONTRIBUTED TO NEW INVESTIGATIVE APPROACHES TO CARDIOVASCULAR DISEASE, CANCER, AND INFECTIOUS DISEASE, AND PROMISES THE SAME FOR CKD. BY INCORPORATING THESE PRINCIPLES, DEVELOPMENTAL NEPHROLOGY IS IDEALLY POSITIONED TO ANSWER IMPORTANT QUESTIONS REGARDING THE FATE OF NEPHRONS FROM EMBRYO THROUGH SENESCENCE. 2019 4 1366 33 DEVELOPMENTAL ORIGINS OF CHRONIC KIDNEY DISEASE: SHOULD WE FOCUS ON EARLY LIFE? CHRONIC KIDNEY DISEASE (CKD) IS BECOMING A GLOBAL BURDEN, DESPITE RECENT ADVANCES IN MANAGEMENT. CKD CAN BEGIN IN EARLY LIFE BY SO-CALLED "DEVELOPMENTAL PROGRAMMING" OR "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD). EARLY-LIFE INSULTS CAUSE STRUCTURAL AND FUNCTIONAL CHANGES IN THE DEVELOPING KIDNEY, WHICH IS CALLED RENAL PROGRAMMING. EPIDEMIOLOGICAL AND EXPERIMENTAL EVIDENCE SUPPORTS THE PROPOSITION THAT EARLY-LIFE ADVERSE EVENTS LEAD TO RENAL PROGRAMMING AND MAKE SUBJECTS VULNERABLE TO DEVELOPING CKD AND ITS COMORBIDITIES IN LATER LIFE. IN ADDITION TO LOW NEPHRON ENDOWMENT, SEVERAL MECHANISMS HAVE BEEN PROPOSED FOR RENAL PROGRAMMING. THE DOHAD CONCEPT OPENS A NEW WINDOW TO OFFSET THE PROGRAMMING PROCESS IN EARLY LIFE TO PREVENT THE DEVELOPMENT OF ADULT KIDNEY DISEASE, NAMELY REPROGRAMMING. HERE, WE REVIEW THE KEY THEMES ON THE DEVELOPMENTAL ORIGINS OF CKD. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: EVIDENCE FROM HUMAN STUDIES SUPPORT FETAL PROGRAMMING OF KIDNEY DISEASE; INSIGHT FROM ANIMAL MODELS OF RENAL PROGRAMMING; HYPOTHETICAL MECHANISMS OF RENAL PROGRAMMING; ALTERATIONS OF RENAL TRANSCRIPTOME IN RESPONSE TO EARLY-LIFE INSULTS; AND THE APPLICATION OF REPROGRAMMING INTERVENTIONS TO PREVENT THE PROGRAMMING OF KIDNEY DISEASE. 2017 5 4456 22 MOLECULAR MECHANISMS IN RENAL DEGENERATIVE DISEASE. CHRONIC KIDNEY DISEASE (CKD) HAS BECOME A MAJOR PUBLIC HEALTH PROBLEM WORLDWIDE. THEREFORE, A CONSIDERABLE EFFORT IS CURRENTLY DIRECTED TO UNDERSTAND THE MOLECULAR MECHANISMS OF RENAL DEGENERATIVE PROCESSES. REGARDLESS OF THEIR INITIATING CAUSE, ALL CHRONIC KIDNEY DISEASES (CKD) DEVELOP AT SOME LEVEL ORGAN FIBROSIS THAT INTERFERES WITH KIDNEY FUNCTION. THIS IS ALSO TRUE FOR THE TWO MOST COMMON INHERITED CKD SYNDROMES, NEPHRONOPHTHITIS AND POLYCYSTIC KIDNEY DISEASE, WHOSE PRIMARY DEFECTS RESIDE WITHIN THE CILIUM OF KIDNEY EPITHELIAL CELLS. A COHORT OF ELEGANT RECENT STUDIES HAS ELICITED THE ROLE OF THE PRIMARY CILIUM AS A VERSATILE MECHANOSENSORY ORGANELLE THAT ALSO MIGHT COORDINATE CROSS-TALK BETWEEN MULTIPLE SIGNALING PATHWAYS. IN ADDITION, EPIGENETIC MECHANISMS ARE NOW REALIZED TO BE ESSENTIAL IN THE MAINTENANCE OF ADULT RENAL ARCHITECTURE. IN THIS REVIEW, WE WILL DISCUSS RECENT ADVANCES IN OUR UNDERSTANDING OF THE SIGNALING SYSTEMS IMPLICATED IN KIDNEY HOMEOSTASIS AND REPAIR. 