1 3689 96 INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE AND THEIR MANAGEMENT BY NATURAL BIOACTIVE COMPOUNDS. AUTOIMMUNE DISEASES ARE CAUSED BY THE OVERACTIVITY OF THE IMMUNE SYSTEM TOWARDS SELF-CONSTITUENTS. RISK FACTORS OF AUTOIMMUNE DISEASES ARE MULTIPLE AND INCLUDE GENETIC, EPIGENETIC, ENVIRONMENTAL, AND PSYCHOLOGICAL. AUTOIMMUNE CHRONIC INFLAMMATORY BOWEL DISEASES, INCLUDING CELIAC AND INFLAMMATORY DISEASES (CROHN'S DISEASE AND ULCERATIVE COLITIS), CONSTITUTE A SIGNIFICANT HEALTH PROBLEM WORLDWIDE. BESIDES THE COMPLEXITY OF THE SYMPTOMS OF THESE DISEASES, THEIR TREATMENTS HAVE ONLY BEEN PALLIATIVE. NUMEROUS INVESTIGATIONS SHOWED THAT NATURAL PHYTOCHEMICALS COULD BE PROMISING STRATEGIES TO FIGHT AGAINST THESE AUTOIMMUNE DISEASES. IN THIS RESPECT, PLANT-DERIVED NATURAL COMPOUNDS SUCH AS FLAVONOIDS, PHENOLIC ACIDS, AND TERPENOIDS EXHIBITED SIGNIFICANT EFFECTS AGAINST THREE AUTOIMMUNE DISEASES AFFECTING THE INTESTINE, PARTICULARLY BOWEL DISEASES. THIS REVIEW FOCUSES ON THE ROLE OF NATURAL COMPOUNDS OBTAINED FROM MEDICINAL PLANTS IN MODULATING INFLAMMATORY AUTO-IMMUNE DISEASES OF THE INTESTINE. IT COVERS THE MOST RECENT LITERATURE RELATED TO THE EFFECT OF THESE NATURAL COMPOUNDS IN THE TREATMENT AND PREVENTION OF AUTO-IMMUNE DISEASES OF THE INTESTINE. 2022 2 1404 29 DIETARY COMPOSITION AND EFFECTS IN INFLAMMATORY BOWEL DISEASE. DRAMATIC CHANGES IN THE ENVIRONMENT AND HUMAN LIFESTYLE HAVE BEEN ASSOCIATED WITH THE RISE OF VARIOUS CHRONIC COMPLEX DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD). A DYSBIOTIC GUT MICROBIOTA HAS BEEN PROPOSED AS A CRUCIAL PATHOGENIC ELEMENT, CONTRIBUTING TO IMMUNE IMBALANCES AND FOSTERING A PROINFLAMMATORY MILIEU, WHICH MAY BE ASSOCIATED WITH DISEASE RELAPSES OR EVEN THE INITIATION OF IBD. IN ADDITION TO REPRESENTING IMPORTANT REGULATORS OF THE MUCOSAL IMMUNITY AND THE COMPOSITION OF THE GUT MICROBIOTA, FOOD COMPONENTS HAVE BEEN SHOWN TO BE POTENTIAL ENVIRONMENTAL TRIGGERS OF EPIGENETIC MODIFICATIONS. IN THE CONTEXT OF CHRONIC INTESTINAL INFLAMMATION, DIETARY HABITS AND SPECIFIC FOOD COMPONENTS HAVE BEEN IMPLICATED AS IMPORTANT MODULATORS OF EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, WHICH MAY PREDISPOSE A PERSON TO THE INCREASED RISK OF THE INITIATION AND EVOLUTION OF IBD. THIS REVIEW PROVIDES NOVEL INSIGHTS ABOUT HOW DIETARY FACTORS MAY INTERACT WITH THE INTESTINAL MUCOSA AND MODULATE IMMUNE HOMEOSTASIS BY SHAPING THE INTESTINAL ECOSYSTEM, AS WELL AS THE POTENTIAL INFLUENCE OF DIET IN THE ETIOPATHOGENESIS AND MANAGEMENT OF IBD. 2019 3 566 34 BASES FOR THE ADEQUATE DEVELOPMENT OF NUTRITIONAL RECOMMENDATIONS FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC AND RELAPSING INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT; IT IS A HETEROGENEOUS AND MULTIFACTORIAL DISORDER RESULTING FROM A COMPLEX INTERPLAY BETWEEN GENETIC VARIATION, INTESTINAL MICROBIOTA, THE HOST IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS SUCH AS DIET, DRUGS, BREASTFEEDING AND SMOKING. THE INTERACTIONS BETWEEN DIETARY NUTRIENTS AND INTESTINAL IMMUNITY ARE COMPLEX. THERE IS A COMPELLING ARGUMENT FOR ENVIRONMENTAL FACTORS SUCH AS DIET PLAYING A ROLE IN THE CAUSE AND COURSE OF IBD, GIVEN THAT THREE IMPORTANT FACTORS IN THE PATHOGENESIS OF IBD CAN BE MODULATED AND CONTROLLED BY DIET: INTESTINAL MICROBIOTA, THE IMMUNE SYSTEM AND EPITHELIAL BARRIER FUNCTION. