1 2703 117 EXERCISE ADAPTATIONS: MOLECULAR MECHANISMS AND POTENTIAL TARGETS FOR THERAPEUTIC BENEFIT. EXERCISE IS FUNDAMENTAL FOR GOOD HEALTH, WHEREAS PHYSICAL INACTIVITY UNDERPINS MANY CHRONIC DISEASES OF MODERN SOCIETY. IT IS WELL APPRECIATED THAT REGULAR EXERCISE IMPROVES METABOLISM AND THE METABOLIC PHENOTYPE IN A NUMBER OF TISSUES. THE PHENOTYPIC ALTERATIONS OBSERVED IN SKELETAL MUSCLE ARE PARTLY MEDIATED BY TRANSCRIPTIONAL RESPONSES THAT OCCUR FOLLOWING EACH INDIVIDUAL BOUT OF EXERCISE. THIS ADAPTIVE RESPONSE INCREASES OXIDATIVE CAPACITY AND INFLUENCES THE FUNCTION OF MYOKINES AND EXTRACELLULAR VESICLES THAT SIGNAL TO OTHER TISSUES. OUR UNDERSTANDING OF THE EPIGENETIC AND TRANSCRIPTIONAL MECHANISMS THAT MEDIATE THE SKELETAL MUSCLE GENE EXPRESSION RESPONSE TO EXERCISE AS WELL AS OF THEIR UPSTREAM SIGNALLING PATHWAYS HAS ADVANCED SUBSTANTIALLY IN THE PAST 10 YEARS. WITH THIS KNOWLEDGE ALSO COMES THE OPPORTUNITY TO DESIGN NEW THERAPEUTIC STRATEGIES BASED ON THE BIOLOGY OF EXERCISE FOR A VARIETY OF CHRONIC CONDITIONS WHERE REGULAR EXERCISE MIGHT BE A CHALLENGE. THIS REVIEW PROVIDES AN OVERVIEW OF THE BENEFICIAL ADAPTIVE RESPONSES TO EXERCISE AND DETAILS THE MOLECULAR MECHANISMS INVOLVED. THE POSSIBILITY OF DESIGNING THERAPEUTIC INTERVENTIONS BASED ON THESE MOLECULAR MECHANISMS IS ADDRESSED, USING RELEVANT EXAMPLES THAT HAVE EXPLOITED THIS APPROACH. 2020 2 5069 29 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 3 3404 37 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 4 2562 31 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 5 3581 39 IMPACT OF PHYSICAL ACTIVITY AND EXERCISE ON THE EPIGENOME IN SKELETAL MUSCLE AND EFFECTS ON SYSTEMIC METABOLISM. EXERCISE AND PHYSICAL ACTIVITY INDUCES PHYSIOLOGICAL RESPONSES IN ORGANISMS, AND ADAPTATIONS IN SKELETAL MUSCLE, WHICH IS BENEFICIAL FOR MAINTAINING HEALTH AND PREVENTING AND/OR TREATING MOST CHRONIC DISEASES. THESE ADAPTATIONS ARE MAINLY INSTIGATED BY TRANSCRIPTIONAL RESPONSES THAT ENSUE IN REACTION TO EACH INDIVIDUAL EXERCISE, EITHER RESISTANCE OR ENDURANCE. CONSEQUENTLY, CHANGES IN KEY METABOLIC, REGULATORY, AND MYOGENIC GENES IN SKELETAL MUSCLE OCCUR AS BOTH AN EARLY AND LATE RESPONSE TO EXERCISE, AND THESE EPIGENETIC MODIFICATIONS, WHICH ARE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS, TRIGGER THOSE ALTERATIONS IN THE TRANSCRIPTIONAL RESPONSES. DNA METHYLATION AND HISTONE MODIFICATIONS ARE THE MOST SIGNIFICANT EPIGENETIC CHANGES DESCRIBED IN GENE TRANSCRIPTION, LINKED TO THE SKELETAL MUSCLE TRANSCRIPTIONAL RESPONSE TO EXERCISE, AND MEDIATING THE EXERCISE ADAPTATIONS. NEVERTHELESS, OTHER ALTERATIONS IN THE EPIGENETICS MARKERS, SUCH AS EPITRANSCRIPTOMICS, MODIFICATIONS