2010 6 4719 25 NONCODING RNA AND EPIGENETIC GENE REGULATION IN RENAL DISEASES. KIDNEYS HAVE A MAJOR ROLE IN NORMAL PHYSIOLOGY AND METABOLIC HOMEOSTASIS. LOSS OR IMPAIRMENT OF KIDNEY FUNCTION IS A COMMON OCCURRENCE IN SEVERAL METABOLIC DISORDERS, INCLUDING HYPERTENSION AND DIABETES. CHRONIC KIDNEY DISEASE (CKD) AFFECT NEARLY 10% OF THE POPULATION WORLDWIDE; RANKS 18TH IN THE LIST OF CAUSES OF DEATH; AND CONTRIBUTES TO A SIGNIFICANT PROPORTION OF HEALTHCARE COSTS. THE TISSUE REPAIR AND REGENERATIVE POTENTIAL OF KIDNEYS ARE LIMITED AND THEY DECLINE DURING AGING. RECENT STUDIES HAVE DEMONSTRATED A KEY ROLE FOR EPIGENETIC PROCESSES AND PLAYERS, SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, NONCODING (NC)RNA, AND SO ON, IN BOTH KIDNEY DEVELOPMENT AND DISEASE. IN THIS REVIEW, WE HIGHLIGHT THESE RECENT FINDINGS WITH AN EMPHASIS ON ABERRANT EPIGENETIC CHANGES THAT ACCOMPANY RENAL DISEASES, KEY TARGETS, AND THEIR THERAPEUTIC VALUE. 2017 7 220 39 ACUTE KIDNEY DISEASE: AN OVERVIEW OF THE EPIDEMIOLOGY, PATHOPHYSIOLOGY, AND MANAGEMENT. ACUTE KIDNEY INJURY (AKI) INCREASES THE RISK OF CHRONIC KIDNEY DISEASE (CKD), AND AKI AND CKD ARE SEEN AS INTERCONNECTED SYNDROMES. ACUTE KIDNEY DISEASE (AKD) IS DEFINED AS SUBACUTE DAMAGE AND/OR LOSS OF KIDNEY FUNCTION OCCURRING 7 TO 90 DAYS AFTER AKI, DURING WHICH PERIOD KEY INTERVENTIONS MAY BE INITIATED TO HINDER THE DEVELOPMENT OF CKD. WHILE AKD IS USUALLY UNDER-RECOGNIZED, IT IS ASSOCIATED WITH HIGH MORBIDITY AND MORTALITY GLOBALLY. THIS REVIEW ARTICLE AIMS TO SUMMARIZE THE CURRENT KNOWLEDGE CONCERNING THE EPIDEMIOLOGY, PATHOPHYSIOLOGY, AND MANAGEMENT OF AKD WITH THE AIM TO DEVELOP MONITORING STRATEGIES AND THERAPEUTIC AGENTS OF AKD. GENERALLY, AKD TENDS TO OCCUR MORE FREQUENTLY IN THE ELDERLY AND THOSE WITH CHRONIC DISEASES, SUCH AS HYPERTENSION, DIABETES MELLITUS, AND METABOLIC SYNDROME. IN ADDITION, THE SEVERITY, DURATION, AND FREQUENCY OF AKI ARE INDEPENDENT RISK FACTORS FOR AKD. INVESTIGATIONS OF SEVERAL MECHANISMS OF AKD, SUCH AS RENAL TUBULAR EPITHELIUM CELL-CYCLE ARREST, EPIGENETIC CHANGE, CHRONIC INFLAMMATION, MITOCHONDRIA DYSFUNCTION, FAILED REGENERATION OF TUBULAR CELLS, METABOLIC REPROGRAMMING, AND RENIN-ANGIOTENSIN SYSTEM (RAS) ACTIVATION, HAVE IDENTIFIED ADDITIONAL POTENTIAL PHARMACOTHERAPY