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE EPIDEMIOLOGICAL FINDINGS REGARDING DIET AND TO FOCUS ON THE EFFECTS THAT NUTRIENTS EXERT ON THE INTESTINAL MUCOSA-MICROBIOTA-PERMEABILITY INTERACTION. THE NATURE OF THESE INTERACTIONS IN IBD IS INFLUENCED BY ALTERATIONS IN THE NUTRITIONAL METABOLISM OF THE GUT MICROBIOTA AND HOST CELLS THAT CAN INFLUENCE THE OUTCOME OF NUTRITIONAL INTERVENTION. A BETTER UNDERSTANDING OF DIET-HOST-MICROBIOTA INTERACTIONS IS ESSENTIAL FOR UNRAVELLING THE COMPLEX MOLECULAR BASIS OF EPIGENETIC, GENETIC AND ENVIRONMENTAL INTERACTIONS UNDERLYING IBD PATHOGENESIS AS WELL AS FOR OFFERING NEW THERAPEUTIC APPROACHES FOR THE TREATMENT OF IBD. 2019 4 6333 28 THE ROLE OF DIETARY PHENOLIC COMPOUNDS IN EPIGENETIC MODULATION INVOLVED IN INFLAMMATORY PROCESSES. A BETTER UNDERSTANDING OF THE INTERACTIONS BETWEEN DIETARY PHENOLIC COMPOUNDS AND THE EPIGENETICS OF INFLAMMATION MAY IMPACT PATHOLOGICAL CONDITIONS AND THEIR TREATMENT. PHENOLIC COMPOUNDS ARE WELL-KNOWN FOR THEIR ANTIOXIDANT, ANTI-INFLAMMATORY, ANTI-ANGIOGENIC, AND ANTI-CANCER PROPERTIES, WITH POTENTIAL BENEFITS IN THE TREATMENT OF VARIOUS HUMAN DISEASES. EMERGING STUDIES BRING EVIDENCE THAT NUTRITION MAY PLAY AN ESSENTIAL ROLE IN IMMUNE SYSTEM MODULATION ALSO BY ALTERING GENE EXPRESSION. THIS REVIEW DISCUSSES EPIGENETIC MECHANISMS SUCH AS DNA METHYLATION, POST-TRANSLATIONAL HISTONE MODIFICATION, AND NON-CODING MICRORNA ACTIVITY THAT REGULATE THE GENE EXPRESSION OF MOLECULES INVOLVED IN INFLAMMATORY PROCESSES. SPECIAL ATTENTION IS PAID TO THE MOLECULAR BASIS OF NF-KAPPAB MODULATION BY DIETARY PHENOLIC COMPOUNDS. THE REGULATION OF HISTONE ACETYLTRANSFERASE AND HISTONE DEACETYLASE ACTIVITY, WHICH ALL INFLUENCE NF-KAPPAB SIGNALING, SEEMS TO BE A CRUCIAL MECHANISM OF THE EPIGENETIC CONTROL OF INFLAMMATION BY PHENOLIC COMPOUNDS. MOREOVER, CHRONIC INFLAMMATORY PROCESSES ARE REPORTED TO BE CLOSELY CONNECTED TO THE MAJOR STAGES OF CARCINOGENESIS AND OTHER NON-COMMUNICABLE DISEASES. THEREFORE, DIETARY PHENOLIC COMPOUNDS-TARGETED EPIGENETICS IS BECOMING AN ATTRACTIVE APPROACH FOR DISEASE PREVENTION AND INTERVENTION. 2020 5 2100 29 EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS: A FOCUS ON SIRT1-MEDIATED MECHANISMS. POLYPHENOLS ARE A CLASS OF NATURAL COMPOUNDS WIDELY DISTRIBUTED IN FRUITS, VEGETABLES, AND PLANTS. THEY HAVE BEEN REPORTED TO POSSESS A WIDE RANGE OF ACTIVITIES IN PREVENTION AND ALLEVIATION OF VARIOUS DISEASES LIKE CANCER, NEUROINFLAMMATION, DIABETES, AND AGING. POLYPHENOLS ARE EFFECTIVE AGAINST CHRONIC DISEASES AND RECENT REPORTS INDICATED STRONG EPIGENETIC EFFECTS OF POLYPHENOLS. MOST OF THE STUDIES INVESTIGATING EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS HAVE FOCUSED