1 4786 160 NUTRITION AND HEALTH DURING MID-LIFE: SEARCHING FOR SOLUTIONS AND MEETING CHALLENGES FOR THE AGING POPULATION. INTERACTIONS BETWEEN GENETIC (GENOME) AND ENVIRONMENTAL FACTORS (EPIGENOME) OPERATE DURING A PERSON'S ENTIRE LIFESPAN. THE AGING PROCESS IS ASSOCIATED WITH SEVERAL CELLULAR AND ORGANIC FUNCTIONAL ALTERATIONS THAT, AT THE END, CAUSE MULTI-ORGANIC CELL FAILURE. EPIGENETIC MECHANISMS OF AGING ARE MODIFIABLE BY APPROPRIATE PREVENTIVE ACTIONS MEDIATED BY SIRTUINS, CALORIC INPUT, DIET COMPONENTS, ADIPOSE TISSUE-RELATED INFLAMMATORY REACTIONS, AND PHYSICAL ACTIVITY. THE MEDITERRANEAN LIFESTYLE HAS BEEN FOR MANY MILLENNIA A DAILY HABIT FOR PEOPLE IN WESTERN CIVILIZATIONS LIVING AROUND THE MEDITERRANEAN SEA WHO WORKED INTENSIVELY AND SURVIVED WITH VERY FEW SEASONAL FOODS. A HIGH ADHERENCE TO THE TRADITIONAL MEDITERRANEAN DIET IS ASSOCIATED WITH LOW MORTALITY (HIGHER LONGEVITY) AND REDUCED RISK OF DEVELOPING CHRONIC DISEASES, INCLUDING CANCER, THE METABOLIC SYNDROME, DEPRESSION AND CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. REPORTS INDICATE THAT SOME DIETARY COMPONENTS, SUCH AS OLIVE OIL, ANTIOXIDANTS, OMEGA-3 AND -6 POLYUNSATURATED ACIDS, POLYPHENOLS AND FLAVONOIDS, MEDIATE BENEFICIAL ANTI-AGING EFFECTS (ANTI-CHRONIC DISEASES AND INCREASED LONGEVITY). EQUALLY, PHYSICAL ACTIVITY DISPLAYS A POSITIVE EFFECT, PRODUCING CALORIC CONSUMPTION AND REGULATION OF ADIPOSE AND PANCREATIC FUNCTION. THE PREDICTIVE STRENGTH OF SOME FOOD PATTERNS MAY BE A WAY OF DEVELOPING RECOMMENDATIONS FOR FOOD AND HEALTH POLICIES. THIS PAPER WILL DISCUSS SEVERAL WAYS OF IMPROVING HEALTH DURING MID-LIFE, FOCUSING ON CERTAIN GROUPS OF FUNCTIONAL FOODS AND HEALTHY HABITS WHICH MAY REDUCE OR PREVENT AGE-RELATED CHRONIC DISEASES. 2013 2 1394 46 DIET AND AGING. NUTRITION HAS IMPORTANT LONG-TERM CONSEQUENCES FOR HEALTH THAT ARE NOT ONLY LIMITED TO THE INDIVIDUAL BUT CAN BE PASSED ON TO THE NEXT GENERATION. IT CAN CONTRIBUTE TO THE DEVELOPMENT AND PROGRESSION OF CHRONIC DISEASES THUS EFFECTING LIFE SPAN. CALORIC RESTRICTION (CR) CAN EXTEND THE AVERAGE AND MAXIMUM LIFE SPAN AND DELAY THE ONSET OF AGE-ASSOCIATED CHANGES IN MANY ORGANISMS. CR ELICITS COORDINATED AND ADAPTIVE STRESS RESPONSES AT THE CELLULAR AND WHOLE-ORGANISM LEVEL BY MODULATING EPIGENETIC MECHANISMS (E.G., DNA METHYLATION, POSTTRANSLATIONAL HISTONE MODIFICATIONS), SIGNALING PATHWAYS THAT REGULATE CELL GROWTH AND AGING (E.G., TOR, AMPK, P53, AND FOXO), AND CELL-TO-CELL SIGNALING MOLECULES (E.G., ADIPONECTIN). THE OVERALL EFFECT OF THESE ADAPTIVE STRESS RESPONSES IS AN INCREASED RESISTANCE TO SUBSEQUENT STRESS, THUS DELAYING AGE-RELATED CHANGES AND PROMOTING LONGEVITY. IN HUMAN, CR COULD DELAY MANY DISEASES ASSOCIATED WITH AGING INCLUDING CANCER, DIABETES, ATHEROSCLEROSIS, CARDIOVASCULAR DISEASE, AND NEURODEGENERATIVE DISEASES. AS AN ALTERNATIVE TO CR, SEVERAL CR MIMETICS HAVE BEEN TESTED ON ANIMALS AND HUMANS. AT PRESENT, THE MOST PROMISING ALTERNATIVES TO THE USE OF CR IN HUMANS SEEM TO BE EXERCISE, ALONE OR IN COMBINATION WITH REDUCED CALORIE INTAKE, AND THE USE OF PLANT-DERIVED POLYPHENOL RESVERATROL AS A FOOD SUPPLEMENT. 