TARGETS. MANAGEMENT OF AKD INCLUDES PREVENTION OF REPEATED AKI, EARLY AND REGULAR FOLLOW-UP BY A NEPHROLOGIST, RESUMPTION AND ADJUSTMENT OF ESSENTIAL MEDICATION, OPTIMIZATION OF BLOOD PRESSURE CONTROL AND NUTRITION MANAGEMENT, AND DEVELOPMENT OF NEW PHARMACEUTICAL AGENTS INCLUDING RAS INHIBITORS. FINALLY, WE OUTLINE A CARE BUNDLE FOR AKD PATIENTS BASED ON IMPORTANT LESSONS LEARNED FROM STUDIES AND REGISTRIES AND IDENTIFY THE NEED FOR CLINICAL TRIALS OF RAS INHIBITORS OR OTHER NOVEL AGENTS TO IMPEDE ENSUING CKD DEVELOPMENT. 2023 8 5247 21 PROGRAMMED ADULT KIDNEY DISEASE: IMPORTANCE OF FETAL ENVIRONMENT. THE BARKER HYPOTHESIS STRONGLY SUPPORTED THE INFLUENCE OF FETAL ENVIRONMENT ON THE DEVELOPMENT OF CHRONIC DISEASES IN LATER LIFE. MULTIPLE EXPERIMENTAL AND HUMAN STUDIES HAVE IDENTIFIED THAT THE DELETERIOUS EFFECT OF FETAL PROGRAMMING COMMONLY LEADS TO ALTERATIONS IN RENAL DEVELOPMENT. THE INTERPLAY BETWEEN ENVIRONMENTAL INSULTS AND FETAL GENOME CAN INDUCE EPIGENETIC CHANGES AND LEAD TO ALTERATIONS IN THE EXPRESSION OF RENAL PHENOTYPE. IN THIS REVIEW, WE HAVE EXPLORED THE RENAL DEVELOPMENT AND ITS FUNCTIONS, WHILE FOCUSING ON THE EPIGENETIC FINDINGS AND FUNCTIONAL ASPECTS OF THE RENIN-ANGIOTENSIN SYSTEM AND ITS COMPONENTS. 2020 9 1515 29 DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS A GLOBAL EPIDEMIC, AND ITS MAJOR RISK FACTORS INCLUDE OBESITY AND TYPE 2 DIABETES. OBESITY NOT ONLY PROMOTES METABOLIC DYSREGULATION AND THE DEVELOPMENT OF DIABETIC KIDNEY DISEASE BUT ALSO MAY INDEPENDENTLY LEAD TO CKD BY A VARIETY OF MECHANISMS, INCLUDING ENDOCRINE AND METABOLIC DYSFUNCTION, INFLAMMATION, OXIDATIVE STRESS, ALTERED RENAL HEMODYNAMICS, AND LIPOTOXICITY. DELETERIOUS RENAL EFFECTS OF OBESITY CAN ALSO BE TRANSMITTED FROM ONE GENERATION TO THE NEXT, AND IT IS INCREASINGLY RECOGNIZED THAT OFFSPRING OF OBESE MOTHERS ARE PREDISPOSED TO CKD. EPIGENETIC MODIFICATIONS ARE CHANGES THAT REGULATE GENE EXPRESSION WITHOUT ALTERING THE DNA SEQUENCE. OF THESE, DNA METHYLATION IS THE MOST STUDIED. EPIGENETIC IMPRINTS, PARTICULARLY DNA METHYLATION, ARE LAID DOWN DURING CRITICAL PERIODS OF FETAL DEVELOPMENT, AND THEY MAY PROVIDE A MECHANISM BY WHICH MATERNAL-FETAL TRANSMISSION OF CHRONIC DISEASE OCCURS. OUR CURRENT REVIEW EXPLORES THE EVIDENCE FOR THE ROLE OF DNA METHYLATION IN THE DEVELOPMENT OF CKD, DIABETIC KIDNEY DISEASE, DIABETES, AND OBESITY. DNA METHYLATION HAS BEEN IMPLICATED IN RENAL FIBROSIS-THE FINAL PATHOPHYSIOLOGIC PATHWAY IN THE DEVELOPMENT OF END-STAGE KIDNEY DISEASE-WHICH SUPPORTS THE NOTION THAT DEMETHYLATING AGENTS MAY PLAY A POTENTIAL THERAPEUTIC ROLE IN PREVENTING DEVELOPMENT AND PROGRESSION OF CKD.