ON THEIR BENEFICIAL EFFECTS IN CANCER TREATMENT. HOWEVER, EPIGENETIC DEFECTS HAVE BEEN DEMONSTRATED IN MANY OTHER DISEASES AS WELL, AND APPLICATION OF POLYPHENOLS TO MODULATE THE EPIGENOME IS BECOMING AN INTERESTING FIELD OF RESEARCH. THIS REVIEW SUMMARIZES THE EFFECTS OF NATURAL POLYPHENOLS IN MODULATING EPIGENETIC-RELATED ENZYMES AS WELL AS THEIR EFFECT IN PREVENTION AND TREATMENT OF CHRONIC DISEASES WITH A FOCUS ON SIRT1 MODULATION. WE HAVE ALSO DISCUSSED THE RELATION BETWEEN THE STRUCTURE AND FUNCTION OF EPIGENETIC-MODIFYING POLYPHENOLS. 2014 6 2675 26 ETIOPATHOGENESIS OF INFLAMMATORY BOWEL DISEASE: TODAY AND TOMORROW. PURPOSE OF REVIEW: CROHN'S DISEASE AND ULCERATIVE COLITIS, THE TWO MAJOR FORMS OF INFLAMMATORY BOWEL DISEASE (IBD), REPRESENT CHRONIC DISEASES OF UNKNOWN CAUSE, AND THEY ARE REGARDED AS PROTOTYPICAL COMPLEX DISEASES. DESPITE ALL THE RECENT ADVANCES, A COMPLETE APPRECIATION OF THE PATHOGENESIS OF IBD IS STILL LIMITED. IN THIS REVIEW, WE PRESENT RECENT INFORMATION CONTRIBUTING TO A BETTER UNDERSTANDING OF MECHANISMS UNDERLYING IBD. RECENT FINDINGS: HERE, WE ATTEMPT TO HIGHLIGHT NOVEL ENVIRONMENTAL TRIGGERS, DATA ON THE GUT MICROBIOTA, ITS INTERACTION WITH THE HOST, AND THE POTENTIAL INFLUENCE OF DIET AND FOOD COMPONENTS. WE DISCUSS RECENT FINDINGS ON DEFECTIVE SIGNALING PATHWAYS AND THE POTENTIAL EFFECTS ON THE IMMUNE RESPONSE, AND WE PRESENT NEW DATA ON EPIGENETIC CHANGES, INFLAMMASOME, AND DAMAGE-ASSOCIATED MOLECULAR PATTERNS ASSOCIATED WITH IBD. SUMMARY: THE CONTINUING IDENTIFICATION OF SEVERAL EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC ALTERATIONS IN PATIENTS WITH IBD REFLECTS THE COMPLEX NATURE OF THE DISEASE AND SUGGESTS THE NEED FOR INNOVATIVE APPROACHES SUCH AS SYSTEMS BIOLOGY FOR IDENTIFYING NOVEL RELEVANT TARGETS IN IBD. 2017 7 3547 37 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021 8 3541 33 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD. 2023 9 3692 31 INFLAMMATORY BOWEL DISEASES: THE ROLE OF GUT MICROBIOTA. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC MULTIFACTORIAL DISEASES CHARACTERIZED BY PARTIALLY UNCLEAR PATHOGENIC MECHANISMS INCLUDING CHANGES IN INTESTINAL MICROBIOTA. DESPITE THE MICROBIOTA, ALTERATION IS WELL ESTABLISHED IN IBD PATIENTS, AS REPORTED BY 16RNA SEQUENCING ANALYSIS, AN IMPORTANT GOAL IS TO DEFINE IF IT IS JUST A CONSEQUENCE OF THE DISEASE PROGRESSION OR A TRIGGER FACTOR OF THE DISEASE ITSELF. TO DATE, GUT MICROBIOTA COMPOSITION AND GUT MICROBIOTA-RELATED METABOLITES SEEM TO AFFECT THE HOST HEALTHY STATE BOTH BY MODULATING METABOLIC PATHWAYS OR ACTING ON THE EXPRESSION OF DIFFERENT GENES THROUGH EPIGENETIC EFFECTS. BECAUSE OF THIS, IT HAS BEEN SUGGESTED THAT INTESTINAL MICROBIOTA MIGHT REPRESENT A PROMISING THERAPEUTIC TARGET FOR IBD PATIENTS. THE AIM OF THIS REVIEW IS TO SUMMARIZE BOTH THE MOST RECENT ACQUISITIONS IN THE FIELD OF GUT MICROBIOTA AND ITS INVOLVEMENT IN INTESTINAL INFLAMMATION TOGETHER WITH THE AVAILABLE STRATEGIES FOR THE MODULATION OF MICROBIOTA, SUCH AS PREBIOTICS AND/OR PROBIOTICS ADMINISTRATION OR FECAL MICROBIOTA TRANSPLANTATION. 