MEDIATED BY MIRNAS, AND LACTYLATION AS A NOVEL EPIGENETIC MODIFICATION, ARE EMERGING AS KEY EVENTS FOR GENE TRANSCRIPTION. HERE, WE PROVIDE AN OVERVIEW AND UPDATE OF THE IMPACT OF EXERCISE ON EPIGENETIC MODIFICATIONS, INCLUDING THE WELL-DESCRIBED DNA METHYLATIONS AND HISTONE MODIFICATIONS, AND THE EMERGING MODIFICATIONS IN THE SKELETAL MUSCLE. IN ADDITION, WE DESCRIBE THE EFFECTS OF EXERCISE ON EPIGENETIC MARKERS IN OTHER METABOLIC TISSUES; ALSO, WE PROVIDE INFORMATION ABOUT HOW SYSTEMIC METABOLISM OR ITS METABOLITES INFLUENCE EPIGENETIC MODIFICATIONS IN THE SKELETAL MUSCLE. 2022 6 5071 38 PHYSICAL EXERCISE AND EPIGENETIC ADAPTATIONS OF THE CARDIOVASCULAR SYSTEM. DURING THE LAST DECADE, EPIGENETICS BECAME ONE OF THE FASTEST GROWING RESEARCH FIELDS IN NUMEROUS CLINICAL AND BASIC SCIENCE DISCIPLINES. EVIDENCE SUGGESTS THAT CHROMATIN MODIFICATIONS (E.G., HISTONE MODIFICATIONS AND DNA METHYLATION) AS WELL AS THE EXPRESSION OF MICRO-RNA MOLECULES PLAY A CRUCIAL ROLE IN THE PATHOGENESIS OF SEVERAL CARDIOVASCULAR DISEASES. ON THE ONE HAND, THEY ARE INVOLVED IN THE DEVELOPMENT OF GENERAL RISK FACTORS LIKE CHRONIC INFLAMMATION, BUT ON THE OTHER HAND, EPIGENETIC MODIFICATIONS ARE CONDUCIVE TO SMOOTH MUSCLE CELL, CARDIOMYOCYTE, AND ENDOTHELIAL PROGENITOR CELL PROLIFERATION/DIFFERENTIATION AS WELL AS TO EXTRACELLULAR MATRIX PROCESSING AND ENDOTHELIAL FUNCTION (E.G., ENDOTHELIAL NITRIC OXIDE SYNTHASE REGULATION). THEREFORE, EPIGENETIC MEDICAL DRUGS HAVE GAINED INCREASED ATTENTION AND PROVIDED THE FIRST PROMISING RESULTS IN THE CONTEXT OF CARDIOVASCULAR MALIGNANCIES. BESIDE OTHER LIFESTYLE FACTORS, PHYSICAL ACTIVITY AND SPORTS ESSENTIALLY CONTRIBUTE TO CARDIOVASCULAR HEALTH AND REGENERATION. IN THIS REVIEW WE FOCUS ON RECENT RESEARCH PROPOSING PHYSICAL ACTIVITY AS A POTENT EPIGENETIC REGULATOR THAT HAS THE POTENTIAL TO COUNTERACT PATHOPHYSIOLOGICAL ALTERATIONS IN ALMOST ALL THE AFOREMENTIONED CARDIOVASCULAR CELLS AND TISSUES. AS WITH EPIGENETIC MEDICAL DRUGS, MORE KNOWLEDGE ABOUT THE MOLECULAR MECHANISMS AND DOSE-RESPONSE RELATIONSHIPS OF EXERCISE IS NEEDED TO OPTIMIZE THE OUTCOME OF PREVENTIVE AND REHABILITATIVE EXERCISE PROGRAMS AND RECOMMENDATIONS. 2015 7 4273 34 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 8 724 28 CAN GENETICS GUIDE EXERCISE PRESCRIPTIONS IN OSTEOARTHRITIS? OSTEOARTHRITIS (OA) IS THE MOST COMMON FORM OF ARTHRITIS AND HAS A MULTIFACTORIAL ETIOLOGY. CURRENT MANAGEMENT FOR OA FOCUSES ON MINIMIZING PAIN AND FUNCTIONAL LOSS, TYPICALLY INVOLVING PHARMACOLOGICAL, PHYSICAL, PSYCHOSOCIAL, AND MIND-BODY INTERVENTIONS. HOWEVER, THERE REMAIN CHALLENGES IN DETERMINING WHICH PATIENTS WILL BENEFIT MOST FROM WHICH INTERVENTIONS. ALTHOUGH