-LARKIN, B. P., GLASTRAS, S. J., CHEN, H., POLLOCK, C. A., SAAD, S. DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. 2018 10 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 11 1934 25 ENVIRONMENTAL ORIGINS OF HYPERTENSION: PHYLOGENY, ONTOGENY AND EPIGENETICS. HYPERTENSION AND RENAL PARENCHYMAL DISEASE ARE INTRICATELY LINKED. PRIMARY RENAL PARENCHYMAL DISEASE CAN IMPACT ON SODIUM AND VOLUME REGULATION AND LEAD TO HYPERTENSION, WHILE ARTERIAL HYPERTENSION CAN INDUCE RENAL PARENCHYMAL INJURY AND PRECIPITATE RENAL DYSFUNCTION. THE EXAMINATION FOR CLUES TO THE ENVIRONMENTAL ORIGINS OF RENAL DISEASE AND HYPERTENSION NECESSITATES AN APPROACH THAT INTEGRATES EPIDEMIOLOGY, CLINICAL MEDICINE, DEVELOPMENTAL BIOLOGY, ENVIRONMENTAL SCIENCE AND EPIGENETICS, SUCH THAT THE MANNER IN WHICH GENES AND THE ENVIRONMENT INTERACT CAN BE BETTER UNDERSTOOD TO PAVE THE WAY FOR INNOVATIVE MANAGEMENT PARADIGMS WITH REGARDS TO PREVENTION, DIAGNOSIS AND TREATMENT. THIS REVIEW SUMMARIZES THE EXTANT LITERATURE AND PROVIDES COGENT ARGUMENTS FOR THE NEED TO EVALUATE CHRONIC ADULT ONSET DISEASE MODELS SUCH AS HYPERTENSION AND RENAL DISEASE FROM THE MODERN PERSPECTIVE THAT TAKES INTO ACCOUNT PRENATAL EXPOSURES, THE INTRAUTERINE ENVIRONMENT AND DEVELOPMENT, POSTNATAL GROWTH AND TRANSGENERATIONAL EPIGENETIC MODIFICATIONS WITH THEIR ATTENDANT FUTURE DISEASE RISK FROM THE INDIVIDUAL TO THE POPULATION LEVEL. 2015 12 1992 23 EPIGENETIC AND DEVELOPMENTAL INFLUENCES ON THE RISK OF OBESITY, DIABETES, AND METABOLIC SYNDROME. METABOLIC SYNDROME IS A GROWING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. METABOLIC SYNDROME IS CHARACTERIZED BY THE PRESENCE OF A VARIETY OF METABOLIC DISTURBANCES INCLUDING OBESITY, HYPERLIPIDEMIA, HYPERTENSION, AND ELEVATED FASTING BLOOD SUGAR. ALTHOUGH THE RISK FOR METABOLIC SYNDROME HAS LARGELY BEEN ATTRIBUTED TO ADULT LIFESTYLE FACTORS SUCH AS POOR NUTRITION, LACK OF EXERCISE, AND SMOKING, THERE IS NOW STRONG EVIDENCE SUGGESTING THAT PREDISPOSITION TO THE DEVELOPMENT OF METABOLIC SYNDROME BEGINS IN UTERO. FIRST POSITED BY HALES AND BARKER IN 1992, THE "THRIFTY PHENOTYPE" HYPOTHESIS PROPOSES THAT SUSCEPTIBILITY TO ADULT CHRONIC DISEASES CAN OCCUR IN RESPONSE TO EXPOSURES IN THE PRENATAL AND PERINATAL PERIODS. THIS HYPOTHESIS HAS BEEN CONTINUALLY SUPPORTED BY EPIDEMIOLOGIC STUDIES AND STUDIES INVOLVING ANIMAL MODELS. IN THIS