2020 10 4783 40 NUTRIGENOMICS IN PARKINSON'S DISEASE: DIVERSITY OF MODULATORY ACTIONS OF POLYPHENOLS ON EPIGENETIC EFFECTS INDUCED BY TOXINS. ALTHOUGH THE PATHOGENESIS OF PARKINSON'S DISEASE (PD) IS NOT COMPLETELY UNDERSTOOD, THERE IS A CONSENSUS THAT IT CAN BE CAUSED BY MULTIFACTORIAL MECHANISMS INVOLVING GENETIC SUSCEPTIBILITY, EPIGENETIC MODIFICATIONS INDUCED BY TOXINS AND MITOCHONDRIAL DYSFUNCTION. IN THE PAST 20 YEARS, GREAT EFFORTS HAVE BEEN MADE IN ORDER TO CLARIFY MOLECULAR MECHANISMS THAT ARE RISK FACTORS FOR THIS DISEASE, AS WELL AS TO IDENTIFY BIOACTIVE AGENTS FOR PREVENTION AND SLOWING DOWN OF ITS PROGRESSION. NUTRACEUTICAL PRODUCTS HAVE RECEIVED SUBSTANTIAL INTEREST DUE TO THEIR NUTRITIONAL, SAFE AND THERAPEUTIC EFFECTS ON SEVERAL CHRONIC DISEASES. THE AIM OF THIS REVIEW WAS TO GATHER THE MAIN EVIDENCE OF THE EPIGENETIC MECHANISMS INVOLVED IN THE NEUROPROTECTIVE EFFECTS OF PHENOLIC COMPOUNDS CURRENTLY UNDER INVESTIGATION FOR THE TREATMENT OF TOXIN-INDUCED PD. THESE STUDIES CONFIRM THAT THE NEUROPROTECTIVE ACTIONS OF POLYPHENOLS INVOLVE COMPLEX EPIGENETIC MODULATIONS, DEMONSTRATING THAT THE INTAKE OF THESE NATURAL COMPOUNDS CAN BE A PROMISING, LOW-COST, PHARMACOGENOMIC STRATEGY AGAINST THE DEVELOPMENT OF PD. 2023 11 554 31 AUTOPHAGY IN HUMAN HEALTH AND DISEASE: NOVEL THERAPEUTIC OPPORTUNITIES. SIGNIFICANCE: IN EUKARYOTES, AUTOPHAGY REPRESENTS A HIGHLY EVOLUTIONARY CONSERVED PROCESS, THROUGH WHICH MACROMOLECULES AND CYTOPLASMIC MATERIAL ARE DEGRADED INTO LYSOSOMES AND RECYCLED FOR BIOSYNTHETIC OR ENERGETIC PURPOSES. DYSFUNCTION OF THE AUTOPHAGIC PROCESS HAS BEEN ASSOCIATED WITH THE ONSET AND DEVELOPMENT OF MANY HUMAN CHRONIC PATHOLOGIES, SUCH AS CARDIOVASCULAR, METABOLIC, AND NEURODEGENERATIVE DISEASES AS WELL AS CANCER. RECENT ADVANCES: CURRENTLY, COMPREHENSIVE RESEARCH IS BEING CARRIED OUT TO DISCOVER NEW THERAPEUTIC AGENTS THAT ARE ABLE TO MODULATE THE AUTOPHAGIC PROCESS IN VIVO. RECENT EVIDENCE HAS SHOWN THAT A LARGE NUMBER OF NATURAL BIOACTIVE COMPOUNDS ARE INVOLVED IN THE REGULATION OF AUTOPHAGY BY MODULATING SEVERAL TRANSCRIPTIONAL FACTORS AND SIGNALING PATHWAYS. CRITICAL ISSUES: CRITICAL ISSUES THAT DESERVE PARTICULAR ATTENTION ARE THE INADEQUATE UNDERSTANDING OF THE COMPLEX ROLE OF AUTOPHAGY IN DISEASE PATHOGENESIS, THE LIMITED AVAILABILITY OF THERAPEUTIC DRUGS, AND THE LACK OF CLINICAL TRIALS. IN THIS CONTEXT, THE EFFECTS THAT NATURAL BIOACTIVE COMPOUNDS EXERT ON AUTOPHAGIC MODULATION SHOULD BE CLEARLY HIGHLIGHTED, SINCE THEY DEPEND ON THE TYPE AND STAGE OF THE PATHOLOGICAL CONDITIONS OF DISEASES. FUTURE DIRECTIONS: RESEARCH EFFORTS SHOULD NOW FOCUS ON UNDERSTANDING THE SURVIVAL-SUPPORTING AND DEATH-PROMOTING ROLES OF AUTOPHAGY, HOW NATURAL COMPOUNDS INTERACT EXACTLY WITH THE AUTOPHAGIC TARGETS SO AS TO INDUCE OR INHIBIT AUTOPHAGY AND ON THE EVALUATION OF THEIR PHARMACOLOGICAL EFFECTS IN A MORE IN-DEPTH AND MECHANISTIC WAY. IN ADDITION, CLINICAL STUDIES ON AUTOPHAGY-INDUCING NATURAL PRODUCTS ARE STRONGLY ENCOURAGED, ALSO TO HIGHLIGHT SOME FUNDAMENTAL ASPECTS, SUCH AS THE DOSE, THE DURATION, AND THE POSSIBLE SYNERGISTIC ACTION OF THESE COMPOUNDS WITH CONVENTIONAL THERAPY. 