1 618 137 BIOBEHAVIORAL MECHANISMS ASSOCIATED WITH NONHEALING WOUNDS AND PSYCHONEUROLOGIC SYMPTOMS (PAIN, COGNITIVE DYSFUNCTION, FATIGUE, DEPRESSION, AND ANXIETY) IN OLDER INDIVIDUALS WITH CHRONIC VENOUS LEG ULCERS. THE PREVALENCE AND INCIDENCE OF CHRONIC VENOUS LEG ULCERS (CVLUS) ARE INCREASING WORLDWIDE, AS ARE THE ASSOCIATED FINANCIAL COSTS. ALTHOUGH IT HAS LONG BEEN KNOWN THAT THEIR UNDERLYING ETIOLOGY IS VENOUS INSUFFICIENCY, THE MOLECULAR ASPECTS OF HEALING VERSUS NONHEALING, AS WELL AS THE PSYCHONEUROLOGIC SYMPTOMS (PNS; PAIN, COGNITIVE DYSFUNCTION, FATIGUE, DEPRESSION, AND ANXIETY) ASSOCIATED WITH CVLUS REMAIN UNDERSTUDIED. IN THIS BIOBEHAVIORALLY FOCUSED REVIEW, WE AIM TO ELUCIDATE THE COMPLEX MECHANISMS THAT LINK THE BIOLOGICAL AND MOLECULAR ASPECTS OF CLVUS WITH THEIR PNS. INNOVATIONS IN "OMICS" RESEARCH HAVE INCREASED OUR UNDERSTANDING OF IMPORTANT WOUND MICROENVIRONMENTAL FACTORS (E.G., INFLAMMATION, MICROBIAL PATHOGENIC BIOFILM, EPIGENETIC PROCESSES) THAT MAY ADVERSELY ALTER THE WOUND BED'S MOLECULAR MILIEU SO THAT MICROBES EVADE IMMUNE DETECTION. ALTHOUGH THESE MOLECULAR FACTORS ARE NOT SINGULARLY RESPONSIBLE FOR WOUND HEALING, THEY ARE MAJOR COMPONENTS OF WOUND DEVELOPMENT, NONHEALING, AND PNS THAT, UNTIL NOW, HAVE NOT BEEN AMENABLE TO SYSTEMATIC STUDY, ESPECIALLY OVER TIME. FURTHER, THIS REVIEW EXPLORES OUR CURRENT UNDERSTANDING OF THE MOLECULAR MECHANISMS BY WHICH THE IMMUNE ACTIVATION THAT CONTRIBUTES TO THE DEVELOPMENT AND PERSISTENCE OF CVLUS ALSO LEADS TO THE DEVELOPMENT, PERSISTENCE, AND SEVERITY OF WOUND-RELATED PNS. WE ALSO MAKE RECOMMENDATIONS FOR FUTURE RESEARCH THAT WILL EXPAND THE FIELD OF BIOBEHAVIORAL WOUND SCIENCE. BIOBEHAVIORAL RESEARCH THAT FOCUSES ON THE INTERRELATED MECHANISMS OF PNS WILL LEAD TO SYMPTOM-MANAGEMENT INTERVENTIONS THAT IMPROVE QUALITY OF LIFE FOR THE POPULATION BURDENED BY CVLUS. 2019 2 2000 31 EPIGENETIC AND NON-CODING REGULATION OF ALCOHOL ABUSE AND ADDICTION. ALCOHOL USE DISORDER IS A CHRONIC DEBILITATED CONDITION ADVERSELY AFFECTING THE LIVES OF MILLIONS OF INDIVIDUALS THROUGHOUT THE MODERN WORLD. INDIVIDUALS SUFFERING FROM AN ALCOHOL USE DISORDER DIAGNOSIS FREQUENTLY HAVE SERIOUS COOCCURRING CONDITIONS, WHICH OFTEN FURTHER EXACERBATES PROBLEMATIC DRINKING BEHAVIOR. COMPREHENDING THE BIOCHEMICAL PROCESSES UNDERLYING THE PROGRESSION AND PERPETUATION OF DISEASE IS ESSENTIAL FOR MITIGATING MALADAPTIVE BEHAVIOR IN ORDER TO RESTORE BOTH PHYSIOLOGICAL AND PSYCHOLOGICAL HEALTH. THE RANGE OF CELLULAR AND BIOLOGICAL SYSTEMS CONTRIBUTING TO, AND AFFECTED