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 2855 60 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 3 6346 38 THE ROLE OF EPIGENETICS IN CARDIOVASCULAR HEALTH AND AGEING: A FOCUS ON PHYSICAL ACTIVITY AND NUTRITION. THE CARDIOVASCULAR SYSTEM IS RESPONSIBLE FOR TRANSPORT OF BLOOD AND NUTRIENTS TO TISSUES, AND IS PIVOTAL TO THE PHYSIOLOGICAL HEALTH AND LONGEVITY. EPIGENETIC MODIFICATION IS A NATURAL, AGE-ASSOCIATED PROCESS RESULTING IN HIGHLY CONTEXTUALISED GENE EXPRESSION WITH CLEAR IMPLICATIONS FOR CELL DIFFERENTIATION AND DISEASE ONSET. BIOLOGICAL/EPIGENETIC AGE IS INDEPENDENT OF CHRONOLOGICAL AGE, CONSTITUTING A HIGHLY REFLECTIVE SNAPSHOT OF AN INDIVIDUAL'S OVERALL HEALTH. ACCELERATED VASCULAR AGEING IS OF MAJOR CONCERN, EFFECTIVELY LOWERING DISEASE THRESHOLD. AGE-RELATED CHRONIC ILLNESS INVOLVES A COMPLEX INTERPLAY BETWEEN MANY BIOLOGICAL PROCESSES AND IS MODULATED BY NON-MODIFIABLE AND MODIFIABLE RISK FACTORS. THESE ALTER THE STATIC GENOME BY A NUMBER OF EPIGENETIC MECHANISMS, WHICH CHANGE GENE EXPRESSION IN AN AGE AND LIFESTYLE DEPENDENT MANNER. THIS 'EPIGENETIC DRIFT' IMPACTS HEALTH AND CONTRIBUTES TO THE ETIOLOGY OF CHRONIC ILLNESS. LIFESTYLE FACTORS MAY CAUSE ACCELERATION OF THIS EPIGENETIC "CLOCK", PRE-DISPOSING INDIVIDUALS TO CARDIOVASCULAR DISEASE. NUTRITION AND PHYSICAL ACTIVITY ARE MODIFIABLE LIFESTYLE CHOICES, SYNERGISTICALLY CONTRIBUTING TO CARDIOVASCULAR HEALTH. THEY REPRESENT A POWERFUL POTENTIAL EPIGENETIC INTERVENTION POINT FOR EFFECTIVE CARDIOVASCULAR PROTECTIVE AND MANAGEMENT STRATEGIES. THUS, TOGETHER WITH TRADITIONAL RISK FACTORS, MONITORING THE EPIGENETIC SIGNATURE OF AGEING MAY PROVE BENEFICIAL FOR TAILORING LIFESTYLE TO FIT BIOLOGY - SUPPORTING THE INCREASINGLY POPULAR CONCEPT OF "AGEING WELL". 2018 4 3577 57 IMPACT OF NUTRITION ON TELOMERE HEALTH: SYSTEMATIC REVIEW OF OBSERVATIONAL COHORT STUDIES AND RANDOMIZED CLINICAL TRIALS. DIET, PHYSICAL ACTIVITY, AND OTHER LIFESTYLE FACTORS HAVE BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF SEVERAL CHRONIC DISEASES, BUT ALSO IN A LOWER TOTAL MORTALITY AND LONGER LIFE EXPECTANCY. ONE OF THE MECHANISMS IN WHICH DIET CAN REDUCE THE RISK OF DISEASE IS WITH REGARD TO ITS IMPACT ON TELOMERES. TELOMERE LENGTH (TL) IS HIGHLY CORRELATED TO CHRONOLOGICAL AGE AND METABOLIC STATUS. INDIVIDUALS WITH SHORTER TELOMERES ARE AT HIGHER RISK OF CHRONIC DISEASES AND MORTALITY. DIET MAY INFLUENCE TL BY SEVERAL MECHANISMS SUCH AS REGULATING