2019 12 4274 35 MICROBIOTA IN INFLAMMATORY BOWEL DISEASE PATHOGENESIS AND THERAPY: IS IT ALL ABOUT DIET? INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING ULCERATIVE COLITIS, CROHN'S DISEASE, AND UNCLASSIFIED IBD, CONTINUES TO CAUSE SIGNIFICANT MORBIDITY. WHILE ITS INCIDENCE IS INCREASING, NO CLEAR ETIOLOGY AND NO CURE HAVE YET BEEN DISCOVERED. RECENT FINDINGS SUGGEST THAT IBD MAY HAVE A MULTIFACTORIAL ETIOLOGY, WHERE COMPLEX INTERACTIONS BETWEEN GENETICS, EPIGENETICS, ENVIRONMENTAL FACTORS (INCLUDING DIET BUT ALSO INFECTIONS, ANTIBIOTICS, AND SANITATION), AND HOST IMMUNE SYSTEM LEAD TO ABNORMAL IMMUNE RESPONSES AND CHRONIC INFLAMMATION. OVER THE PAST YEARS, THE ROLE OF ALTERED GUT MICROBIOTA (IN BOTH COMPOSITION AND FUNCTION) IN IBD PATHOGENESIS HAS EMERGED AS AN OUTSTANDING AREA OF INTEREST. ACCORDING TO NEW FINDINGS, GUT DYSBIOSIS MAY APPEAR AS A KEY ELEMENT IN INITIATION OF INFLAMMATION IN IBD AND ITS COMPLICATIONS. MOREOVER, COMPLEX METAGENOMIC STUDIES PROVIDE POSSIBILITIES TO DISTINGUISH BETWEEN IBD TYPES AND APPRECIATE SEVERITY AND PROGNOSIS OF THE DISEASE, AS WELL AS RESPONSE TO THERAPY. THIS REVIEW PROVIDES AN UPDATED KNOWLEDGE OF RECENT FINDINGS LINKING ALTERED BACTERIAL COMPOSITION AND FUNCTIONS, VIRUSES, AND FUNGI TO IBD PATHOGENESIS. IT ALSO HIGHLIGHTS THE COMPLEX GENETIC, EPIGENETIC, IMMUNE, AND MICROBIAL INTERACTIONS IN RELATION TO ENVIRONMENTAL FACTORS (INCLUDING DIET). WE OVERVIEW THE ACTUAL OPTIONS TO MANIPULATE THE ALTERED MICROBIOTA, SUCH AS MODIFIED DIET, PROBIOTICS, PREBIOTICS, SYNBIOTICS, ANTIBIOTICS, AND FECAL TRANSPLANTATION. FUTURE POSSIBLE THERAPIES ARE ALSO INCLUDED. TARGETING ALTERED MICROBIOTA COULD BE THE NEXT THERAPEUTIC PERSONALIZED APPROACH, BUT MORE RESEARCH AND WELL-DESIGNED COMPARATIVE PROSPECTIVE STUDIES ARE REQUIRED TO FORMULATE ADEQUATE DIRECTIONS FOR PREVENTION AND THERAPY. 2015 13 1414 32 DIETARY PHYTOCHEMICALS IN NEUROIMMUNOAGING: A NEW THERAPEUTIC POSSIBILITY FOR HUMANS? ALTHOUGH SEVERAL EFFORTS HAVE BEEN MADE IN THE SEARCH FOR GENETIC AND EPIGENETIC PATTERNS LINKED TO DISEASES, A COMPREHENSIVE EXPLANATION OF THE MECHANISMS UNDERLYING PATHOLOGICAL PHENOTYPIC PLASTICITY IS STILL FAR FROM BEING CLARIFIED. OXIDATIVE STRESS AND INFLAMMATION ARE TWO OF THE MAJOR TRIGGERS OF THE EPIGENETIC ALTERATIONS OCCURRING IN CHRONIC PATHOLOGIES, SUCH AS NEURODEGENERATIVE DISEASES. IN FACT, OVER THE LAST DECADE, REMARKABLE PROGRESS HAS BEEN MADE TO REALIZE THAT CHRONIC, LOW-GRADE INFLAMMATION IS ONE OF THE MAJOR RISK FACTOR UNDERLYING BRAIN AGING. ACCUMULATED DATA STRONGLY SUGGEST THAT PHYTOCHEMICALS FROM FRUITS, VEGETABLES, HERBS, AND SPICES MAY EXERT RELEVANT IMMUNOMODULATORY AND/OR ANTI-INFLAMMATORY ACTIVITIES IN THE CONTEXT OF BRAIN AGING. STARTING BY THE EVIDENCE THAT A COMMON DENOMINATOR OF AGING AND CHRONIC DEGENERATIVE DISEASES IS REPRESENTED BY INFLAMMATION, AND THAT SEVERAL DIETARY