BY, ALCOHOL USE DISORDER AND OTHER COMORBID DISORDERS NECESSITATES A FUNDAMENTAL GRASP OF INTRICATE FUNCTIONAL RELATIONSHIPS THAT GOVERN MOLECULAR BIOLOGY. EPIGENETIC FACTORS ARE RECOGNIZED AS ESSENTIAL MEDIATORS OF CELLULAR BEHAVIOR, ORCHESTRATING A SYMPHONY OF GENE EXPRESSION CHANGES WITHIN MULTICELLULAR ENVIRONMENTS THAT ARE ULTIMATELY RESPONSIBLE FOR DIRECTING HUMAN BEHAVIOR. UNDERSTANDING THE EPIGENETIC AND TRANSCRIPTIONAL REGULATORY MECHANISMS INVOLVED IN THE PATHOGENESIS OF DISEASE IS IMPORTANT FOR IMPROVING AVAILABLE PHARMACOTHERAPIES AND REDUCING THE INCIDENCE OF ALCOHOL ABUSE AND COOCCURRING CONDITIONS. 2021 3 5810 24 STRESS & SLEEP: A RELATIONSHIP LASTING A LIFETIME. STRESS IS AN ADAPTATIVE RESPONSE AIMED AT RESTORING BODY HOMEOSTASIS. THE CLASSICAL NEUROENDOCRINE STRESS RESPONSE INVOLVING THE ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS MODULATES MANY PHYSIOLOGICAL ASPECTS, SUCH AS THE WAKE-SLEEP CYCLE. IN THE PRESENT REVIEW, WE WILL FIRST REPORT A SERIES OF HUMAN AND RODENT STUDIES SHOWING THAT EACH ACTOR OF THE HPA AXIS HAS THE POTENTIAL TO INTERFERE WITH SLEEP HOMEOSTASIS AND, THEN, WE WILL HIGHLIGHT HOW ACUTE OR CHRONIC STRESS DIFFERENTLY MODULATES THE WAKE-SLEEP CYCLE. MOREOVER, WE WILL PRESENT NEW AND INTERESTING STUDIES DEALING WITH THE RELATIONSHIP BETWEEN SLEEP AND STRESS ON A DIFFERENT (LONGER) TIME SCALE. PARTICULARLY, WE WILL DISCUSS HOW THE EXPOSURE TO PERINATAL STRESS, PROBABLY THROUGH EPIGENETIC MODULATIONS, IS SUFFICIENT TO CAUSE PERSISTENT SLEEP DERANGEMENTS DURING ADULT LIFE. IN LIGHT OF THIS EVIDENCE, THE MAIN MESSAGE OF THE PRESENT REVIEW IS THAT THE COMPLEX RELATIONSHIP BETWEEN SLEEP AND STRESS CHANGES DRAMATICALLY ON THE BASIS OF THE TIME SCALE CONSIDERED AND, CONSEQUENTLY, "TIME" SHOULD BE CONSIDERED AS A CRITICAL FACTOR WHEN FACING THIS TOPIC. 2020 4 6853 32 [NEUROBIOLOGY OF EARLY LIFE TRAUMATIC STRESS AND TRAUMA: PROLONGED NEUROENDOCRINE DYSREGULATION AS A NEURODEVELOPMENTAL RISK FACTOR]. EARLY LIFE STRESSORS DISPLAY A HIGH UNIVERSAL PREVALENCE AND CONSTITUTE A MAJOR PUBLIC HEALTH PROBLEM WITH TWO THIRDS OF YOUTH BEING EXPOSED TO POTENTIALLY TRAUMATIC EXPERIENCES BY THE AGE OF 17. TRAUMATIC STRESS EXPOSURE DURING CRITICAL PERIODS OF DEVELOPMENT MAY HAVE ESSENTIAL AND LONG-LASTING EFFECTS ON THE PHYSICAL AND MENTAL HEALTH OF INDIVIDUALS AND REPRESENTS A DEVELOPMENTAL RISK FACTOR MEDIATING RISK FOR DISEASE. EARLY-LIFE STRESS (ELS) AND CHILDHOOD TRAUMA (CT) CAN BOTH HAVE AN IMPACT ON SENSITIVE NEURONAL BRAIN NETWORKS INVOLVED IN STRESS REACTIONS, AND COULD EXERT A