OXIDATIVE STRESS AND INFLAMMATION OR MODULATING EPIGENETIC REACTIONS. THE PRESENT SYSTEMATIC REVIEW AIMS TO EXAMINE THE RESULTS FROM EPIDEMIOLOGIC AND CLINICAL TRIALS CONDUCTED IN HUMANS EVALUATING THE ROLE OF NUTRIENTS, FOOD GROUPS, AND DIETARY PATTERNS ON TL. WE ALSO DISCUSS THE POSSIBLE MECHANISMS OF ACTION THAT INFLUENCE THIS PROCESS, WITH THE PERSPECTIVE THAT TL COULD BE A NOVEL BIOMARKER INDICATING THE RISK OF METABOLIC DISTURBANCES AND AGE-RELATED DISEASES. THE AVAILABLE EVIDENCE SUGGESTS THAT SOME ANTIOXIDANT NUTRIENTS, THE CONSUMPTION OF FRUITS AND VEGETABLES, AND MEDITERRANEAN DIET ARE MAINLY ASSOCIATED WITH LONGER TELOMERES. HOWEVER, MOST OF THE EVIDENCE IS BASED ON HIGH HETEROGENIC OBSERVATIONAL STUDIES AND VERY FEW RANDOMIZED CLINICAL TRIALS (RCTS). THEREFORE, THE ASSOCIATIONS SUMMARIZED IN THE PRESENT REVIEW NEED TO BE CONFIRMED WITH LARGER PROSPECTIVE COHORT STUDIES AND BETTER-DESIGNED RCTS. 2020 5 4796 38 NUTRITIONAL INTERVENTION AS AN ESSENTIAL PART OF MULTIPLE SCLEROSIS TREATMENT? MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. IN ADDITION TO THE GENETIC, EPIGENETIC AND IMMUNOLOGICAL COMPONENTS, VARIOUS OTHER FACTORS, E.G. UNHEALTHY DIETARY HABITS, PLAY A ROLE IN THE MS PATHOGENESIS. DIETARY INTERVENTION IS A HIGHLY APPEALING APPROACH, AS IT PRESENTS A SIMPLE AND RELATIVELY LOW RISK METHOD TO POTENTIALLY IMPROVE OUTCOMES IN PATIENTS WITH BRAIN DISORDERS IN ORDER TO ACHIEVE REMISSION AND IMPROVEMENT OF CLINICAL STATUS, WELL-BEING AND LIFE EXPECTANCY OF PATIENTS WITH MS. THE IMPORTANCE OF SATURATED FAT INTAKE RESTRICTION FOR THE CLINICAL STATUS IMPROVEMENT OF MS PATIENTS WAS POINTED FOR THE FIRST TIME IN 1950S. RECENTLY, DECREASED RISK OF FIRST CLINICAL DIAGNOSIS OF CNS DEMYELINATION ASSOCIATED WITH HIGHER INTAKE OF OMEGA-3 POLYUNSATURATED FATTY ACIDS PARTICULARLY ORIGINATING FROM FISH WAS REPORTED. ONLY FEW CLINICAL TRIALS HAVE BEEN PERFORMED TO ADDRESS THE QUESTION OF THE ROLE OF DIETARY INTERVENTION, SUCH IS E.G. LOW SATURATED FAT DIET IN MS TREATMENT. THIS REVIEW SUMMARIZES CURRENT KNOWLEDGE ABOUT THE EFFECT OF DIFFERENT DIETARY APPROACHES (DIETS LOW IN SATURATED FAT AND DIETARY SUPPLEMENTS SUCH AS FISH OIL, LIPOIC ACID, OMEGA-3 POLYUNSATURATED FATTY ACIDS, SEEDS OILS, HIGH FIBER DIET, VITAMIN D, ETC.) ON NEUROLOGICAL SIGNS, PATIENT'S WELL-BEING, PHYSICAL AND INFLAMMATORY STATUS. SO FAR THE RESULTS ARE NOT CONCLUSIVE, THEREFORE MUCH MORE RESEARCH IS NEEDED TO CONFIRM AND TO UNDERSTAND THE EFFECTIVENESS OF THESE DIETARY INTERVENTIONS IN THE LONG TERM AND WELL DEFINED STUDIES. 