PHYTOCHEMICALS ARE ABLE TO POTENTIALLY INTERFERE WITH AND REGULATE THE NORMAL FUNCTION OF CELLS, IN PARTICULAR NEURONAL COMPONENTS, AIM OF THIS REVIEW IS TO SUMMARIZE RECENT STUDIES ON NEUROINFLAMMAGING PROCESSES AND PROOFS INDICATING THAT SPECIFIC PHYTOCHEMICALS MAY ACT AS POSITIVE MODULATORS OF NEUROINFLAMMATORY EVENTS. IN ADDITION, CRITICAL PATHWAYS INVOLVED IN MEDIATING PHYTOCHEMICALS EFFECTS ON NEUROINFLAMMAGING WERE DISCUSSED, EXPLORING THE REAL IMPACT OF THESE COMPOUNDS IN PRESERVING BRAIN HEALTH BEFORE THE ONSET OF SYMPTOMS LEADING TO INFLAMMATORY NEURODEGENERATION AND COGNITIVE DECLINE. 2016 14 5540 31 ROLE OF DIET AND GUT MICROBIOTA ON COLORECTAL CANCER IMMUNOMODULATION. COLORECTAL CANCER (CRC) IS ONE OF THE MOST COMMONLY DIAGNOSED CANCERS, AND IT IS CHARACTERIZED BY GENETIC AND EPIGENETIC ALTERATIONS, AS WELL AS BY INFLAMMATORY CELL INFILTRATION AMONG MALIGNANT AND STROMAL CELLS. HOWEVER, THIS DYNAMIC INFILTRATION CAN BE INFLUENCED BY THE MICROENVIRONMENT TO PROMOTE TUMOR PROLIFERATION, SURVIVAL AND METASTASIS OR CANCER INHIBITION. IN PARTICULAR, THE CANCER MICROENVIRONMENT METABOLITES CAN REGULATE THE INFLAMMATORY CELLS TO INDUCE A CHRONIC INFLAMMATORY RESPONSE THAT CAN BE A PREDISPOSING CONDITION FOR CRC RETENTION. IN ADDITION, SOME NUTRITIONAL COMPONENTS MIGHT CONTRIBUTE TO A CHRONIC INFLAMMATORY CONDITION BY REGULATING VARIOUS IMMUNE AND INFLAMMATORY PATHWAYS. BESIDES THAT, DIET STRONGLY MODULATES THE GUT MICROBIOTA COMPOSITION, WHICH HAS A KEY ROLE IN MAINTAINING GUT HOMEOSTASIS AND IS ASSOCIATED WITH THE MODULATION OF HOST INFLAMMATORY AND IMMUNE RESPONSES. THEREFORE, DIET HAS A FUNDAMENTAL ROLE IN CRC INITIATION, PROGRESSION AND PREVENTION. IN PARTICULAR, FUNCTIONAL FOODS SUCH AS PROBIOTICS, PREBIOTICS AND SYMBIOTICS CAN HAVE A POTENTIALLY POSITIVE EFFECT ON HEALTH BEYOND BASIC NUTRITION AND HAVE ANTI-INFLAMMATORY EFFECTS. IN THIS REVIEW, WE DISCUSS THE INFLUENCE OF DIET ON GUT MICROBIOTA COMPOSITION, FOCUSING ON ITS ROLE ON GUT INFLAMMATION AND IMMUNITY. FINALLY, WE DESCRIBE THE POTENTIAL BENEFITS OF USING PROBIOTICS AND PREBIOTICS TO MODULATE THE HOST INFLAMMATORY RESPONSE, AS WELL AS ITS APPLICATION IN CRC PREVENTION AND TREATMENT. 2019 15 1395 33 DIET AND MICROBIOME IN THE BEGINNING OF THE SEQUENCE OF GUT INFLAMMATION. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT DUE, AT LEAST PARTIALLY, TO AN ABERRANT AND EXCESSIVE MUCOSAL IMMUNE RESPONSE TO GUT BACTERIA IN GENETICALLY-PREDISPOSED INDIVIDUALS UNDER CERTAIN ENVIRONMENTAL FACTORS. THE INCIDENCE OF IBD IS RISING IN WESTERN AND NEWLY INDUSTRIALIZED COUNTRIES, PARALLELING THE INCREASE OF WESTERNIZED DIETARY PATTERNS, THROUGH NEW ANTIGENS, EPITHELIAL FUNCTION AND PERMEABILITY, EPIGENETIC MECHANISMS (E.G., DNA METHYLATION), AND ALTERATION OF THE GUT MICROBIOME. ALTERATION IN THE COMPOSITION AND FUNCTIONALITY OF THE GUT MICROBIOME (INCLUDING BACTERIA, VIRUSES AND FUNGI) SEEMS TO BE A NUCLEAR PATHOGENIC FACTOR. THE MICROBIOME ITSELF IS DYNAMIC, AND THE CHANGES IN FOOD QUALITY, DIETARY HABITS, LIVING CONDITIONS AND HYGIENE