EXERCISE-BASED INTERVENTIONS ARE RECOMMENDED AS FIRST-LINE TREATMENTS AND ARE KNOWN TO BE BENEFICIAL FOR MANAGING BOTH THE DISEASE AND ILLNESS OF OA, THE OPTIMAL EXERCISE "PRESCRIPTION" IS UNKNOWN, DUE IN PART TO OUR LIMITED UNDERSTANDING OF THE PRECISE MECHANISMS UNDERLYING ITS ACTION. HERE WE PRESENT OUR PERSPECTIVE ON THE POTENTIAL ROLE OF GENETICS IN GUIDING EXERCISE PRESCRIPTION FOR PERSONS WITH OA. WE DESCRIBE KEY PUBLICATIONS IN THE AREAS OF EXERCISE AND OA, GENETICS AND OA, AND EXERCISE AND GENETICS, AND POINT TO A PAUCITY OF KNOWLEDGE AT THE INTERSECTION OF EXERCISE, GENETICS, AND OA. WE SUGGEST THERE IS EMERGING EVIDENCE TO SUPPORT THE USE OF GENETICS AND EPIGENETICS TO EXPLAIN THE BENEFICIAL EFFECTS OF EXERCISE FOR OA. WE IDENTIFY MISSING LINKS IN THE EXISTING RESEARCH RELATING TO EXERCISE, GENETICS, AND OA, AND HIGHLIGHT EPIGENETICS AS A PROMISING MECHANISM THROUGH WHICH ENVIRONMENTAL EXPOSURES SUCH AS EXERCISE MAY IMPACT OA OUTCOMES. WE ANTICIPATE FUTURE STUDIES WILL IMPROVE OUR UNDERSTANDING OF HOW GENETIC AND EPIGENETIC FACTORS MEDIATE EXERCISE-BASED INTERVENTIONS TO SUPPORT IMPLEMENTATION AND ULTIMATELY IMPROVE OA PATIENT CARE. 2022 9 3684 38 INFLAMMATION, PHYSICAL ACTIVITY, AND CHRONIC DISEASE: AN EVOLUTIONARY PERSPECTIVE. LOW-GRADE INFLAMMATION IS EMERGING AS A COMMON FEATURE OF CONTEMPORARY METABOLIC, PSYCHIATRIC, AND NEURODEGENERATIVE DISEASES. BOTH PHYSICAL INACTIVITY AND ABDOMINAL ADIPOSITY ARE ASSOCIATED WITH PERSISTENT SYSTEMIC LOW-GRADE INFLAMMATION. THUS, THE BEHAVIORAL, BIOLOGICAL, AND PHYSIOLOGICAL CHANGES THAT CAUSE A PREDISPOSITION TO OBESITY AND OTHER CO-MORBIDITIES COULD HAVE EPIGENETIC UNDERPINNINGS IN ADDITION TO VARIOUS EVOLUTIONARY SCENARIOS. A KEY ASSUMPTION INVOLVES THE POTENTIAL FOR A MISMATCH BETWEEN THE HUMAN GENOME MOLDED OVER GENERATIONS, AND THE ISSUE OF ADAPTING TO THE MODERN HIGH CALORIE DIET AND COMMON BUILT ENVIRONMENTS PROMOTING INACTIVITY. THIS BIOLOGICAL MISMATCH APPEARS TO HAVE DIRE HEALTH CONSEQUENCES. THEREFORE, THE GOAL OF THIS ARTICLE IS TO PROVIDE A BRIEF OVERVIEW ON THE IMPORTANCE OF INFLAMMATION AS PART OF HUMAN SURVIVAL AND HOW PHYSICAL ACTIVITY (PA) AND PHYSICAL INACTIVITY ARE CRITICAL REGULATORS OF SYSTEMIC INFLAMMATION. THE REVIEW WILL HIGHLIGHT ANTI-INFLAMMATORY EFFECTS OF PA AND EXERCISE TRAINING FROM A METABOLIC AND SYSTEMIC SIGNALING PERSPECTIVE, WHICH INCLUDES SKELETAL MUSCLE TO UTILIZATION OF FATTY ACIDS, TLR4 SIGNALING, AND MYOKINE/ADIPOKINE EFFECTS. THE AVAILABLE EVIDENCE SUGGESTS THAT PA, REGULAR EXERCISE, AND WEIGHT LOSS OFFER BOTH PROTECTION AGAINST AND TREATMENT FOR A WIDE VARIETY OF CHRONIC DISEASES ASSOCIATED WITH LOW-GRADE INFLAMMATION THROUGH AN IMPROVED INFLAMMATORY PROFILE. 