2012 3 617 40 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 4 4597 30 NATURAL PRODUCTS WITH ANTI-AGING POTENTIAL: AFFECTED TARGETS AND MOLECULAR MECHANISMS. IN RECENT YEARS, THERE HAS BEEN A GREAT DEAL OF ATTENTION TOWARD THE MOLECULAR MACHINERY RELEVANT TO AGE-RELATED PROGRESSION CONTROLLED THROUGH THE EXTERNAL INTERVENTION OF POLYPHENOLS- AN EPIGENETIC-MODULATING DIET. NATURAL PRODUCTS MODULATE CELLULAR LONGEVITY THROUGH HISTONE POST-TRANSLATIONAL MODIFICATION AND CAN ALSO INDUCE THE UPREGULATION OF AUTOPHAGY, THUS REDUCING THE LEVEL OF ACETYL COENZYME A (ACCOA). IN ADDITION, THE EFFECT OF CALORIC RESTRICTION (CR) ON CANCER-RELATED CHRONIC INFLAMMATION IS OF GREAT SIGNIFICANCE IN AGING. IN LINE WITH THIS, SIRT1 PROTEIN LEVELS ARE EXPANDED IN RESPONSE TO CALORIE RESTRICTION MIMETICS (CRM), IN THIS WAY ACTING AS AUTOPHAGY INDUCERS RELEVANT TO CANCER PREVENTION. 2018 5 5986 34 TFEB IS A CENTRAL REGULATOR OF THE AGING PROCESS AND AGE-RELATED DISEASES. OLD AGE IS ASSOCIATED WITH A GREATER BURDEN OF DISEASE, INCLUDING NEURODEGENERATIVE DISORDERS SUCH AS ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE, AS WELL AS OTHER CHRONIC DISEASES. COINCIDENTALLY, POPULAR LIFESTYLE INTERVENTIONS, SUCH AS CALORIC RESTRICTION, INTERMITTENT FASTING, AND REGULAR EXERCISE, IN ADDITION TO PHARMACOLOGICAL INTERVENTIONS INTENDED TO PROTECT AGAINST AGE-RELATED DISEASES, INDUCE TRANSCRIPTION FACTOR EB (TFEB) AND AUTOPHAGY. IN THIS REVIEW, WE SUMMARIZE EMERGING DISCOVERIES THAT POINT TO TFEB ACTIVITY AFFECTING THE HALLMARKS OF AGING, INCLUDING INHIBITING DNA DAMAGE AND EPIGENETIC MODIFICATIONS, INDUCING AUTOPHAGY AND CELL CLEARANCE TO PROMOTE PROTEOSTASIS, REGULATING MITOCHONDRIAL QUALITY CONTROL, LINKING NUTRIENT-SENSING TO ENERGY METABOLISM, REGULATING PRO- AND ANTI-INFLAMMATORY PATHWAYS, INHIBITING SENESCENCE AND PROMOTING CELL REGENERATIVE CAPACITY. FURTHERMORE, THE THERAPEUTIC IMPACT OF TFEB ACTIVATION ON NORMAL AGING AND TISSUE-SPECIFIC DISEASE DEVELOPMENT IS ASSESSED IN THE CONTEXTS OF NEURODEGENERATION AND NEUROPLASTICITY, STEM CELL DIFFERENTIATION, IMMUNE RESPONSES, MUSCLE ENERGY ADAPTATION, ADIPOSE TISSUE BROWNING, HEPATIC FUNCTIONS, BONE REMODELING, AND CANCER. SAFE AND EFFECTIVE STRATEGIES OF ACTIVATING TFEB HOLD PROMISE AS A THERAPEUTIC STRATEGY FOR MULTIPLE AGE-ASSOCIATED DISEASES AND FOR EXTENDING LIFESPAN. 2023 6 4396 36 MODULATION OF CHRONIC INFLAMMATION BY QUERCETIN: THE BENEFICIAL EFFECTS ON OBESITY. OBESITY HAS BECOME A MAJOR RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. MOREOVER, OBESITY INDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE VASCULAR SYSTEM. QUERCETIN IS THE MAJOR REPRESENTATIVE OF THE FLAVONOID SUBCLASS OF FLAVONOLS, WHICH IS UBIQUITOUSLY CONTAINED WITHIN NATURAL PLANTS SUCH AS GREEN TEA, AND VEGETABLES, INCLUDING ONIONS AND APPLES. RESEARCHERS HAVE FOCUSED GREATER ATTENTION TO THE BENEFICIAL PHYSIOLOGICAL ROLES OF QUERCETIN, WHICH HAS ANTI-OXIDATIVE, ANTI-INFLAMMATORY, AND ANTI-FIBROTIC EFFECTS ON INSULIN RESISTANCE AND ATHEROSCLEROSIS IN OBESITY-RELATED DISEASES. ALSO, THE ANTI-INFLAMMATORY EFFECTS OF QUERCETIN ON INTESTINAL MICROBIOTA HAVE BEEN DEMONSTRATED IN OBESITY. IN ADDITION, THERE IS INCREASING EVIDENCE THAT QUERCETIN IS ASSOCIATED WITH EPIGENETIC ACTIVITIES IN CANCER, AND IN MATERNAL UNDERNUTRITION DURING GESTATION AND LACTATION. IN THIS REVIEW, WE FOCUS ON THE CHEMICAL PROPERTIES OF QUERCETIN, ITS DIETARY SOURCES IN OBESITY, AND ITS ANTI-INFLAMMATORY EFFECTS ON INSULIN RESISTANCE, ATHEROSCLEROSIS, INTESTINAL MICROBIOTA, AND MATERNAL UNDER-NUTRITION WITH EPIGENETIC ACTIVITY. 