REVIEW, WE DESCRIBE THE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES THAT OCCUR IN RESPONSE TO ADVERSE INTRAUTERINE ENVIRONMENTS INCLUDING PRENATAL AND POSTNATAL DIET, MATERNAL OBESITY, AND PREGNANCY COMPLICATIONS. GIVEN THE INCREASING PREVALENCE OF METABOLIC SYNDROME IN BOTH THE DEVELOPED AND DEVELOPING WORLDS, A GREATER UNDERSTANDING AND APPRECIATION FOR THE ROLE OF THE INTRAUTERINE ENVIRONMENT IN ADULT CHRONIC DISEASE ETIOLOGY IS IMPERATIVE. 2015 13 931 25 CHRONIC KIDNEY DISEASE IN CHILDREN AND THE ROLE OF EPIGENETICS: FUTURE THERAPEUTIC TRAJECTORIES. GLOBAL DIFFERENCES IN THE OBSERVED CAUSES OF CHRONIC KIDNEY DISEASE (CKD) IN CHILDREN ARE WELL DOCUMENTED AND ARE ATTRIBUTED TO DISSIMILARITIES IN CLIME, RACE, HEREDITARY, AND ANCESTRY. THUS, FAMILIAL CLUSTERING AND DISPARITIES IN CKD PREVALENCE RATES ACROSS ETHNIC AND RACIAL GROUPS INDICATE THAT THE PROGRESSION OF RENAL DISEASE HAS A STRONG GENETIC COMPONENT. MAMMALIAN STUDIES HAVE DEMONSTRATED A FEASIBLE NEXUS BETWEEN NUTRITION AND NON-GENETIC EXPOSURE (AROUND THE TIME OF CONCEPTION AND IN EPIGENETIC CHANGES) IN THE EXPRESSION OF MAJOR GENES IDENTIFIED IN RENAL ORGANOGENESIS. THE MAJOR CONSEQUENCE IS A REDUCTION IN THE NUMBER OF NEPHRONS, WITH SUBSEQUENT PREDISPOSITION TO HYPERTENSION AND CKD. IDENTIFYING THESE EPIGENETIC CHANGES IS CRUCIAL (DUE TO THEIR POTENTIALLY REVERSIBLE NATURE), AS THEY MAY SERVE AS FUTURE THERAPEUTIC TARGETS TO PREVENT KIDNEY FIBROSIS AND CKD. DESPITE PROGRESS IN THE FIELD OF EPIGENETICS IN ONCOLOGY, RESEARCH IN OTHER SUBSPECIALTIES OF MEDICINE IS LARGELY EXPERIMENTAL WITH FEW EXISTING STUDIES REGARDING THE CLINICAL IMPLICATION OF EPIGENETICS IN RENAL DISEASE. THERAPEUTIC TRAJECTORIES FOR CKD IN CHILDREN BASED ON THE INFLUENCE OF EPIGENETICS MAY EVENTUALLY REVOLUTIONIZE THE MANAGEMENT OF THIS DISEASE. THE AIM OF THE CURRENT NARRATIVE REVIEW IS TO APPRAISE THE ROLE OF EPIGENETICS IN CKD, AND HIGHLIGHT THE POTENTIAL FUTURE THERAPEUTIC PATHWAYS. 2016 14 2579 27 EPIGENETICS OF KIDNEY DISEASE. DNA METHYLATION AND HISTONE MODIFICATIONS DETERMINE RENAL PROGRAMMING AND THE DEVELOPMENT AND PROGRESSION OF RENAL DISEASE. THE IDENTIFICATION OF THE WAY IN WHICH THE RENAL CELL EPIGENOME IS ALTERED BY ENVIRONMENTAL MODIFIERS DRIVING THE ONSET AND PROGRESSION OF RENAL DISEASES HAS EXTENDED OUR UNDERSTANDING OF THE PATHOPHYSIOLOGY OF KIDNEY DISEASE PROGRESSION. IN THIS REVIEW, WE FOCUS ON CURRENT KNOWLEDGE CONCERNING THE IMPLICATIONS OF EPIGENETIC MODIFICATIONS DURING RENAL DISEASE FROM EARLY DEVELOPMENT TO CHRONIC KIDNEY DISEASE PROGRESSION INCLUDING RENAL FIBROSIS, DIABETIC NEPHROPATHY AND THE TRANSLATIONAL POTENTIAL OF IDENTIFYING NEW BIOMARKERS AND TREATMENTS FOR THE PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE AND END-STAGE KIDNEY DISEASE. 