2018 6 2881 34 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS. 2015 7 6109 37 THE EPIGENETIC AGING, OBESITY, AND LIFESTYLE. THE PREVALENCE OF OBESITY HAS DRAMATICALLY INCREASED WORLDWIDE OVER THE PAST DECADES. AGING-RELATED CHRONIC CONDITIONS, SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, ARE MORE PREVALENT IN INDIVIDUALS WITH OBESITY, THUS REDUCING THEIR LIFESPAN. EPIGENETIC CLOCKS, THE NEW METRICS OF BIOLOGICAL AGE BASED ON DNA METHYLATION PATTERNS, COULD BE CONSIDERED A REFLECTION OF THE STATE OF ONE'S HEALTH. SEVERAL ENVIRONMENTAL EXPOSURES AND LIFESTYLE FACTORS CAN INDUCE EPIGENETIC AGING ACCELERATIONS, INCLUDING OBESITY, THUS LEADING TO AN INCREASED RISK OF AGE-RELATED DISEASES. THE INSIGHT INTO THE COMPLEX LINK BETWEEN OBESITY AND AGING MIGHT HAVE SIGNIFICANT IMPLICATIONS FOR THE PROMOTION OF HEALTH AND THE MITIGATION OF FUTURE DISEASE RISK. THE PRESENT NARRATIVE REVIEW TAKES INTO ACCOUNT THE INTERACTION BETWEEN EPIGENETIC AGING AND OBESITY, SUGGESTING THAT EPIGENOME MAY BE AN INTRIGUING TARGET FOR AGE-RELATED PHYSIOLOGICAL CHANGES AND THAT ITS MODIFICATION COULD INFLUENCE AGING AND PROLONG A HEALTHY LIFESPAN. THEREFORE, WE HAVE FOCUSED ON DNA METHYLATION AGE AS A CLINICAL BIOMARKER, AS WELL AS ON THE POTENTIAL REVERSAL OF EPIGENETIC AGE USING A PERSONALIZED DIET- AND LIFESTYLE-BASED INTERVENTION. 2022 8 2226 40 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 9 625 40 BIOLOGICAL AGE AND ENVIRONMENTAL RISK FACTORS FOR DEMENTIA AND STROKE: MOLECULAR MECHANISMS. SINCE THE DEVELOPMENT OF ANTIBIOTICS AND VACCINATION, AS WELL AS MAJOR IMPROVEMENTS IN PUBLIC HYGIENE, THE MAIN RISK FACTORS FOR MORBIDITY AND MORTALITY ARE AGE AND CHRONIC EXPOSURE TO ENVIRONMENTAL FACTORS, BOTH OF WHICH CAN INTERACT WITH GENETIC PREDISPOSITIONS. AS THE AVERAGE AGE OF THE POPULATION INCREASES, THE PREVALENCE AND COSTS OF CHRONIC DISEASES, ESPECIALLY NEUROLOGICAL CONDITIONS, ARE RAPIDLY INCREASING. THE DELETERIOUS EFFECTS OF AGE AND ENVIRONMENTAL RISK FACTORS, DEVELOP CHRONICALLY OVER RELATIVELY LONG PERIODS OF TIME, IN CONTRAST TO THE RELATIVELY RAPID DELETERIOUS EFFECTS OF INFECTIOUS DISEASES OR ACCIDENTS. OF PARTICULAR INTEREST IS THE HYPOTHESIS THAT THE DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS MAY BE MEDIATED BY ACCELERATION OF BIOLOGICAL AGE. THIS HYPOTHESIS IS SUPPORTED BY EVIDENCE