2020 10 6211 32 THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTH AND DISEASE: POTENTIAL ROLE OF AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS. OXIDATIVE STRESS CAN BE INDUCED BY VARIOUS STIMULI AND ALTERED IN CERTAIN CONDITIONS, INCLUDING EXERCISE AND PAIN. ALTHOUGH MANY STUDIES HAVE INVESTIGATED OXIDATIVE STRESS IN RELATION TO EITHER EXERCISE OR PAIN, THE LITERATURE PRESENTS CONFLICTING RESULTS. THEREFORE, THIS REVIEW CRITICALLY DISCUSSES EXISTING LITERATURE ABOUT THIS TOPIC, AIMING TO PROVIDE A CLEAR OVERVIEW OF KNOWN INTERACTIONS BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTHY PEOPLE AS WELL AS IN PEOPLE WITH CHRONIC PAIN, AND TO HIGHLIGHT POSSIBLE CONFOUNDING FACTORS TO KEEP IN MIND WHEN REFLECTING ON THESE INTERACTIONS. IN ADDITION, AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS ARE PROPOSED AS POTENTIAL MECHANISMS OF ACTION UNDERLYING THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN. THIS REVIEW HIGHLIGHTS THAT THE RELATION BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IS POORLY UNDERSTOOD AND NOT STRAIGHTFORWARD, AS IT IS DEPENDENT ON THE CHARACTERISTICS OF EXERCISE, BUT ALSO ON WHICH POPULATION IS INVESTIGATED. TO BE ABLE TO COMPARE STUDIES ON THIS TOPIC, STRICT GUIDELINES SHOULD BE DEVELOPED TO LIMIT THE EFFECT OF SEVERAL CONFOUNDING FACTORS. THIS WAY, THE TRUE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN, AND THE UNDERLYING MECHANISMS OF ACTION CAN BE REVEALED AND VALIDATED VIA INDEPENDENT STUDIES. 2020 11 2704 26 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 12 2346 31 EPIGENETIC REGULATION OF METABOLISM AND INFLAMMATION BY CALORIE RESTRICTION. CHRONIC CALORIC RESTRICTION (CR) WITHOUT MALNUTRITION IS KNOWN TO AFFECT DIFFERENT CELLULAR PROCESSES SUCH AS STEM CELL FUNCTION, CELL SENESCENCE, INFLAMMATION, AND METABOLISM. DESPITE THE DIFFERENCES IN THE IMPLEMENTATION OF CR, THE REDUCTION OF CALORIES PRODUCES A WIDESPREAD BENEFICIAL EFFECT IN NONCOMMUNICABLE CHRONIC DISEASES, WHICH CAN BE EXPLAINED BY IMPROVEMENTS IN IMMUNO-METABOLIC ADAPTATION. CELLULAR ADAPTATION THAT OCCURS IN RESPONSE TO DIETARY PATTERNS CAN BE EXPLAINED BY ALTERATIONS IN EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, HISTONE MODIFICATIONS, AND MICRORNA. IN THIS REVIEW, WE DEFINE THESE MODIFICATIONS AND SYSTEMATICALLY SUMMARIZE THE CURRENT EVIDENCE RELATED TO CR AND THE EPIGENOME. WE THEN EXPLAIN THE SIGNIFICANCE OF GENOME-WIDE EPIGENETIC MODIFICATIONS IN THE CONTEXT OF DISEASE DEVELOPMENT. ALTHOUGH SUBSTANTIAL EVIDENCE EXISTS FOR THE WIDESPREAD EFFECT OF CR ON LONGEVITY, THERE IS NO CONSENSUS REGARDING THE EPIGENETIC REGULATIONS OF THE UNDERLYING CELLULAR MECHANISMS THAT LEAD TO IMPROVED HEALTH. WE PROVIDE COMPELLING EVIDENCE THAT CR PRODUCES LONG-LASTING EPIGENETIC EFFECTS THAT MEDIATE EXPRESSION OF GENES RELATED TO IMMUNO-METABOLIC PROCESSES. EPIGENETIC REPROGRAMMING OF THE UNDERLYING CHRONIC LOW-GRADE INFLAMMATION BY CR CAN LEAD TO IMMUNO-METABOLIC ADAPTATIONS THAT ENHANCE QUALITY OF LIFE, EXTEND LIFESPAN, AND DELAY CHRONIC DISEASE ONSET. 