OF THESE WESTERN SOCIETIES, COULD INTERACT IN A COMPLEX MANNER AS MODULATORS OF DYSBIOSIS, THEREBY INFLUENCING THE ACTIVATION OF IMMUNE CELLS' PROMOTING INFLAMMATION. THE MICROBIOME PRODUCES DIVERSE SMALL MOLECULES VIA SEVERAL METABOLIC WAYS, WITH THE FIBER-DERIVED SHORT-CHAIN FATTY ACIDS (I.E., BUTYRATE) AS MAIN ELEMENTS AND HAVING ANTI-INFLAMMATORY EFFECTS. THESE METABOLITES AND SOME MICRONUTRIENTS OF THE DIET (I.E., VITAMINS, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS) ARE REGULATORS OF INNATE AND ADAPTIVE INTESTINAL IMMUNE HOMEOSTASIS. AN EXCESSIVE AND UNHEALTHY CONSUMPTION OF SUGAR, ANIMAL FAT AND A LOW-VEGETABLE AND -FIBER DIET ARE RISK FACTORS FOR IBD APPEARANCE. FURTHERMORE, METABOLISM OF NUTRIENTS IN INTESTINAL EPITHELIUM AND IN GUT MICROBIOTA IS ALTERED BY INFLAMMATION, CHANGING THE DEMAND FOR NUTRIENTS NEEDED FOR HOMEOSTASIS. THIS ROLE OF FOOD AND A REDUCED GUT MICROBIAL DIVERSITY IN CAUSING IBD MIGHT ALSO HAVE A PROPHYLACTIC OR THERAPEUTIC ROLE FOR IBD. THE RELATIONSHIP BETWEEN DIETARY INTAKE, SYMPTOMS, AND BOWEL INFLAMMATION COULD LEAD TO DIETARY AND LIFESTYLE RECOMMENDATIONS, INCLUDING DIETS WITH ABUNDANT FRUITS, VEGETABLES, OLIVE OIL AND OILY FISH, WHICH HAVE ANTI-INFLAMMATORY EFFECTS AND COULD PREVENT DYSBIOSIS AND IBD. DIETARY MODULATION AND APPROPRIATE EXCLUSION DIETS MIGHT BE A NEW COMPLEMENTARY MANAGEMENT FOR TREATMENT AT DISEASE FLARES AND IN REFRACTORY PATIENTS, EVEN REDUCING COMPLICATIONS, HOSPITALIZATIONS AND SURGERY, THROUGH MODIFYING THE LUMINAL INTESTINAL ENVIRONMENT. 2021 16 4652 26 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 17 4273 28 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 18 1275 35 DAMAGE-ASSOCIATED MOLECULAR PATTERNS IN INFLAMMATORY BOWEL DISEASE: FROM BIOMARKERS TO THERAPEUTIC TARGETS. THE CHRONIC INFLAMMATORY PROCESS UNDERLYING INFLAMMATORY BOWEL DISEASE (IBD), COMPRISING CROHN'S DISEASE AND ULCERATIVE COLITIS, DERIVES FROM THE INTERPLAY OF SEVERAL COMPONENTS IN A GENETICALLY SUSCEPTIBLE HOST. THESE COMPONENTS INCLUDE ENVIRONMENTAL ELEMENTS AND GUT MICROBIOTA A DYSBIOSIS. FOR DECADES, IMMUNE ABNORMALITIES HAVE BEEN INVESTIGATED AS CRITICALLY IMPORTANT IN IBD PATHOGENESIS, AND ATTEMPTS TO DEVELOP EFFECTIVE THERAPIES HAVE PREDOMINANTLY TARGETED THE IMMUNE SYSTEM. NEVERTHELESS, IMMUNE EVENTS REPRESENT ONLY ONE OF THE CONSTITUENTS CONTRIBUTING TO IBD PATHOGENESIS WITHIN THE CONTEXT OF THE COMPLEX CELLULAR AND MOLECULAR NETWORK UNDERLYING CHRONIC INTESTINAL INFLAMMATION. THESE FACTORS NEED TO BE APPRECIATED WITHIN THE MILIEU OF NON-IMMUNE COMPONENTS. DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS), WHICH ARE ESSENTIALLY ENDOGENOUS STRESS PROTEINS EXPRESSED OR RELEASED AS A RESULT OF CELL OR TISSUE DAMAGE, HAVE BEEN SHOWN TO ACT AS DIRECT PRO-INFLAMMATORY MEDIATORS. EXCESSIVE OR PERSISTENT SIGNALLING MEDIATED BY SUCH MOLECULES CAN UNDERLIE SEVERAL CHRONIC INFLAMMATORY DISORDERS, INCLUDING IBD. THE RELEASE OF ENDOGENOUS DAMPS AMPLIFIES THE INFLAMMATORY RESPONSE DRIVEN BY IMMUNE AND NON-IMMUNE CELLS AND PROMOTES EPIGENETIC REPROGRAMMING IN IBD. THE EFFECTS DETERMINE PATHOLOGIC CHANGES, WHICH MAY SUSTAIN CHRONIC INTESTINAL INFLAMMATION AND ALSO UNDERLIE SPECIFIC DISEASE PHENOTYPES. IN ADDITION TO HIGHLIGHTING THE POTENTIAL USE OF DAMPS SUCH AS CALPROTECTIN AS BIOMARKERS, RESEARCH ON DAMPS MAY REVEAL NOVEL MECHANISTIC ASSOCIATIONS IN IBD PATHOGENESIS AND IS EXPECTED TO UNCOVER PUTATIVE THERAPEUTIC TARGETS. 