2020 7 4711 45 NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE CHILDREN AND ADOLESCENTS: A ROLE FOR NUTRITION? NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS BECOME THE MOST COMMON CAUSE OF CHRONIC LIVER DISEASE IN CHILDREN, PARALLELING THE INCREASING PREVALENCE OF OBESITY WORLDWIDE. THE PATHOGENESIS OF PAEDIATRIC NAFLD IS NOT FULLY UNDERSTOOD, BUT IT IS KNOWN THAT OBESITY, NUTRITION, LIFESTYLE VARIABLES, GENETIC AND EPIGENETIC FACTORS MAY BE CAUSALLY INVOLVED IN THE DEVELOPMENT OF THIS COMMON METABOLIC LIVER DISEASE. IN PARTICULAR, OBESITY AND NUTRITION ARE AMONG THE STRONGEST RISK FACTORS FOR PAEDIATRIC NAFLD, WHICH MAY EXERT THEIR ADVERSE HEPATIC EFFECTS ALREADY BEFORE BIRTH. EXCESS ENERGY INTAKE INDUCES HYPERTROPHY AND HYPERPLASIA OF ADIPOSE TISSUE WITH SUBSEQUENT DEVELOPMENT OF SYSTEMIC INSULIN RESISTANCE, WHICH IS ANOTHER IMPORTANT RISK FACTOR FOR NAFLD. DIET COMPOSITION AND IN PARTICULAR SIMPLE CARBOHYDRATE INTAKE (ESPECIALLY HIGH FRUCTOSE INTAKE) MAY PROMOTE THE DEVELOPMENT OF NAFLD, WHEREAS NON-DIGESTIBLE CARBOHYDRATES (DIETARY FIBER), BY AFFECTING GUT MICROBIOTA, MAY FAVOUR THE INTEGRITY OF GUT WALL AND REDUCE INFLAMMATION, OPPOSING THIS PROCESS. SATURATED FAT INTAKE MAY ALSO PROMOTE NAFLD DEVELOPMENT, WHEREAS UNSATURATED FAT INTAKE HAS SOME BENEFICIAL EFFECTS. PROTEIN INTAKE DOES NOT SEEM TO AFFECT THE DEVELOPMENT OF NAFLD, BUT FURTHER INVESTIGATION IS NEEDED. IN CONCLUSION, LIFESTYLE MODIFICATIONS TO INDUCE WEIGHT LOSS, THROUGH DIET AND PHYSICAL ACTIVITY, REMAIN THE MAINSTAY OF TREATMENT FOR PAEDIATRIC NAFLD. THE USE OF DIETARY SUPPLEMENTS, SUCH AS OMEGA-3 FATTY ACIDS AND PROBIOTICS, NEEDS FURTHER STUDY BEFORE RECOMMENDATION. 2022 8 4046 46 MADE IN THE WOMB: MATERNAL PROGRAMMING OF OFFSPRING CARDIOVASCULAR FUNCTION BY AN OBESOGENIC WOMB. OBESITY INCIDENCE HAS BEEN INCREASING AT AN ALARMING RATE, ESPECIALLY IN WOMEN OF REPRODUCTIVE AGE. IT IS ESTIMATED THAT 50% OF PREGNANCIES OCCUR IN OVERWEIGHT OR OBESE WOMEN. IT HAS BEEN DESCRIBED THAT MATERNAL OBESITY (MO) PREDISPOSES THE OFFSPRING TO AN INCREASED RISK OF DEVELOPING MANY CHRONIC DISEASES IN AN EARLY STAGE OF LIFE, INCLUDING OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE (CVD). CVD IS THE MAIN CAUSE OF DEATH WORLDWIDE AMONG MEN AND WOMEN, AND IT IS MANIFESTED IN A SEX-DIVERGENT WAY. MATERNAL NUTRITION AND MO DURING GESTATION COULD PROMPT CVD DEVELOPMENT IN THE OFFSPRING THROUGH ADAPTATIONS OF THE OFFSPRING'S CARDIOVASCULAR SYSTEM IN THE WOMB, INCLUDING CARDIAC EPIGENETIC AND PERSISTENT METABOLIC PROGRAMMING OF SIGNALING PATHWAYS AND MODULATION OF MITOCHONDRIAL METABOLIC FUNCTION. CURRENTLY, DESPITE DIET SUPPLEMENTATION, EFFECTIVE THERAPEUTICAL SOLUTIONS TO PREVENT THE DELETERIOUS CARDIAC OFFSPRING FUNCTION PROGRAMMING BY AN OBESOGENIC WOMB ARE LACKING. IN THIS REVIEW, WE DISCUSS THE MECHANISMS BY WHICH AN OBESOGENIC INTRAUTERINE ENVIRONMENT COULD PROGRAM THE OFFSPRING'S CARDIOVASCULAR METABOLISM IN A SEX-DIVERGENT WAY, WITH A SPECIAL FOCUS ON CARDIAC MITOCHONDRIAL FUNCTION, AND DEBATE POSSIBLE STRATEGIES TO IMPLEMENT DURING MO PREGNANCY THAT COULD AMELIORATE, REVERT, OR EVEN PREVENT DELETERIOUS EFFECTS OF MO ON THE OFFSPRING'S CARDIOVASCULAR SYSTEM. THE IMPACT OF MATERNAL PHYSICAL EXERCISE DURING AN OBESOGENIC PREGNANCY, NUTRITIONAL INTERVENTIONS, AND SUPPLEMENTATION ON OFFSPRING'S CARDIAC METABOLISM