2017 15 49 26 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 16 6001 27 THE ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE TRANSITION: A POTENTIAL OPPORTUNITY TO IMPROVE CARE IN ACUTE KIDNEY INJURY. RECENT CONTROLLED TRIALS, EPIDEMIOLOGICAL ANALYSES AND BASIC RESEARCH STUDIES OFFER A COMPREHENSIVE VIEW OF THE SHORT AND LONG-TERM CLINICAL REPERCUSSION OF DE NOVO ACUTE KIDNEY INJURY OR AKI. WHILE MOST POST-AKI PATIENTS RECOVER THEIR BASELINE RENAL FUNCTION, A SIGNIFICANT NUMBER, APPROXIMATELY ~20% OF THOSE AFFECTED, WILL GO ON TO DEVELOP LONG TERM ILLNESS CHARACTERIZED BY AN INCREASE IN LATE STAGE CKD, CARDIOVASCULAR COMPLICATIONS, AND INCREASED DEATH RATES. WHEN AKI OCCURS IN HOSPITALIZED PATIENTS, SELECTED DEMOGRAPHIC AND LABORATORY RESULTS CAN BE INCORPORATED INTO RISK CALCULATORS THAT IDENTIFY THOSE AT HIGHER RISK FOR LONG-TERM COMPLICATIONS. THIS REVIEW TOUCHES ON SOME OF THE SALIENT EPIDEMIOLOGICAL STUDIES OF THE AKI TO CKD TRANSITION. IT ALSO FOCUSES ON CERTAIN RECENT ADVANCEMENTS IN OUR UNDERSTANDING OF THE BIOLOGICAL AND FUNCTIONAL IMPACT OF AKI ON THE RENAL TUBULE REPAIR MECHANISM, AS WELL AS THE IMPORTANT ROLE THAT GENETIC, EPIGENETIC, BIOCHEMICAL AND INFLAMMATORY EVENTS, SEEMINGLY BENEFICIAL TO THE RE-ESTABLISHMENT OF NORMAL RENAL FUNCTION, CAN BE OFFSET BY MEDIATORS OF PROGRESSIVE FIBROSIS AND IRREVERSIBLE STRUCTURAL CHANGES. CHARACTERIZATION OF BASIC PROCESSES THAT MEDIATE THE AKI TO CKD TRANSITION REVEALS PROMISING PHARMACOLOGICAL AND BIOLOGICAL AGENTS THAT HOPEFULLY WILL ONE DAY BE USED IN THE EARLY STAGES OF AKI TO PREVENT ITS DEADLY CONSEQUENCES. 2016 17 1241 31 CURRENT AND FUTURE NUTRITIONAL STRATEGIES TO MODULATE INFLAMMATORY DYNAMICS IN METABOLIC DISORDERS. OBESITY, TYPE 2 DIABETES, AND OTHER METABOLIC DISORDERS HAVE A LARGE IMPACT ON GLOBAL HEALTH, ESPECIALLY IN WESTERN COUNTRIES. AN IMPORTANT HALLMARK OF METABOLIC DISORDERS IS CHRONIC LOW-GRADE INFLAMMATION. A KEY PLAYER IN CHRONIC LOW-GRADE INFLAMMATION IS DYSMETABOLISM, WHICH IS DEFINED AS THE INABILITY TO KEEP HOMEOSTASIS RESULTING IN LOSS OF LIPID CONTROL, OXIDATIVE STRESS, INFLAMMATION, AND INSULIN RESISTANCE. ALTHOUGH OFTEN NOT YET DETECTABLE IN THE CIRCULATION, CHRONIC LOW-GRADE INFLAMMATION CAN BE PRESENT IN ONE OR