THAT DIETARY RESTRICTION, WHICH UNIVERSALLY DELAYS AGE-RELATED DISEASES, ALSO AMELIORATES DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS. CONVERSELY, BOTH AGE AND ENVIRONMENTAL RISK FACTORS ARE ASSOCIATED WITH THE ACCUMULATION OF SOMATIC MUTATIONS IN MITOTIC CELLS AND EPIGENETIC MODIFICATIONS THAT ARE A MEASURE OF "BIOLOGICAL AGE", A BETTER PREDICTOR OF AGE-RELATED MORBIDITY AND MORTALITY THAN CHRONOLOGICAL AGE. HERE WE REVIEW EVIDENCE THAT ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING AND AIR POLLUTION MAY ALSO DRIVE NEUROLOGICAL CONDITIONS, INCLUDING ALZHEIMER'S DISEASE, BY THE ACCELERATION OF BIOLOGICAL AGE, MEDIATED BY CUMULATIVE AND PERSISTENT EPIGENETIC EFFECTS AS WELL AS SOMATIC MUTATIONS. ELUCIDATION OF SUCH MECHANISMS COULD PLAUSIBLY ALLOW THE DEVELOPMENT OF INTERVENTIONS WHICH DELAY DELETERIOUS EFFECTS OF BOTH AGING AND ENVIRONMENTAL RISK FACTORS. 2022 10 3546 44 IMMUNOMODULATORY DIET IN PEDIATRIC AGE. IN THE LAST FEW DECADES, THE IMPORTANCE OF A FUNCTIONING IMMUNE SYSTEM AND HEALTH STATUS HAS BECOME MORE EVIDENT. MULTIPLE FACTORS ARE ABLE TO INFLUENCE THE DEVELOPMENT OF CHRONIC DISEASES AND DIET IS ONE OF THE MOST IMPORTANT ENVIRONMENTAL FACTORS. EVIDENCE DEMONSTRATES THAT DIETARY PATTERNS HIGH IN FAT AND LOW IN FIBER ARE ASSOCIATED WITH THE DEVELOPMENT OF NON-COMMUNICABLE DISEASES. MOREOVER, OPTIMAL NUTRITIONAL STATUS CAN MODULATE IMMUNE MATURATION AND RESPONSE TO INFLAMMATION. DURING INFLAMMATORY CONDITIONS, NUTRITIONAL DEFICIENCIES MAY OCCUR, ESTABLISHING A VICIOUS CIRCLE, CONSEQUENTLY A BALANCED NUTRITIONAL STATUS IS ESSENTIAL TO PREVENT AND COUNTERACT INFECTIONS. DIETARY DIVERSITY CAN PREVENT ALLERGIC DISEASES AND NUTRIENTS SUCH AS DHA, ARGININE, VITAMINS AND TRACE ELEMENTS HAVE AN IMPACT ON PHYSICAL BARRIERS (SUCH AS GUT MUCOSAL BARRIER AND SKIN), ON THE IMMUNE SYSTEM RESPONSE AND ON MICROBIOME MODULATION. PROTEIN DEFICIENCIES CAN COMPROMISE INNATE AND ADAPTIVE IMMUNE FUNCTIONS; ARGININE AVAILABILITY CAN AFFECT THE IMMUNE RESPONSE IN INJURED STATES AND OTHER DISEASE PROCESSES; EPA AND DHA CAN MODULATE BOTH INNATE AND ADAPTIVE IMMUNITY; PREBIOTICS HAVE A BENEFICIAL EFFECT ON THE FUNCTIONING OF THE IMMUNE SYSTEM. ZINC, COPPER, SELENIUM AND IRON ARE INVOLVED IN THE CORRECT DEVELOPMENT AND FUNCTION OF THE IMMUNE SYSTEM. VITAMINS D, E, A, B AND C HAVE A ROLE ON IMMUNE SYSTEM THROUGH DIFFERENT MECHANISMS OF ACTION. SINCE A COMPLEX INTERPLAY EXISTS BETWEEN DIET, MICROBIOME