ARE DISCUSSED, HIGHLIGHTING CHANGES THAT MAY BE FAVORABLE TO MO OFFSPRING'S CARDIOVASCULAR HEALTH, WHICH MIGHT RESULT IN THE ATTENUATION OR EVEN PREVENTION OF THE DEVELOPMENT OF CVD IN MO OFFSPRING. THE OBJECTIVES OF THIS MANUSCRIPT ARE TO COMPREHENSIVELY EXAMINE THE VARIOUS ASPECTS OF MO DURING PREGNANCY AND EXPLORE THE UNDERLYING MECHANISMS THAT CONTRIBUTE TO AN INCREASED CVD RISK IN THE OFFSPRING. WE REVIEW THE CURRENT LITERATURE ON MO AND ITS IMPACT ON THE OFFSPRING'S CARDIOMETABOLIC HEALTH. FURTHERMORE, WE DISCUSS THE POTENTIAL LONG-TERM CONSEQUENCES FOR THE OFFSPRING. UNDERSTANDING THE MULTIFACETED EFFECTS OF MO ON THE OFFSPRING'S HEALTH IS CRUCIAL FOR HEALTHCARE PROVIDERS, RESEARCHERS, AND POLICYMAKERS TO DEVELOP EFFECTIVE STRATEGIES FOR PREVENTION AND INTERVENTION TO IMPROVE CARE. 2023 9 2424 40 EPIGENETIC SIGNATURES UNDERLYING INFLAMMATION: AN INTERPLAY OF NUTRITION, PHYSICAL ACTIVITY, METABOLIC DISEASES, AND ENVIRONMENTAL FACTORS FOR PERSONALIZED NUTRITION. AIM AND OBJECTIVE: EMERGING TRANSLATIONAL EVIDENCE SUGGESTS THAT EPIGENETIC ALTERATIONS (DNA METHYLATION, MIRNA EXPRESSION, AND HISTONE MODIFICATIONS) OCCUR AFTER EXTERNAL STIMULI AND MAY CONTRIBUTE TO EXACERBATED INFLAMMATION AND THE RISK OF SUFFERING SEVERAL DISEASES INCLUDING DIABETES, CARDIOVASCULAR DISEASES, CANCER, AND NEUROLOGICAL DISORDERS. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE ABOUT THE HARMFUL EFFECTS OF HIGH-FAT/HIGH-SUGAR DIETS, MICRONUTRIENT DEFICIENCIES (FOLATE, MANGANESE, AND CAROTENOIDS), OBESITY AND ASSOCIATED COMPLICATIONS, BACTERIAL/VIRAL INFECTIONS, SMOKING, EXCESSIVE ALCOHOL CONSUMPTION, SLEEP DEPRIVATION, CHRONIC STRESS, AIR POLLUTION, AND CHEMICAL EXPOSURE ON INFLAMMATION THROUGH EPIGENETIC MECHANISMS. ADDITIONALLY, THE EPIGENETIC PHENOMENA UNDERLYING THE ANTI-INFLAMMATORY POTENTIAL OF CALORIC RESTRICTION, N-3 PUFA, MEDITERRANEAN DIET, VITAMIN D, ZINC, POLYPHENOLS (I.E., RESVERATROL, GALLIC ACID, EPICATECHIN, LUTEOLIN, CURCUMIN), AND THE ROLE OF SYSTEMATIC EXERCISE ARE DISCUSSED. METHODS: ORIGINAL AND REVIEW ARTICLES ENCOMPASSING EPIGENETICS AND INFLAMMATION WERE SCREENED FROM MAJOR DATABASES (INCLUDING PUBMED, MEDLINE, SCIENCE DIRECT, SCOPUS, ETC.) AND ANALYZED FOR THE WRITING OF THE REVIEW PAPER. CONCLUSION: ALTHOUGH CAUTION SHOULD BE EXERCISED, RESEARCH ON EPIGENETIC MECHANISMS IS CONTRIBUTING TO UNDERSTAND PATHOLOGICAL PROCESSES INVOLVING INFLAMMATORY RESPONSES, THE PREDICTION OF DISEASE RISK BASED ON THE EPIGENOTYPE, AS WELL AS THE PUTATIVE DESIGN OF THERAPEUTIC INTERVENTIONS TARGETING THE EPIGENOME. 2021 10 5362 37 RECENT ADVANCES IN CALORIE RESTRICTION RESEARCH ON AGING. THE EXTENSION OF BOTH MEDIAN AND MAXIMUM LIFESPAN AND THE SUPPRESSION OF AGE-RELATED DISEASES IN LABORATORY ANIMALS BY REDUCED FOOD INTAKE, I.E., CALORIE RESTRICTION (CR) ARE REGARDED AS HALLMARKS OF CR'S ANTI-AGING ACTION. THE DIVERSE EFFICACY OF CR TO COUNTERACT AGING EFFECTS AND ITS EXPERIMENTAL REPRODUCIBILITY HAS MADE IT THE GOLD STANDARD OF MANY AGING INTERVENTION STUDIES OF RECENT YEARS. ALTHOUGH CR ORIGINALLY WAS USED AS A TOOL TO PERTURB THE AGING PROCESS OF LABORATORY ANIMALS AS TO UNCOVER CLUES OF UNDERLYING MECHANISMS OF AGING PROCESSES, CURRENT CR RESEARCH INTERESTS HAVE SHIFTED TO THE RETARDATION OF AGING-RELATED FUNCTIONAL DECLINE AND THE PREVENTION OF AGE-RELATED DISEASES. ADVANCES IN CR RESEARCH ON NON-HUMAN