2019 13 2360 31 EPIGENETIC REGULATION OF SKELETAL MUSCLE METABOLISM. NORMAL SKELETAL MUSCLE METABOLISM IS ESSENTIAL FOR WHOLE BODY METABOLIC HOMOEOSTASIS AND DISRUPTIONS IN MUSCLE METABOLISM ARE ASSOCIATED WITH A NUMBER OF CHRONIC DISEASES. TRANSCRIPTIONAL CONTROL OF METABOLIC ENZYME EXPRESSION IS A MAJOR REGULATORY MECHANISM FOR MUSCLE METABOLIC PROCESSES. SUBSTANTIAL EVIDENCE IS EMERGING THAT HIGHLIGHTS THE IMPORTANCE OF EPIGENETIC MECHANISMS IN THIS PROCESS. THIS REVIEW WILL EXAMINE THE IMPORTANCE OF EPIGENETICS IN THE REGULATION OF MUSCLE METABOLISM, WITH A PARTICULAR EMPHASIS ON DNA METHYLATION AND HISTONE ACETYLATION AS EPIGENETIC CONTROL POINTS. THE EMERGING CROSS-TALK BETWEEN METABOLISM AND EPIGENETICS IN THE CONTEXT OF HEALTH AND DISEASE WILL ALSO BE EXAMINED. THE CONCEPT OF INHERITANCE OF SKELETAL MUSCLE METABOLIC PHENOTYPES WILL BE DISCUSSED, IN ADDITION TO EMERGING EPIGENETIC THERAPIES THAT COULD BE USED TO ALTER MUSCLE METABOLISM IN CHRONIC DISEASE STATES. 2016 14 6715 33 VITAMIN A AND THE EPIGENOME. THE EPIGENETIC PHENOMENA REFER TO HERITABLE CHANGES IN GENE EXPRESSION OTHER THAN THOSE IN THE DNA SEQUENCE, SUCH AS DNA METHYLATION AND HISTONE MODIFICATIONS. MAJOR RESEARCH PROGRESS IN THE LAST FEW YEARS HAS PROVIDED FURTHER PROOF THAT ENVIRONMENTAL FACTORS, INCLUDING DIET AND NUTRITION, CAN INFLUENCE PHYSIOLOGIC AND PATHOLOGIC PROCESSES THROUGH EPIGENETIC ALTERATIONS, WHICH IN TURN INFLUENCE GENE EXPRESSION. THIS INFLUENCE IS TERMED NUTRITIONAL EPIGENETICS, AND ONE PROMINENT EXAMPLE IS THE REGULATION OF GENE TRANSCRIPTION BY VITAMIN A THROUGH INTERACTION TO ITS NUCLEAR RECEPTOR. VITAMIN A IS CRITICAL THROUGHOUT LIFE. TOGETHER WITH ITS DERIVATIVES, IT REGULATES DIVERSE PROCESSES INCLUDING REPRODUCTION, EMBRYOGENESIS, VISION, GROWTH, CELLULAR DIFFERENTIATION AND PROLIFERATION, MAINTENANCE OF EPITHELIAL CELLULAR INTEGRITY AND IMMUNE FUNCTION. HERE WE REVIEW THE EPIGENETIC ROLE OF VITAMIN A IN CANCER, STEM CELLS DIFFERENTIATION, PROLIFERATION, AND IMMUNITY. THE DATA PRESENTED HERE SHOW THAT RETINOIC ACID IS A POTENT AGENT CAPABLE OF INDUCING ALTERATIONS IN EPIGENETIC MODIFICATIONS THAT PRODUCE VARIOUS EFFECTS ON THE PHENOTYPE. MEDICAL BENEFITS OF VITAMIN A AS AN EPIGENETIC MODULATOR, ESPECIALLY WITH RESPECT TO ITS CHRONIC USE AS NUTRITIONAL SUPPLEMENT, SHOULD RELY ON OUR FURTHER UNDERSTANDING OF ITS EPIGENETIC EFFECTS DURING HEALTH AND DISEASE, AS WELL AS THROUGH DIFFERENT GENERATIONS. 