MULTIPLE ORGANS. THE RESPONSE TO A METABOLIC CHALLENGE CONTAINING LIPIDS MAY MAGNIFY DYSFUNCTIONALITIES AT THE TISSUE LEVEL, CAUSING AN OVERFLOW OF INFLAMMATORY MARKERS INTO THE CIRCULATION AND HENCE ALLOW DETECTION OF EARLY LOW-GRADE INFLAMMATION. HERE, WE SUMMARIZE THE EVIDENCE OF SUCCESSFUL APPLICATION OF METABOLIC CHALLENGE TESTS IN TYPE 2 DIABETES, METABOLIC SYNDROME, OBESITY, AND UNHEALTHY AGING. WE ALSO REVIEW HOW METABOLIC CHALLENGE TESTS HAVE BEEN SUCCESSFULLY APPLIED TO EVALUATE NUTRITIONAL INTERVENTION EFFECTS, INCLUDING AN "ANTI-INFLAMMATORY" MIXTURE, DARK CHOCOLATE, WHOLE GRAIN WHEAT AND OVERFEEDING. ADDITIONALLY, WE ELABORATE ON FUTURE STRATEGIES TO (RE)GAIN INFLAMMATORY FLEXIBILITY. THROUGH EPIGENETIC AND METABOLIC REGULATION, THE INFLAMMATORY RESPONSE MAY BE TRAINED BY REGULAR MILD AND METABOLIC TRIGGERS, WHICH CAN BE UNDERSTOOD FROM THE PERSPECTIVE OF TRAINED IMMUNITY, HORMESIS AND PRO-RESOLUTION. NEW STRATEGIES TO OPTIMIZE DYNAMICS OF INFLAMMATION MAY BECOME AVAILABLE. 2019 18 650 21 BISPHENOL A AND HUMAN CHRONIC DISEASES: CURRENT EVIDENCES, POSSIBLE MECHANISMS, AND FUTURE PERSPECTIVES. BISPHENOL-A (BPA) IS ONE OF THE HIGHEST VOLUME CHEMICALS PRODUCED WORLDWIDE, WITH OVER 6BILLION POUNDS PRODUCED AND OVER 100T RELEASED INTO THE ATMOSPHERE EACH YEAR. RECENT EXTENSIVE LITERATURE HAS RAISED CONCERNS ABOUT ITS POSSIBLE IMPLICATION IN THE ETIOLOGY OF SOME HUMAN CHRONIC DISEASES SUCH AS DIABETES, OBESITY, REPRODUCTIVE DISORDERS, CARDIOVASCULAR DISEASES, BIRTH DEFECTS, CHRONIC RESPIRATORY AND KIDNEY DISEASES AND BREAST CANCER. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCES ON THE RELATIONSHIP BETWEEN BPA EXPOSURE AND HUMAN CHRONIC DISEASES AND WE DISCUSS ITS EVENTUAL MECHANISMS OF ACTION, ESPECIALLY GENETIC, EPIGENETIC AND ENDOCRINE DISRUPTION MECHANISMS WITH THE POSSIBLE INVOLVEMENT OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL SIGNALING. 2014 19 4972 28 PATHOPHYSIOLOGICAL BASIS FOR COMPROMISED HEALTH BEYOND GENERATIONS: ROLE OF MATERNAL HIGH-FAT DIET AND LOW-GRADE CHRONIC INFLAMMATION. EARLY EXPOSURE TO A FAT-ENRICHED DIET PROGRAMS THE DEVELOPMENTAL PROFILE AND THUS IS ASSOCIATED WITH DISEASE SUSCEPTIBILITY IN SUBSEQUENT GENERATIONS. CHRONIC LOW-GRADE INFLAMMATION, RESULTING FROM MATERNAL HIGH-FAT DIET, IS ACTIVATED IN THE FETAL ENVIRONMENT AND IN MANY ORGANS OF OFFSPRING, INCLUDING PLACENTA, ADIPOSE, LIVER, VASCULAR SYSTEM AND BRAIN. THE PREVALENCE OF AN INFLAMMATORY RESPONSE IS HIGHLY ASSOCIATED WITH OBESITY INCIDENCE, CARDIOVASCULAR