AND EPIGENETIC FACTORS WHICH DETERMINE NUTRIENT-INDUCED CHANGES ON THE IMMUNE FUNCTION, THE EFFECT OF EACH SINGLE NUTRIENT MAY BE DIFFICULT TO STUDY. WELL-DESIGNED INTERVENTION STUDIES, INVESTIGATING THE EFFECTS OF WHOLE DIETARY PATTERN, SHOULD BE PERFORMED TO CLARIFY IMPACT OF FOODS ON THE IMMUNE FUNCTION AND DISEASE RISK. 2021 11 5076 32 PHYSIOLOGICAL AND ENVIRONMENTAL FACTORS AFFECTING CANCER RISK AND PROGNOSIS IN OBESITY. OBESITY RESULTS FROM A CHRONIC EXCESSIVE ACCUMULATION OF ADIPOSE TISSUE DUE TO A LONG-TERM IMBALANCE BETWEEN ENERGY INTAKE AND EXPENDITURE. AVAILABLE EPIDEMIOLOGICAL AND CLINICAL DATA STRONGLY SUPPORT THE LINKS BETWEEN OBESITY AND CERTAIN CANCERS. EMERGING CLINICAL AND EXPERIMENTAL FINDINGS HAVE IMPROVED OUR UNDERSTANDING OF THE ROLES OF KEY PLAYERS IN OBESITY-ASSOCIATED CARCINOGENESIS SUCH AS AGE, SEX (MENOPAUSE), GENETIC AND EPIGENETIC FACTORS, GUT MICROBIOTA AND METABOLIC FACTORS, BODY SHAPE TRAJECTORY OVER LIFE, DIETARY HABITS, AND GENERAL LIFESTYLE. IT IS NOW WIDELY ACCEPTED THAT THE CANCER-OBESITY RELATIONSHIP DEPENDS ON THE SITE OF CANCER, THE SYSTEMIC INFLAMMATORY STATUS, AND MICRO ENVIRONMENTAL PARAMETERS SUCH AS LEVELS OF INFLAMMATION AND OXIDATIVE STRESS IN TRANSFORMING TISSUES. WE HEREBY REVIEW RECENT ADVANCES IN OUR UNDERSTANDING OF CANCER RISK AND PROGNOSIS IN OBESITY WITH RESPECT TO THESE PLAYERS. WE HIGHLIGHT HOW THE LACK OF THEIR CONSIDERATION CONTRIBUTED TO THE CONTROVERSY OVER THE LINK BETWEEN OBESITY AND CANCER IN EARLY EPIDEMIOLOGICAL STUDIES. FINALLY, THE LESSONS AND CHALLENGES OF INTERVENTIONS FOR WEIGHT LOSS AND BETTER CANCER PROGNOSIS, AND THE MECHANISMS OF WEIGHT GAIN IN SURVIVORS ARE ALSO DISCUSSED. 2023 12 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 13 4803 28 OBESITY AND MALE INFERTILITY. THE WORLDWIDE PREVALENCE OF OBESITY IS INCREASING AMONG BOTH SEXES, WITH ASSOCIATED IMPACTS ON CHRONIC HEALTH AND MEDICAL COMORBIDITIES. SIMILARLY, THE EFFECTS OF OBESITY ON REPRODUCTIVE HEALTH ARE INCREASINGLY BEING RECOGNIZED. ADIPOSITY IS ASSOCIATED WITH REDUCED FERTILITY IN MEN, WITH A COMPLEX AND MULTIFACTORIAL ETIOLOGY. THE REPORTED EFFECTS OF OBESITY ON SEMEN PARAMETERS AND IMPAIRED FERTILITY ARE CONTRASTING, WITH SOME STUDIES SHOWING A CLEAR REDUCTION IN REPRODUCTIVE OUTCOMES ASSOCIATED WITH INCREASED BODY MASS INDEX, WHILE OTHERS DO NOT SHOW SUCH IMPACTS. THESE CONTROVERSIES MAY BE DUE TO THE COMPLEX PATHOPHYSIOLOGY AND INTERPLAY BETWEEN GONADOTROPINS