PROGRAMMING EFFECT ON GLUCOCORTICOID SIGNALING LEADING TO CHRONIC HYPER- OR HYPO-ACTIVATION OF THE STRESS SYSTEM. IN ADDITION, ALTERATIONS IN EMOTIONAL AND AUTONOMIC REACTIVITY, CIRCADIAN RHYTHM DISRUPTION, FUNCTIONAL AND STRUCTURAL CHANGES IN THE BRAIN, AS WELL AS IMMUNE AND METABOLIC DYSREGULATION HAVE BEEN LATELY IDENTIFIED AS IMPORTANT RISK FACTORS FOR A CHRONICALLY IMPAIRED HOMEOSTATIC BALANCE AFTER ELS/CT. FURTHERMORE, HUMAN GENETIC BACKGROUND AND EPIGENETIC MODIFICATIONS THROUGH STRESS-RELATED GENE EXPRESSION COULD INTERACT WITH THESE ALTERATIONS AND EXPLAIN INTER-INDIVIDUAL VARIATION IN VULNERABILITY OR RESILIENCE TO STRESS. THIS NARRATIVE REVIEW PRESENTS RELEVANT EVIDENCE FROM MAINLY HUMAN RESEARCH ON THE MOST ACKNOWLEDGED NEUROBIOLOGICAL ALLOSTATIC PATHWAYS EXERTING ENDURING ADVERSE EFFECTS OF ELS/CT EVEN DECADES LATER. FUTURE STUDIES SHOULD PROSPECTIVELY INVESTIGATE POTENTIAL CONFOUNDERS, THEIR TEMPORAL SEQUENCE AND COMBINED EFFECTS AT THE BIOLOGICAL LEVEL, WHILE CONSIDERING THE POTENTIALLY DELAYED TIME-FRAME FOR THE EXPRESSION OF THEIR EFFECTS. FINALLY, SCREENING STRATEGIES FOR ELS/CT AND TRAUMA NEED TO BE IMPROVED. INFORMATION ABOUT ELS/CT HISTORY AND THE NUMBER OF ADVERSE EXPERIENCES COULD HELP TO BETTER IDENTIFY THE INDIVIDUAL RISK FOR DISEASE DEVELOPMENT, PREDICT INDIVIDUAL TREATMENT RESPONSE AND DESIGN PREVENTION STRATEGIES TO REDUCE THE NEGATIVE EFFECTS OF ELS/CT. 2023 5 2528 31 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 6 49 27 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 7 627 32 BIOLOGICAL AGING PROCESSES UNDERLYING COGNITIVE DECLINE AND NEURODEGENERATIVE DISEASE. ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) ARE AMONG THE TOP CONTRIBUTORS TO DISABILITY AND MORTALITY IN LATER LIFE. AS WITH MANY CHRONIC CONDITIONS, AGING IS THE SINGLE MOST INFLUENTIAL FACTOR IN THE DEVELOPMENT OF ADRD. EVEN AMONG OLDER ADULTS WHO REMAIN FREE OF DEMENTIA THROUGHOUT THEIR LIVES, COGNITIVE DECLINE AND NEURODEGENERATIVE CHANGES ARE APPRECIABLE WITH ADVANCING AGE, SUGGESTING SHARED PATHOPHYSIOLOGICAL MECHANISMS. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF CHANGES IN COGNITION, BRAIN MORPHOLOGY, AND NEUROPATHOLOGICAL PROTEIN ACCUMULATION ACROSS THE LIFESPAN IN HUMANS, WITH COMPLEMENTARY AND MECHANISTIC EVIDENCE FROM ANIMAL MODELS. NEXT, WE HIGHLIGHT SELECTED AGING PROCESSES THAT ARE DIFFERENTIALLY REGULATED IN NEURODEGENERATIVE DISEASE, INCLUDING ABERRANT AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, EPIGENETIC CHANGES, CEREBROVASCULAR DYSFUNCTION, INFLAMMATION, AND