PRIMATES AND RECENT ENDEAVORS USING HUMAN SUBJECTS OFFER A PROMISING OUTLOOK FOR CR'S BENEFICIAL EFFECTS IN HEALTHY HUMAN AGING. IN THIS REVIEW, SEVERAL MAJOR ISSUES RELATED TO CR'S ANTI-AGING MECHANISMS ARE DISCUSSED BY HIGHLIGHTING THE IMPORTANCE OF MODULATING DELETERIOUS CHRONIC INFLAMMATION AT MOLECULAR LEVELS AND THE IMPACT OF EPIGENETIC CHROMATIN AND HISTONE MODIFICATIONS BY CR AT THE ULTIMATE CONTROL SITES OF GENE EXPRESSION. THE RECENT RESEARCH ON RAPAMYCIN AS A CR MIMETIC IS SUMMARIZED AND A BRIEF DESCRIPTION OF INTERMITTENT FEEDING PATTERNS IS REVIEWED IN COMPARISON TO THE CR EFFECT. 2013 11 5089 33 PLACENTAL ADAPTATIONS TO MICRONUTRIENT DYSREGULATION IN THE PROGRAMMING OF CHRONIC DISEASE. POOR NUTRITION DURING PREGNANCY IS KNOWN TO IMPAIR FOETAL DEVELOPMENT AND INCREASE THE RISK OF CHRONIC DISEASE IN OFFSPRING. BOTH MACRONUTRIENTS AND MICRONUTRIENTS ARE REQUIRED FOR A HEALTHY PREGNANCY ALTHOUGH SIGNIFICANTLY LESS IS UNDERSTOOD ABOUT THE ROLE OF MICRONUTRIENTS IN THE PROGRAMMING OF CHRONIC DISEASE. THIS IS DESPITE THE FACT THAT MODERN CALORIE RICH DIETS ARE OFTEN ALSO DEFICIENT IN KEY MICRONUTRIENTS. THE IMPORTANCE OF MICRONUTRIENTS IN GESTATIONAL DISORDERS IS CLEARLY UNDERSTOOD BUT HOW THEY IMPACT LONG TERM DISEASE IN HUMANS REQUIRES FURTHER INVESTIGATION. IN CONTRAST, ANIMAL STUDIES HAVE DEMONSTRATED HOW DIETS HIGH OR LOW IN SPECIFIC MICRONUTRIENTS INFLUENCE OFFSPRING PHYSIOLOGY. MANY OF THESE STUDIES HIGHLIGHT THE IMPORTANCE OF THE PLACENTA IN DETERMINING DISEASE RISK. THIS REVIEW WILL EXPLORE THE EFFECTS OF INDIVIDUAL VITAMINS, MINERALS AND TRACE ELEMENTS ON OFFSPRING DISEASE OUTCOMES AND DISCUSS SEVERAL KEY PLACENTAL ADAPTATIONS THAT ARE AFFECTED BY MULTIPLE MICRONUTRIENTS. THESE PLACENTAL ADAPTATIONS INCLUDE MICRONUTRIENT INDUCED DYSREGULATION OF OXIDATIVE STRESS, ALTERED METHYL DONOR AVAILABILITY AND ITS IMPACT ON EPIGENETIC MECHANISMS AS WELL AS ENDOCRINE DYSFUNCTION. CRITICAL GAPS IN OUR CURRENT KNOWLEDGE AND THE RELATIVE IMPORTANCE OF DIFFERENT MICRONUTRIENTS AT DIFFERENT GESTATIONAL AGES WILL ALSO BE HIGHLIGHTED. FINALLY, THIS REVIEW WILL DISCUSS THE NEED FOR FURTHER STUDIES TO CHARACTERISE THE MICRONUTRIENT STATUS OF AUSTRALIAN WOMEN OF REPRODUCTIVE AGE AND CORRELATE MICRONUTRIENT STATUS TO PLACENTAL ADAPTATIONS, PREGNANCY COMPLICATIONS AND OFFSPRING DISEASE. 2018 12 3578 36 IMPACT OF PARENTAL OVER- AND UNDERWEIGHT ON THE HEALTH OF OFFSPRING. PARENTAL EXCESS WEIGHT AND ESPECIALLY PREGESTATIONAL MATERNAL OBESITY AND EXCESSIVE WEIGHT GAIN DURING PREGNANCY HAVE BEEN RELATED TO AN INCREASED RISK OF METABOLIC (OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, METABOLIC SYNDROME) AND NONMETABOLIC (CANCER, OSTEOPOROSIS, ASTHMA, NEUROLOGIC ALTERATIONS) DISEASES IN THE OFFSPRING, PROBABLY MEDIATED BY EPIGENETIC MECHANISMS OF FETAL PROGRAMMING. MATERNAL UNDERWEIGHT IS LESS COMMON IN DEVELOPED SOCIETIES, BUT THE DISCREPANCY BETWEEN A POOR NUTRITIONAL ENVIRONMENT IN UTERO AND A NORMAL OR EXCESSIVE POSTNATAL FOOD SUPPLY WITH RAPID GROWTH CATCH-UP APPEARS TO BE THE MAIN CANDIDATE MECHANISM OF THE DEVELOPMENT OF CHRONIC DISEASES DURING THE OFFSPRING'S ADULTHOOD. THE ROLE OF THE POSTNATAL ENVIRONMENT IN BOTH SCENARIOS (PARENTAL OVERWEIGHT OR UNDERWEIGHT) ALSO SEEMS TO INFLUENCE THE OFFSPRING'S HEALTH. LIFESTYLE INTERVENTIONS BEFORE AND DURING PREGNANCY IN BOTH PARENTS, BUT ESPECIALLY IN THE MOTHER, AS WELL AS IN CHILDREN AFTER BIRTH, ARE ADVISABLE TO COUNTERACT THE MANY UNDESIRABLE CHRONIC CONDITIONS DESCRIBED. 