AND END ORGANS, AS WELL AS GENETIC AND EPIGENETIC CHANGES AND OXIDATIVE STRESS ON MALE FERTILITY AND FUNCTION. THESE DIFFERENT ASPECTS HAVE LED TO HETEROGENEOUS PARTICIPANTS IN STUDIES AND VARYING IMPLICATIONS FOR ASSISTED REPRODUCTIVE OUTCOMES AS WELL AS OFFSPRING HEALTH. TREATMENT MODALITIES TO MANAGE OBESITY INCLUDE LIFESTYLE, MEDICAL, AND SURGICAL OPTIONS, WITH EMERGING AND EFFECTIVE MEDICAL TREATMENTS SHOWING PROMISE IN REPRODUCTIVE OUTCOMES. 2023 14 3576 49 IMPACT OF NUTRITION ON POLLUTANT TOXICITY: AN UPDATE WITH NEW INSIGHTS INTO EPIGENETIC REGULATION. EXPOSURE TO ENVIRONMENTAL POLLUTANTS IS A GLOBAL HEALTH PROBLEM AND IS ASSOCIATED WITH THE DEVELOPMENT OF MANY CHRONIC DISEASES, INCLUDING CARDIOVASCULAR DISEASE, DIABETES AND METABOLIC SYNDROME. THERE IS A GROWING BODY OF EVIDENCE THAT NUTRITION CAN BOTH POSITIVELY AND NEGATIVELY MODULATE THE TOXIC EFFECTS OF POLLUTANT EXPOSURE. DIETS HIGH IN PROINFLAMMATORY FATS, SUCH AS LINOLEIC ACID, CAN EXACERBATE POLLUTANT TOXICITY, WHEREAS DIETS RICH IN BIOACTIVE AND ANTI-INFLAMMATORY FOOD COMPONENTS, INCLUDING OMEGA-3 FATTY ACIDS AND POLYPHENOLS, CAN ATTENUATE TOXICANT-ASSOCIATED INFLAMMATION. PREVIOUSLY, RESEARCHERS HAVE ELUCIDATED DIRECT MECHANISMS OF NUTRITIONAL MODULATION, INCLUDING ALTERATION OF NUCLEAR FACTOR KAPPA-LIGHT-CHAIN-ENHANCER OF ACTIVATED B CELLS (NF-KAPPAB) SIGNALING, BUT RECENTLY, INCREASED FOCUS HAS BEEN GIVEN TO THE WAYS IN WHICH NUTRITION AND POLLUTANTS AFFECT EPIGENETICS. NUTRITION HAS BEEN DEMONSTRATED TO MODULATE EPIGENETIC MARKERS THAT HAVE BEEN LINKED EITHER TO INCREASED DISEASE RISKS OR TO PROTECTION AGAINST DISEASES. OVERNUTRITION (I.E. OBESITY) AND UNDERNUTRITION (I.E. FAMINE) HAVE BEEN OBSERVED TO ALTER PRENATAL EPIGENETIC TAGS THAT MAY INCREASE THE RISK OF OFFSPRING DEVELOPING DISEASE LATER IN LIFE. CONVERSELY, BIOACTIVE FOOD COMPONENTS, INCLUDING CURCUMIN, HAVE BEEN SHOWN TO ALTER EPIGENETIC MARKERS THAT SUPPRESS THE ACTIVATION OF NF-KAPPAB, THUS REDUCING INFLAMMATORY RESPONSES. EXPOSURE TO POLLUTANTS ALSO ALTERS EPIGENETIC MARKERS AND MAY CONTRIBUTE TO INFLAMMATION AND DISEASE. IT HAS BEEN DEMONSTRATED THAT POLLUTANTS, VIA EPIGENETIC MODULATIONS, CAN INCREASE THE ACTIVATION OF NF-KAPPAB AND UPREGULATE MICRORNAS ASSOCIATED WITH INFLAMMATION, CARDIAC INJURY AND OXIDATIVE DAMAGE. IMPORTANTLY, RECENT EVIDENCE SUGGESTS THAT NUTRITIONAL COMPONENTS, INCLUDING EPIGALLOCATECHIN GALLATE (EGCG), CAN PROTECT AGAINST POLLUTANT-INDUCED