LIPID DYSREGULATION. WE SUMMARIZE RESEARCH ACROSS CLINICAL AND TRANSLATIONAL STUDIES TO LINK BIOLOGICAL AGING PROCESSES TO UNDERLYING ADRD PATHOGENESIS. TARGETING FUNDAMENTAL PROCESSES UNDERLYING BIOLOGICAL AGING MAY REPRESENT A YET RELATIVELY UNEXPLORED AVENUE TO ATTENUATE BOTH AGE-RELATED COGNITIVE DECLINE AND ADRD. COLLABORATION ACROSS THE FIELDS OF GEROSCIENCE AND NEUROSCIENCE, COUPLED WITH THE DEVELOPMENT OF NEW TRANSLATIONAL ANIMAL MODELS THAT MORE CLOSELY ALIGN WITH HUMAN DISEASE PROCESSES, IS NECESSARY TO ADVANCE NOVEL THERAPEUTIC DISCOVERY IN THIS REALM. 2022 8 705 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 9 2586 29 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 10 421 28 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 11 2136 37 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 12 4495 33 MORE GAIN, LESS PAIN: HOW RESISTANCE TRAINING AFFECTS IMMUNE SYSTEM FUNCTIONING IN MULTIPLE SCLEROSIS PATIENTS: A REVIEW. MULTIPLE SCLEROSIS (MS) IS CHARACTERIZED BY A COMPLEX ETIOLOGY THAT IS MIRRORED BY THE PERPLEXING AND INCONSISTENT TREATMENT RESPONSES OBSERVED ACROSS DIFFERENT PATIENTS. ALTHOUGH EPIGENETIC RESEARCH HAS GARNERED RIGHTFUL INTEREST IN ITS EFFORTS TOWARDS DEMYSTIFYING AND UNDERSTANDING ABERRANT RESPONSES TO TREATMENT, THE INTERIM UNDOUBTEDLY REQUIRES ALTERNATIVE NON-PHARMACOLOGICAL APPROACHES TOWARDS ATTAINING MORE EFFECTIVE MANAGEMENT STRATEGIES. OF PARTICULAR INTEREST IN THIS REVIEW IS RESISTANCE TRAINING (RT) AS A NON-PHARMACOLOGICAL EXERCISE-BASED INTERVENTIONAL STRATEGY AND ITS POTENTIAL ROLE AS A DISEASE-MODIFYING TOOL. RT HAS BEEN REPORTED ACROSS LITERATURE TO POSITIVELY INFLUENCE NUMEROUS ASPECTS IN THE QUALITY OF LIFE (QOL) AND FUNCTIONAL CAPACITY OF MS PATIENTS, AND ONE OF THE ATTRIBUTES OF THESE BENEFITS MAY BE A SHIFT IN THE IMMUNE SYSTEM OF THESE INDIVIDUALS. RT HAS ALSO BEEN PROVEN TO AFFECT DIFFERENT IMMUNE SYSTEM KEY PLAYERS ASSOCIATED WITH MS PATHOLOGY. ULTIMATELY, THIS BRIEF REVIEW AIMS TO PROVIDE A POTENTIAL YET CRUCIAL LINK BETWEEN RT, ALTERATIONS IN THE EXPRESSION PROFILE OF THE IMMUNE SYSTEM, AND FINALLY AN IMMINENT IMPROVEMENT IN THE OVERALL WELL-BEING AND QOL OF MS PATIENTS, SUGGESTING THAT UTILIZING RT AS AN INTERVENTIONAL EXERCISE MODALITY MAY BE AN EFFECTIVE STRATEGY THAT WOULD AID IN MANAGING SUCH A COMPLEX AND DEBILITATING DISEASE. 