DISEASES, NONALCOHOLIC FATTY LIVER DISEASE AND BRAIN DAMAGE. SUBSTANTIAL STUDIES USING HIGH-FAT MODEL HAVE CONSISTENTLY DEMONSTRATED THE INCIDENCE OF SUCH INFLAMMATORY REACTIONS; HOWEVER, THE POTENTIAL CONTRIBUTION OF ACTIVE INFLAMMATION TOWARD THE PHYSIOLOGICAL OUTCOMES AND DEVELOPMENTAL DISEASES IS NEITHER DISCUSSED IN DEPTH NOR SYSTEMICALLY INTEGRATED. THEREFORE, WE AIM TO SUMMARIZE THE CURRENT FINDINGS IN REGARDS TO HOW A MATERNAL HIGH-FAT DIET INFLUENCES THE INFLAMMATORY STATUS, AND PROBABLE PATHOGENIC EFFECTS ON THE OFFSPRING. MORE IMPORTANTLY, SINCE LIMITED RESEARCH HAS BEEN CONDUCTED TO REVEAL THE EPIGENETIC REGULATION OF THESE INFLAMMATORY MARKERS BY MATERNAL HIGH-FAT DIET, WE SINCERELY HOPE THAT OUR REVIEW WILL NOT ONLY OUTLINE THE PATHOPHYSIOLOGICAL RELEVANCE OF INFLAMMATION BUT ALSO IDENTIFY A FUTURE DIRECTION FOR MECHANISTIC INVESTIGATION AND CLINICAL APPLICATION. 2015 20 4662 26 NEW DEVELOPMENTS IN THE PATHOGENESIS OF OBESITY-INDUCED HYPERTENSION. OBESITY IS A DISORDER THAT DEVELOPS FROM THE INTERACTION BETWEEN GENOTYPE AND ENVIRONMENT INVOLVING SOCIAL, BEHAVIORAL, CULTURAL, AND PHYSIOLOGICAL FACTORS. OBESITY INCREASES THE RISK FOR TYPE 2 DIABETES MELLITUS, HYPERTENSION, CARDIOVASCULAR DISEASE, CANCER, MUSCULOSKELETAL DISORDERS, CHRONIC KIDNEY AND PULMONARY DISEASE. ALTHOUGH OBESITY IS CLEARLY ASSOCIATED WITH AN INCREASED PREVALENCE OF HYPERTENSION, MANY OBESE INDIVIDUALS MAY NOT DEVELOP HYPERTENSION. PROTECTING FACTORS MAY EXIST AND IT IS IMPORTANT TO UNDERSTAND WHY OBESITY IS NOT ALWAYS RELATED TO HYPERTENSION. THE AIM OF THIS REVIEW IS TO HIGHLIGHT THE KNOWLEDGE GAP FOR THE ASSOCIATION BETWEEN OBESITY, HYPERTENSION, AND POTENTIAL GENETIC AND RACIAL DIFFERENCES OR ENVIRONMENTAL FACTORS THAT MAY PROTECT OBESE PATIENTS AGAINST THE DEVELOPMENT OF HYPERTENSION AND OTHER CO-MORBIDITIES. SPECIFIC MUTATIONS IN THE LEPTIN AND THE MELANINOCORTIN RECEPTOR GENES IN ANIMAL MODELS OF OBESITY WITHOUT HYPERTENSION, THE ACTIONS OF ALPHA-MELANOCYTE STIMULATING HORMONE, AND SNS ACTIVITY IN OBESITY-RELATED HYPERTENSION MAY PROMOTE RECOGNITION OF PROTECTIVE AND PROMOTING FACTORS FOR HYPERTENSION IN OBESITY. FURTHERMORE, GENE-ENVIRONMENT INTERACTIONS MAY HAVE THE POTENTIAL TO MODIFY GENE EXPRESSION AND EPIGENETIC MECHANISMS COULD ALSO CONTRIBUTE TO THE HERITABILITY OF OBESITY-INDUCED HYPERTENSION. FINALLY, DIFFERENCES IN NUTRITION, GUT MICROBIOTA, EXPOSURE TO SUN LIGHT AND EXERCISE MAY PLAY AN IMPORTANT ROLE IN THE PRESENCE OR ABSENCE OF HYPERTENSION IN OBESITY. 2015