INFLAMMATION THROUGH EPIGENETIC REGULATION OF PROINFLAMMATORY TARGET GENES OF NF-KAPPAB. FURTHER RESEARCH IS NEEDED TO BETTER UNDERSTAND HOW NUTRITION CAN MODULATE POLLUTANT TOXICITY THROUGH EPIGENETIC REGULATION. THEREFORE, THE OBJECTIVE OF THIS REVIEW IS TO ELUCIDATE THE CURRENT EVIDENCE LINKING EPIGENETIC CHANGES TO POLLUTANT-INDUCED DISEASES AND HOW THIS REGULATION MAY BE MODULATED BY NUTRIENTS ALLOWING FOR THE DEVELOPMENT OF FUTURE PERSONALIZED LIFESTYLE INTERVENTIONS. 2017 15 5072 35 PHYSICAL EXERCISE POSITIVELY INFLUENCES BREAST CANCER EVOLUTION. BREAST CANCER IS ONE OF THE MOST COMMONLY DIAGNOSED TYPES OF CANCER IN WOMEN. ITS PATHOGENESIS INVOLVES GENETIC, HORMONAL, AND ENVIRONMENTAL FACTORS. A LARGE BODY OF EVIDENCE INDICATES THAT PHYSICAL ACTIVITY HAS POSITIVE EFFECTS ON EVERY ASPECT OF BREAST CANCER EVOLUTION, INCLUDING PREVENTION, MEDICAL TREATMENT, AND AFTERCARE CLINICAL SETTINGS. THUS, DIFFERENT TYPES OF EXERCISE CAN INFLUENCE THE PREVENTION AND PROGRESSION OF THE DISEASE THROUGH SEVERAL COMMON MECHANISMS, SUCH AS REDUCTION OF INSULIN RESISTANCE AND IMPROVEMENT OF IMMUNITY AND CARDIOVASCULAR FUNCTION. FURTHERMORE, ACUTE AND CHRONIC SYMPTOMS OF BREAST CANCER, SUCH AS CACHEXIA, MUSCLE MASS LOSS, FATIGUE, CARDIOTOXICITY, WEIGHT GAIN, HORMONE ALTERATIONS, BONE LOSS, AND PSYCHOLOGIC ADVERSE EFFECTS, MAY ALL BE FAVORABLY INFLUENCED BY REGULAR EXERCISE. WE REVIEW THE RELATION OF INTENSITY AND DURATION OF EXERCISE WITH POTENTIAL PATHOPHYSIOLOGIC PATHWAYS, INCLUDING OBESITY-RELATED HORMONES AND SEX STEROID HORMONE PRODUCTION, OXIDATIVE STRESS, EPIGENETIC ALTERATIONS SUCH AS DNA HYPOMETHYLATION, AND CHANGES IN TELOMERE LENGTH, WITHIN THE CONTEXT OF THE BENEFICIAL EFFECTS OF EXERCISE. THE POTENTIAL ROLE OF EXERCISE IN REDUCING THE INTENSITY OF THE ADVERSE EFFECTS THAT RESULT FROM BREAST CANCER AND ANTICANCER TREATMENT IS ALSO DISCUSSED. 2017 16 5558 35 ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY: PROPOSED MECHANISMS AND REVIEW OF THE LITERATURE. THE AETIOLOGY OF OBESITY HAS BEEN ATTRIBUTED TO SEVERAL FACTORS (ENVIRONMENTAL, DIETARY, LIFESTYLE, HOST, AND GENETIC FACTORS); HOWEVER NONE OF THESE FULLY EXPLAIN THE INCREASE IN THE PREVALENCE OF OBESITY WORLDWIDE. GUT MICROBIOTA LOCATED AT THE INTERFACE OF HOST AND ENVIRONMENT IN THE GUT ARE A NEW AREA OF RESEARCH BEING EXPLORED TO EXPLAIN THE EXCESS ACCUMULATION OF ENERGY IN OBESE INDIVIDUALS AND MAY BE A POTENTIAL TARGET FOR THERAPEUTIC MANIPULATION