2017 15 2333 32 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 16 6034 35 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020 17 806 33 CHALLENGES FOR MODELING AND INTERPRETING THE COMPLEX BIOLOGY OF SEVERE INJURY AND INFLAMMATION. HUMAN INJURY IS ASSOCIATED WITH INFLAMMATORY RESPONSES THAT ARE MODULATED BY THE ACUTE AND CHRONIC ACTIVITY OF ENDOGENOUS FACTORS AND EXOGENOUS INTERVENTIONS. A CHARACTERISTIC FEATURE OF CHRONIC, SEVERE INFLAMMATORY STATES IS THE DIMINISHED SIGNAL OUTPUT VARIABILITY OF MANY ORGAN SYSTEMS, INCLUDING INNATE IMMUNE RESPONSIVENESS AND ENDOGENOUS NEURAL AND ENDOCRINE-MEDIATED FUNCTIONS. THE ATTENUATION OF SIGNAL/RESPONSE VARIABILITY AND INTEGRATION OF FEEDBACK CAPACITY MAY CONTRIBUTE TO SYSTEMIC AND TISSUE-SPECIFIC DETERIORATION OF FUNCTION. SOME WELL-INTENTIONED THERAPIES DIRECTED TOWARD SUPPORT OF SYSTEMIC AND TISSUE FUNCTIONS MAY ACTUALLY PROMOTE THE LOSS OF SYSTEM(S) ADAPTABILITY AND CONTRIBUTE TO ADVERSE OUTCOMES IN SEVERELY STRESSED PATIENTS. IN VIVO AND IN SILICO MODELS OF STRESS, INJURY, AND INFECTION HAVE YET TO FULLY DEFINE THE INFLUENCES OF ONGOING STRESSFUL STIMULAE AS WELL AS GENETIC VARIATION AND EPIGENETIC FACTORS IN THE CONTEXT OF AN EVOLVING INFLAMMATORY STATE. EXPERIMENTAL AND HUMAN MODELS INCORPORATING VARIABLE, ANTECEDENT STRESS(ES) AND ALTERED NEUROENDOCRINE RHYTHMS MIGHT APPROXIMATE THE ALTERED ADAPTABILITY IN IMMUNE AND ORGAN FUNCTION RESPONSES. SUCH MODELS MAY ALSO PROVIDE INSIGHTS INTO THE SALIENT MECHANISMS OF RISK AND OUTCOME MORE PRECISELY THAN DO THE CONSTRAINED STUDY CONDITIONS OF CURRENT ANIMAL OR HUMAN MODELS OF SYSTEMIC INFLAMMATION. 2008 18 5376 42 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 19 2154 40 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 20 2499 26 EPIGENETICS AND EXERCISE. EPIGENETICS CAN BE DEFINED AS 'THE STRUCTURAL ADAPTATION OF CHROMOSOMAL REGIONS SO AS TO REGISTER, SIGNAL, OR PERPETUATE ALTERED ACTIVITY STATES.' INCREASED TRANSCRIPTION OF KEY REGULATORY, METABOLIC, AND MYOGENIC GENES IS AN EARLY RESPONSE TO EXERCISE AND IS IMPORTANT IN MEDIATING SUBSEQUENT ADAPTATIONS IN SKELETAL MUSCLE. DNA HYPOMETHYLATION AND HISTONE HYPERACETYLATION ARE EMERGING AS IMPORTANT CRUCIAL EVENTS FOR INCREASED TRANSCRIPTION. THE COMPLEX INTERACTIONS BETWEEN MULTIPLE EPIGENETIC MODIFICATIONS AND THEIR REGULATION BY METABOLIC CHANGES AND SIGNALING EVENTS DURING EXERCISE, WITH IMPLICATIONS FOR ENHANCED UNDERSTANDING OF THE ACUTE AND CHRONIC ADAPTATIONS TO EXERCISE, ARE QUESTIONS FOR FURTHER INVESTIGATION. 2019