2018 19 3016 29 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE. 2020 20 2855 35 FROM INFLAMMAGING TO HEALTHY AGING BY DIETARY LIFESTYLE CHOICES: IS EPIGENETICS THE KEY TO PERSONALIZED NUTRITION? THE PROGRESSIVELY OLDER POPULATION IN DEVELOPED COUNTRIES IS REFLECTED IN AN INCREASE IN THE NUMBER OF PEOPLE SUFFERING FROM AGE-RELATED CHRONIC INFLAMMATORY DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, HEART AND LUNG DISEASES, CANCER, OSTEOPOROSIS, ARTHRITIS, AND DEMENTIA. THE HETEROGENEITY IN BIOLOGICAL AGING, CHRONOLOGICAL AGE, AND AGING-ASSOCIATED DISORDERS IN HUMANS HAVE BEEN ASCRIBED TO DIFFERENT GENETIC AND ENVIRONMENTAL FACTORS (I.E., DIET, POLLUTION, STRESS) THAT ARE CLOSELY LINKED TO SOCIOECONOMIC FACTORS. THE COMMON DENOMINATOR OF THESE FACTORS IS THE INFLAMMATORY RESPONSE. CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION DURING PHYSIOLOGICAL AGING AND IMMUNOSENESCENCE ARE INTERTWINED IN THE PATHOGENESIS OF PREMATURE AGING ALSO DEFINED AS 'INFLAMMAGING.' THE LATTER HAS BEEN ASSOCIATED WITH FRAILTY, MORBIDITY, AND MORTALITY IN ELDERLY SUBJECTS. HOWEVER, IT IS UNKNOWN TO WHAT EXTENT INFLAMMAGING OR LONGEVITY IS CONTROLLED BY EPIGENETIC EVENTS IN EARLY LIFE. TODAY, HUMAN DIET IS BELIEVED TO HAVE A MAJOR INFLUENCE ON BOTH THE DEVELOPMENT AND PREVENTION OF AGE-RELATED DISEASES. MOST PLANT-DERIVED DIETARY PHYTOCHEMICALS AND MACRO- AND MICRONUTRIENTS MODULATE OXIDATIVE STRESS AND INFLAMMATORY SIGNALING AND REGULATE METABOLIC PATHWAYS AND BIOENERGETICS THAT CAN BE TRANSLATED INTO STABLE EPIGENETIC PATTERNS OF GENE EXPRESSION. THEREFORE, DIET INTERVENTIONS DESIGNED FOR HEALTHY AGING HAVE BECOME A HOT TOPIC IN NUTRITIONAL EPIGENOMIC RESEARCH. INCREASING EVIDENCE HAS REVEALED THAT COMPLEX INTERACTIONS BETWEEN FOOD COMPONENTS AND HISTONE MODIFICATIONS, DNA METHYLATION, NON-CODING RNA EXPRESSION, AND CHROMATIN REMODELING FACTORS INFLUENCE THE INFLAMMAGING PHENOTYPE AND AS SUCH MAY PROTECT OR PREDISPOSE AN INDIVIDUAL TO MANY AGE-RELATED DISEASES. REMARKABLY, HUMANS PRESENT A BROAD RANGE OF RESPONSES TO SIMILAR DIETARY CHALLENGES DUE TO BOTH GENETIC AND EPIGENETIC MODULATIONS OF THE EXPRESSION OF TARGET PROTEINS AND KEY GENES INVOLVED IN THE METABOLISM AND DISTRIBUTION OF THE DIETARY CONSTITUENTS. HERE, WE WILL SUMMARIZE THE EPIGENETIC ACTIONS OF DIETARY COMPONENTS, INCLUDING PHYTOCHEMICALS, AND MACRO- AND MICRONUTRIENTS AS WELL AS METABOLITES, THAT CAN ATTENUATE INFLAMMAGING. WE WILL DISCUSS THE CHALLENGES FACING PERSONALIZED NUTRITION TO TRANSLATE HIGHLY VARIABLE INTERINDIVIDUAL EPIGENETIC DIET RESPONSES TO POTENTIAL INDIVIDUAL HEALTH BENEFITS/RISKS RELATED TO AGING DISEASE. 2015