2023 13 4399 28 MODULATION OF GENOMIC AND POSTGENOMIC ALTERATIONS IN NONCANCER DISEASES AND CRITICAL PERIODS OF LIFE. GENOMIC AND POSTGENOMIC CHANGES ARE EXTENSIVELY INVESTIGATED IN CANCER RESEARCH. SIMILAR ALTERATIONS, AFFECTING GENOME, TRANSCRIPTOME, MIRNOME AND/OR PROTEOME END-POINTS, HAVE BEEN DETECTED IN A VARIETY OF OTHER CHRONIC DEGENERATIVE DISEASES, SUCH AS ATHEROSCLEROSIS, DEGENERATIVE HEART DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASES, NEUROLOGICAL DISORDERS, EYE DISEASES, DIABETES, METABOLIC SYNDROME, SKIN AGEING AND ALOPECIA. NO GENERALIZATION CAN BE MADE DUE TO THE MYRIAD OF DIVERSE CLINICAL ENTITIES CLASSIFIED AS CHRONIC DEGENERATIVE DISEASES. MOREOVER, THE DETECTION OF MOLECULAR CHANGES DOES NOT AUTOMATICALLY IMPLY THEIR CAUSAL ROLE. NEVERTHELESS, COMMON MECHANISMS, SUCH AS DNA DAMAGE, EPIGENETIC ALTERATIONS, OXIDATIVE STRESS, AND CHRONIC INFLAMMATION, IN ADDITION TO GENETIC PREDISPOSITION, ARE OFTEN INVOLVED IN NONCANCER DISEASES. WE DEBATE HERE IN MORE DETAIL THE SUBJECTS OF CARDIOVASCULAR DISEASES AND OF SKIN DISEASES. MOREOVER, WE DISCUSS OUR EXPERIMENTAL STUDIES SUGGESTING THAT GENOMIC AND POSTGENOMIC CHANGES DO ALSO OCCUR DURING CRITICAL PERIODS OF LIFE, INCLUDING THE PRENATAL LIFE, THE PERINATAL PERIOD, AND AGEING. IN ADDITION, WE COMMENT ON THE FINDING THAT STEM-DERIVED CELLS ARE MORE SUSCEPTIBLE TO MOLECULAR DAMAGE THAN MORE DIFFERENTIATED CELLS. ALL THESE DATA ARE VIEWED IN THE PERSPECTIVE OF PREVENTIVE MEDICINE. IN FACT, THERE IS EVIDENCE THAT THE GENOMIC AND POSTGENOMIC ALTERATIONS OCCURRING NOT ONLY IN SEVERAL PATHOLOGICAL CONDITIONS BUT ALSO IN PARAPHYSIOLOGICAL SITUATIONS THAT AFFECT CRITICAL PERIODS OF LIFE CAN BE MODULATED BY MEANS OF DIETARY AND PHARMACOLOGICAL AGENTS. THE DISCOVERY THAT CHEMOPREVENTIVE AGENTS ARE ALSO ABLE TO ATTENUATE NUCLEOTIDE DAMAGE IN STEM-DERIVED CELLS WARRANTS FURTHER STUDIES IN VIEW OF POSSIBLE CLINICAL APPLICATIONS. 2009 14 6459 26 TIME TO CHANGE FROM A SIMPLE LINEAR MODEL TO A COMPLEX SYSTEMS MODEL. A SIMPLE LINEAR MODEL TO TEST THE HYPOTHESIS BASED ON ONE-ON-ONE RELATIONSHIP HAS BEEN USED TO FIND THE CAUSATIVE FACTORS OF DISEASES. HOWEVER, WE NOW KNOW THAT NOT JUST ONE, BUT MANY FACTORS FROM DIFFERENT SYSTEMS SUCH AS CHEMICAL EXPOSURE, GENES, EPIGENETIC CHANGES, AND PROTEINS ARE INVOLVED IN THE PATHOGENESIS OF CHRONIC DISEASES SUCH AS DIABETES MELLITUS. SO, WITH AVAILABILITY OF MODERN TECHNOLOGIES TO UNDERSTAND THE INTRICATE NATURE OF RELATIONS AMONG COMPLEX SYSTEMS, WE NEED TO MOVE FORWARD TO THE FUTURE BY TAKING COMPLEX SYSTEMS MODEL. 