2019 13 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 14 1153 32 CONSEQUENCES OF PATERNAL NUTRITION ON OFFSPRING HEALTH AND DISEASE. IT IS WELL ESTABLISHED THAT THE MATERNAL DIET DURING THE PERICONCEPTIONAL PERIOD AFFECTS THE PROGENY'S HEALTH. A GROWING BODY OF EVIDENCE SUGGESTS THAT THE PATERNAL DIET ALSO INFLUENCES DISEASE ONSET IN OFFSPRING. FOR MANY YEARS, SPERM WAS CONSIDERED ONLY TO CONTRIBUTE HALF OF THE PROGENY'S GENOME. IT NOW APPEARS THAT IT ALSO PLAYS A CRUCIAL ROLE IN HEALTH AND DISEASE IN OFFSPRING'S ADULT LIFE. THE NUTRITIONAL STATUS AND ENVIRONMENTAL EXPOSURE OF FATHERS DURING THEIR CHILDHOOD AND/OR THE PERICONCEPTIONAL PERIOD HAVE SIGNIFICANT TRANSGENERATIONAL CONSEQUENCES. THIS REVIEW AIMS TO DESCRIBE THE EFFECTS OF VARIOUS HUMAN AND RODENT PATERNAL FEEDING PATTERNS ON PROGENY'S METABOLISM AND HEALTH, INCLUDING FASTING OR INTERMITTENT FASTING, LOW-PROTEIN AND FOLIC ACID DEFICIENT FOOD, AND OVERNUTRITION IN HIGH-FAT AND HIGH-SUGAR DIETS. THE IMPACT ON PREGNANCY OUTCOME, METABOLIC PATHWAYS, AND CHRONIC DISEASE ONSET WILL BE DESCRIBED. THE BIOLOGICAL AND EPIGENETIC MECHANISMS UNDERLYING THE TRANSMISSION FROM FATHERS TO THEIR PROGENY WILL BE DISCUSSED. ALL THESE DATA PROVIDE EVIDENCE OF THE IMPACT OF PATERNAL NUTRITION ON PROGENY HEALTH WHICH COULD LEAD TO PREVENTIVE DIET RECOMMENDATIONS FOR FUTURE FATHERS. 2021 15 6732 26 WESTERN DIET AND THE IMMUNE SYSTEM: AN INFLAMMATORY CONNECTION. THE CONSUMPTION OF WESTERN-TYPE CALORICALLY RICH DIETS COMBINED WITH CHRONIC OVERNUTRITION AND A SEDENTARY LIFESTYLE IN WESTERN SOCIETIES EVOKES A STATE OF CHRONIC METABOLIC INFLAMMATION, TERMED METAFLAMMATION. METAFLAMMATION CONTRIBUTES TO THE DEVELOPMENT OF MANY PREVALENT NON-COMMUNICABLE DISEASES (NCDS), AND THESE LIFESTYLE-ASSOCIATED PATHOLOGIES REPRESENT A RISING PUBLIC HEALTH PROBLEM WITH GLOBAL EPIDEMIC DIMENSIONS. A BETTER UNDERSTANDING OF HOW MODERN LIFESTYLE AND WESTERN DIET (WD) ACTIVATE IMMUNE CELLS IS ESSENTIAL FOR THE DEVELOPMENT OF EFFICIENT PREVENTIVE AND THERAPEUTIC STRATEGIES FOR COMMON NCDS. HERE, WE REVIEW THE CURRENT MECHANISTIC UNDERSTANDING OF HOW THE WESTERN LIFESTYLE CAN INDUCE METAFLAMMATION, AND WE DISCUSS HOW THIS KNOWLEDGE CAN BE TRANSLATED TO PROTECT THE PUBLIC FROM THE HEALTH BURDEN ASSOCIATED WITH THEIR SELECTED LIFESTYLE. 2019 16 4895 35 OXIDATIVE STRESS DRIVERS AND MODULATORS IN OBESITY AND CARDIOVASCULAR DISEASE: FROM BIOMARKERS TO THERAPEUTIC APPROACH. THIS REVIEW ARTICLE IS INTENDED TO DESCRIBE HOW OXIDATIVE STRESS REGULATES CARDIOVASCULAR DISEASE DEVELOPMENT AND PROGRESSION. EPIGENETIC MECHANISMS RELATED TO OXIDATIVE STRESS, AS WELL AS MORE RELIABLE BIOMARKERS OF OXIDATIVE STRESS, ARE EMERGING OVER THE LAST YEARS AS POTENTIALLY USEFUL TOOLS TO DESIGN THERAPEUTIC APPROACHES AIMED AT MODULATING ENHANCED OXIDATIVE STRESS "IN VIVO", THEREBY MITIGATING THE CONSEQUENT ATHEROSCLEROTIC BURDEN. AS A PARADIGM, WE DESCRIBE THE CASE OF OBESITY, IN WHICH THE INTERTWINING AMONG OXIDATIVE STRESS, DUE TO CALORIC OVERLOAD, CHRONIC LOW-GRADE INFLAMMATION INDUCED BY ADIPOSE TISSUE DYSFUNCTION, AND PLATELET ACTIVATION REPRESENTS A VICIOUS CYCLE FAVORING THE PROGRESSION OF ATHEROTHROMBOSIS. OXIDATIVE STRESS IS A MAJOR PLAYER IN THE PATHOBIOLOGY