2016 15 2049 19 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 16 1364 39 DEVELOPMENTAL NEUROENDOCRINOLOGY OF EARLY-LIFE STRESS: IMPACT ON CHILD DEVELOPMENT AND BEHAVIOR. OUR INTERNAL BALANCE, OR HOMEOSTASIS, IS THREATENED OR PERCEIVED AS THREATENED BY STRESSFUL STIMULI, THE STRESSORS. THE STRESS SYSTEM IS A HIGHLY CONSERVED SYSTEM THAT ADJUSTS HOMEOSTASIS TO THE RESTING STATE. THROUGH THE CONCURRENT ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND THE LOCUS COERULEUS/NOREPINEPHRINE-AUTONOMIC NERVOUS SYSTEMS, THE STRESS SYSTEM PROVIDES THE APPROPRIATE PHYSICAL AND BEHAVIORAL RESPONSES, COLLECTIVELY TERMED AS "STRESS RESPONSE", TO RESTORE HOMEOSTASIS. IF THE STRESS RESPONSE IS PROLONGED, EXCESSIVE OR EVEN INADEQUATE, SEVERAL ACUTE OR CHRONIC STRESS-RELATED PATHOLOGIC CONDITIONS MAY DEVELOP IN CHILDHOOD, ADOLESCENCE AND ADULT LIFE. ON THE OTHER HAND, EARLY-LIFE EXPOSURE TO STRESSORS HAS BEEN RECOGNIZED AS A MAJOR CONTRIBUTING FACTOR UNDERLYING THE PATHOGENESIS OF NON-COMMUNICABLE DISORDERS, INCLUDING NEURODEVELOPMENTAL DISORDERS. ACCUMULATING EVIDENCE SUGGESTS THAT EARLY-LIFE STRESS HAS BEEN ASSOCIATED WITH AN INCREASED RISK FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER AND AUTISM SPECTRUM DISORDER IN THE OFFSPRING, ALTHOUGH FINDINGS ARE STILL CONTROVERSIAL. NEVERTHELESS, AT THE MOLECULAR LEVEL, EARLY-LIFE STRESSORS ALTER THE CHEMICAL STRUCTURE OF CYTOSINES LOCAT- ED IN THE REGULATORY REGIONS OF GENES, MOSTLY THROUGH THE ADDITION OF METHYL GROUPS. THESE EPIGENETIC MODIFICATIONS RESULT IN THE SUPPRESSION OF GENE EXPRESSION WITHOUT CHANGING THE DNA SEQUENCE. IN ADDITION TO DNA METHYLATION, SEVERAL LINES OF EVIDENCE SUPPORT THE ROLE OF NON-CODING RNAS IN THE EVOLVING FIELD OF EPIGENETICS. IN THIS REVIEW ARTICLE, WE PRESENT THE ANATOMICAL AND FUNCTIONAL COMPO- NENTS OF THE STRESS SYSTEM, DISCUSS THE PROPER, IN TERMS OF QUALITY AND QUANTITY, STRESS RESPONSE, AND PROVIDE AN UPDATE ON THE IMPACT OF EARLY-LIFE STRESS ON CHILD DEVELOPMENT AND BEHAVIOR. 2023 17 6350 30 THE ROLE OF EPIGENOMICS IN AQUATIC TOXICOLOGY. OVER THE PAST DECADE, THE FIELD OF MOLECULAR BIOLOGY HAS RAPIDLY INCORPORATED EPIGENETIC STUDIES TO EVALUATE ORGANISM-ENVIRONMENT INTERACTIONS THAT CAN RESULT IN CHRONIC EFFECTS. SUCH RESPONSES ARISE FROM EARLY LIFE STAGE STRESS, THE UTILIZATION OF GENETIC INFORMATION OVER AN INDIVIDUAL'S LIFE TIME, AND TRANSGENERATIONAL INHERITANCE. KNOWLEDGE OF EPIGENETIC MECHANISMS PROVIDES THE POTENTIAL FOR A COMPREHENSIVE EVALUATION OF MULTIGENERATIONAL AND HERITABLE EFFECTS FROM ENVIRONMENTAL STRESSORS, SUCH AS CONTAMINANTS. FOCUSED STUDIES HAVE PROVIDED A GREATER UNDERSTANDING OF HOW MANY RESPONSES TO ENVIRONMENTAL STRESSORS ARE DRIVEN BY EPIGENETIC MODIFIERS. WE DISCUSS THE PROMISE OF EPIGENETICS AND SUGGEST FUTURE RESEARCH DIRECTIONS WITHIN THE FIELD OF AQUATIC TOXICOLOGY, WITH A PARTICULAR FOCUS ON THE POTENTIAL FOR IDENTIFYING KEY HERITABLE MARKS WITH CONSEQUENTIAL IMPACTS AT THE ORGANISM AND POPULATION LEVELS. ENVIRON TOXICOL CHEM 2017;36:2565-2573. (C) 2017 SETAC. 2017 18 28 33 A BIOMIMETIC NATURAL SCIENCES APPROACH TO UNDERSTANDING THE MECHANISMS OF AGEING IN BURDEN OF LIFESTYLE DISEASES. THE WORLDWIDE LANDSCAPE OF AN AGEING POPULATION AND AGE-RELATED DISEASE BRINGS WITH IT HUGE SOCIO-ECONOMIC AND PUBLIC HEALTHCARE CONCERNS ACROSS NATIONS. CORRESPONDINGLY, MONUMENTAL HUMAN AND FINANCIAL RESOURCES HAVE BEEN INVESTED IN BIOMEDICAL RESEARCH, WITH A MISSION TO DECODE THE MECHANISMS OF AGEING AND HOW THESE CONTRIBUTE TO AGE-RELATED DISEASE. MULTIPLE HALLMARKS OF AGEING HAVE BEEN IDENTIFIED THAT ARE COMMON ACROSS TAXA, HIGHLIGHTING THEIR FUNDAMENTAL IMPORTANCE. THESE INCLUDE DYSREGULATED MITOCHONDRIAL METABOLISM AND TELOMERES BIOLOGY, EPIGENETIC MODIFICATIONS, CELL-MATRIX INTERACTIONS, PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, STEM CELL EXHAUSTION, INFLAMMAGEING AND IMMUNO-SENESCENCE. WHILE OUR UNDERSTANDING OF THE MOLECULAR BASIS OF AGEING IS IMPROVING, IT REMAINS A COMPLEX AND MULTIFACTORIAL PROCESS THAT REMAINS TO BE FULLY UNDERSTOOD. A KEY ASPECT OF THE SHORTFALL IN OUR UNDERSTANDING OF THE AGEING PROCESS LIES IN TRANSLATING DATA FROM STANDARD ANIMAL MODELS TO HUMANS. CONSEQUENTLY, WE SUGGEST THAT A 'BIOMIMETIC' AND COMPARATIVE APPROACH, INTEGRATING KNOWLEDGE FROM SPECIES IN THE WILD, AS OPPOSED TO INBRED GENETICALLY HOMOGENOUS LABORATORY ANIMALS, CAN PROVIDE POWERFUL INSIGHTS INTO HUMAN AGEING PROCESSES. HERE WE DISCUSS SOME PARTICULARITIES AND COMPARATIVE PATTERNS AMONG SEVERAL SPECIES FROM THE ANIMAL KINGDOM, ENDOWED WITH LONGEVITY OR SHORT LIFESPANS AND UNIQUE METABOLIC PROFILES THAT COULD BE POTENTIALLY EXPLOITED TO THE UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES. BASED UPON LESSONS FROM NATURE, WE ALSO HIGHLIGHT SEVERAL AVENUES FOR RENEWED FOCUS IN THE PATHOPHYSIOLOGY OF AGEING AND AGE-RELATED DISEASE (I.E. DIET-MICROBIOME-HEALTH AXIS, OXIDATIVE PROTEIN DAMAGE, ADAPTIVE HOMOEOSTASIS AND PLANETARY HEALTH). WE PROPOSE THAT A BIOMIMETIC ALLIANCE WITH COLLABORATIVE RESEARCH FROM DIFFERENT DISCIPLINES CAN IMPROVE OUR UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES WITH LONG-TERM SUSTAINABLE UTILITY. 2021 19 1453 19 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 20 1865 37 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