OF CARDIOVASCULAR DISEASE (CVD). REACTIVE OXYGEN SPECIES (ROS)- DEPENDENT SIGNALING PATHWAYS PROMPT TRANSCRIPTIONAL AND EPIGENETIC DYSREGULATION, INDUCING CHRONIC LOW-GRADE INFLAMMATION, PLATELET ACTIVATION AND ENDOTHELIAL DYSFUNCTION. IN ADDITION, SEVERAL OXIDATIVE BIOMARKERS HAVE BEEN PROPOSED WITH THE POTENTIAL TO IMPROVE CURRENT UNDERSTANDING OF THE MECHANISMS UNDERLYING CVD. THESE INCLUDE ROS-GENERATING AND/OR QUENCHING MOLECULES, AND ROS-MODIFIED COMPOUNDS, SUCH AS F2-ISOPROSTANES. THERE IS ALSO INCREASING EVIDENCE THAT NONCODING MICRO- RNA (MI-RNA) ARE CRITICALLY INVOLVED IN POST- TRANSCRIPTIONAL REGULATION OF CELL FUNCTIONS, INCLUDING ROS GENERATION, INFLAMMATION, REGULATION OF CELL PROLIFERATION, ADIPOCYTE DIFFERENTIATION, ANGIOGENESIS AND APOPTOSIS. THESE MOLECULES HAVE PROMISING TRANSLATIONAL POTENTIAL AS BOTH MARKERS OF DISEASE AND SITE OF TARGETED INTERVENTIONS. FINALLY, OXIDATIVE STRESS IS A CRITICAL TARGET OF SEVERAL CARDIOPROTECTIVE DRUGS AND NUTRACEUTICALS, INCLUDING ANTIDIABETIC AGENTS, STATINS, RENIN-ANGIOTENSIN SYSTEM BLOCKERS, POLYPHENOLS AND OTHER ANTIOXIDANTS. FURTHER UNDERSTANDING OF ROS-GENERATING MECHANISMS, THEIR BIOLOGICAL ROLE AS WELL AS POTENTIAL THERAPEUTIC IMPLICATIONS WOULD TRANSLATE INTO CONSISTENT BENEFITS FOR EFFECTIVE CV PREVENTION. 2015 17 2699 37 EXCESS BODY WEIGHT: NOVEL INSIGHTS INTO ITS ROLES IN OBESITY COMORBIDITIES. EXCESS BODY WEIGHT IS A GLOBAL HEALTH PROBLEM DUE TO SEDENTARY LIFESTYLE AND UNHEALTHY DIET, AFFECTING 2 BILLION POPULATION WORLDWIDE. OBESITY IS A MAJOR RISK FACTOR FOR METABOLIC DISEASES. NOTABLY, THE METABOLIC RISK OF OBESITY LARGELY DEPENDS ON BODY WEIGHT DISTRIBUTION, OF WHICH VISCERAL ADIPOSE TISSUES BUT NOT SUBCUTANEOUS FATS ARE CLOSELY ASSOCIATED WITH OBESITY COMORBIDITIES, INCLUDING TYPE 2 DIABETES, NON-ALCOHOLIC FATTY LIVER DISEASE, CARDIOVASCULAR DISEASE AND CERTAIN TYPES OF CANCER. LATEST MULTI-OMICS AND MECHANISTICAL STUDIES REPORTED THE CRUCIAL INVOLVEMENT OF GENETIC AND EPIGENETIC ALTERATIONS, ADIPOKINES DYSREGULATION, IMMUNITY CHANGES, IMBALANCE OF WHITE AND BROWN ADIPOSE TISSUES, AND GUT MICROBIAL DYSBIOSIS IN MEDIATING THE PATHOGENIC ASSOCIATION BETWEEN VISCERAL ADIPOSE TISSUES AND COMORBIDITIES. IN THIS REVIEW, WE EXPLORE THE EPIDEMIOLOGY OF EXCESS BODY WEIGHT AND THE UP-TO-DATE MECHANISM OF HOW EXCESS BODY WEIGHT AND OBESITY LEAD TO CHRONIC COMPLICATIONS. WE ALSO EXAMINE THE UTILIZATION OF VISCERAL FAT MEASUREMENT AS AN ACCURATE CLINICAL PARAMETER FOR RISK ASSESSMENT IN HEALTHY INDIVIDUALS AND CLINICAL OUTCOME PREDICTION IN OBESE SUBJECTS. IN ADDITION, CURRENT APPROACHES FOR THE PREVENTION AND TREATMENT OF EXCESS BODY WEIGHT AND ITS RELATED METABOLIC COMORBIDITIES ARE FURTHER DISCUSSED. 2023 18 4795 37 NUTRITIONAL GENOMICS IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A COMMON CHRONIC CONDITION ASSOCIATED WITH GENETIC AND ENVIRONMENTAL FACTORS IN WHICH FAT ABNORMALLY ACCUMULATES IN THE LIVER. NAFLD IS EPIDEMIOLOGICALLY ASSOCIATED WITH OBESITY, TYPE 2 DIABETES, AND DYSLIPIDEMIA. ENVIRONMENTAL FACTORS, SUCH AS PHYSICAL INACTIVITY AND AN UNBALANCED DIET, INTERACT WITH GENETIC FACTORS, SUCH AS EPIGENETIC MECHANISMS AND POLYMORPHISMS FOR THE GENESIS AND DEVELOPMENT OF THE CONDITION. DIFFERENT GENETIC POLYMORPHISMS SEEM TO BE INVOLVED IN THIS CONTEXT, INCLUDING VARIANTS IN PNPLA3, TM6SF2, PEMT, AND CHDH GENES, PLAYING A ROLE IN THE DISEASE'S SUSCEPTIBILITY, DEVELOPMENT, AND SEVERITY. FROM CARBOHYDRATE INTAKE AND WEIGHT LOSS TO OMEGA-3 SUPPLEMENTATION AND CALORIC RESTRICTION, DIFFERENT DIETARY AND NUTRITIONAL FACTORS APPEAR TO BE INVOLVED IN CONTROLLING THE ONSET AND PROGRESSION OF NAFLD CONDITIONS INFLUENCING METABOLISM, GENE, AND PROTEIN EXPRESSION. THE POLYGENIC RISK SCORE REPRESENTS A SUM OF TRAIT-ASSOCIATED ALLELES CARRIED BY AN INDIVIDUAL AND SEEMS TO BE ASSOCIATED WITH NAFLD OUTCOMES DEPENDING ON THE DIETARY CONTEXT. UNDERSTANDING THE EXACT EXTENT TO WHICH LIFESTYLE INTERVENTIONS AND GENETIC PREDISPOSITIONS CAN PLAY A ROLE IN THE PREVENTION AND MANAGEMENT OF NAFLD CAN BE CRUCIAL FOR THE ESTABLISHMENT OF A PERSONALIZED AND INTEGRATIVE APPROACH TO PATIENTS. 2023 19 140 29 ABERRANT DNA METHYLATION MEDIATES THE TRANSGENERATIONAL RISK OF METABOLIC AND CHRONIC DISEASE DUE TO MATERNAL OBESITY AND OVERNUTRITION. MATERNAL OBESITY IS A RAPIDLY EVOLVING UNIVERSAL EPIDEMIC LEADING TO ACUTE AND LONG-TERM MEDICAL AND OBSTETRIC HEALTH ISSUES, INCLUDING INCREASED MATERNAL RISKS OF GESTATIONAL DIABETES, HYPERTENSION AND PRE-ECLAMPSIA, AND THE FUTURE RISKS FOR OFFSPRING'S PREDISPOSITION TO METABOLIC DISEASES. EPIGENETIC MODIFICATION, IN PARTICULAR DNA METHYLATION, REPRESENTS A MECHANISM WHEREBY ENVIRONMENTAL EFFECTS IMPACT ON THE PHENOTYPIC EXPRESSION OF HUMAN DISEASE. MATERNAL OBESITY OR OVERNUTRITION CONTRIBUTES TO THE ALTERATIONS IN DNA METHYLATION DURING EARLY LIFE WHICH, THROUGH FETAL PROGRAMMING, CAN PREDISPOSE THE OFFSPRING TO MANY METABOLIC AND CHRONIC DISEASES, SUCH AS NON-ALCOHOLIC FATTY LIVER DISEASE, OBESITY, DIABETES, AND CHRONIC KIDNEY DISEASE. THIS REVIEW AIMS TO SUMMARIZE FINDINGS FROM HUMAN AND ANIMAL STUDIES, WHICH SUPPORT THE ROLE OF MATERNAL OBESITY IN FETAL PROGRAMING AND THE POTENTIAL BENEFIT OF ALTERING DNA METHYLATION TO LIMIT MATERNAL OBESITY RELATED DISEASE IN THE OFFSPRING. 2021 20 1411 39 DIETARY NATURAL PRODUCTS AS EPIGENETIC MODIFIERS IN AGING-ASSOCIATED INFLAMMATION AND DISEASE. COVERING: UP TO 2020CHRONIC, LOW-GRADE INFLAMMATION IS LINKED TO AGING AND HAS BEEN TERMED "INFLAMMAGING". INFLAMMAGING IS CONSIDERED A KEY CONTRIBUTOR TO THE DEVELOPMENT OF METABOLIC DYSFUNCTION AND A BROAD SPECTRUM OF DISEASES OR DISORDERS INCLUDING DECLINES IN BRAIN AND HEART FUNCTION. GENOME-WIDE ASSOCIATION STUDIES (GWAS) COUPLED WITH EPIGENOME-WIDE ASSOCIATION STUDIES (EWAS) HAVE SHOWN THE IMPORTANCE OF DIET IN THE DEVELOPMENT OF CHRONIC AND AGE-RELATED DISEASES. MOREOVER, DIETARY INTERVENTIONS E.G. CALORIC RESTRICTION CAN ATTENUATE INFLAMMATION TO DELAY AND/OR PREVENT THESE DISEASES. COMMON THEMES IN THESE STUDIES ENTAIL THE USE OF PHYTOCHEMICALS (PLANT-DERIVED COMPOUNDS) OR THE PRODUCTION OF SHORT CHAIN FATTY ACIDS (SCFAS) AS EPIGENETIC MODIFIERS OF DNA AND HISTONE PROTEINS. EPIGENETIC MODIFICATIONS ARE DYNAMICALLY REGULATED AND AS SUCH, SERVE AS POTENTIAL THERAPEUTIC TARGETS FOR THE TREATMENT OR PREVENTION OF AGE-RELATED DISEASE. IN THIS REVIEW, WE WILL FOCUS ON THE ROLE FOR NATURAL PRODUCTS THAT INCLUDE PHYTOCHEMICALS AND SHORT CHAIN FATTY ACIDS (SCFAS) AS REGULATORS OF THESE EPIGENETIC ADAPTATIONS. SPECIFICALLY, WE DISCUSS REGULATORS OF METHYLATION, ACETYLATION AND ACYLATION, IN THE PROTECTION FROM CHRONIC INFLAMMATION DRIVEN METABOLIC DYSFUNCTION AND DETERIORATION OF NEUROCOGNITIVE AND CARDIAC FUNCTION. 2020