TO REDUCE HOST ENERGY STORAGE. SEVERAL MECHANISMS HAVE BEEN SUGGESTED TO EXPLAIN THE ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY SUCH AS SHORT CHAIN FATTY ACID PRODUCTION, STIMULATION OF HORMONES, CHRONIC LOW-GRADE INFLAMMATION, LIPOPROTEIN AND BILE ACID METABOLISM, AND INCREASED ENDOCANNABINOID RECEPTOR SYSTEM TONE. HOWEVER, EVIDENCE FROM ANIMAL AND HUMAN STUDIES CLEARLY INDICATES CONTROVERSIES IN DETERMINING THE CAUSE OR EFFECT RELATIONSHIP BETWEEN THE GUT MICROBIOTA AND OBESITY. METAGENOMICS BASED STUDIES INDICATE THAT FUNCTIONALITY RATHER THAN THE COMPOSITION OF GUT MICROBIOTA MAY BE IMPORTANT. FURTHER MECHANISTIC STUDIES CONTROLLING FOR ENVIRONMENTAL AND EPIGENETIC FACTORS ARE THEREFORE REQUIRED TO HELP UNRAVEL OBESITY PATHOGENESIS. 2016 17 6169 35 THE GUT MICROBIOTA AND HEALTHY AGING: A MINI-REVIEW. THE GUT MICROBIOTA SHOWS A WIDE INTER-INDIVIDUAL VARIATION, BUT ITS WITHIN-INDIVIDUAL VARIATION IS RELATIVELY STABLE OVER TIME. A FUNCTIONAL CORE MICROBIOME, PROVIDED BY ABUNDANT BACTERIAL TAXA, SEEMS TO BE COMMON TO VARIOUS HUMAN HOSTS REGARDLESS OF THEIR GENDER, GEOGRAPHIC LOCATION, AND AGE. WITH ADVANCING CHRONOLOGICAL AGE, THE GUT MICROBIOTA BECOMES MORE DIVERSE AND VARIABLE. HOWEVER, WHEN MEASURES OF BIOLOGICAL AGE ARE USED WITH ADJUSTMENT FOR CHRONOLOGICAL AGE, OVERALL RICHNESS DECREASES, WHILE A CERTAIN GROUP OF BACTERIA ASSOCIATED WITH FRAILTY INCREASES. THIS HIGHLIGHTS THE IMPORTANCE OF CONSIDERING BIOLOGICAL OR FUNCTIONAL MEASURES OF AGING. STUDIES USING MODEL ORGANISMS INDICATE THAT AGE-RELATED GUT DYSBIOSIS MAY CONTRIBUTE TO UNHEALTHY AGING AND REDUCED LONGEVITY. THE GUT MICROBIOME DEPENDS ON THE HOST NUTRIENT SIGNALING PATHWAYS FOR ITS BENEFICIAL EFFECTS ON HOST HEALTH AND LIFESPAN, AND GUT DYSBIOSIS DISRUPTING THE INTERDEPENDENCE MAY DIMINISH THE BENEFICIAL EFFECTS OR EVEN HAVE REVERSE EFFECTS. GUT DYSBIOSIS CAN TRIGGER THE INNATE IMMUNE RESPONSE AND CHRONIC LOW-GRADE INFLAMMATION, LEADING TO MANY AGE-RELATED DEGENERATIVE PATHOLOGIES AND UNHEALTHY AGING. THE GUT MICROBIOTA COMMUNICATES WITH THE HOST THROUGH VARIOUS BIOMOLECULES, NUTRIENT SIGNALING-INDEPENDENT PATHWAYS, AND EPIGENETIC MECHANISMS. DISTURBANCE OF THESE COMMUNICATIONS BY AGE-RELATED GUT DYSBIOSIS CAN AFFECT THE HOST HEALTH AND LIFESPAN. THIS MAY EXPLAIN THE IMPACT OF THE GUT MICROBIOME ON HEALTH AND AGING. 2018 18 6379 33 THE ROLE OF NUTRITION ON META-INFLAMMATION: INSIGHTS AND POTENTIAL TARGETS IN COMMUNICABLE AND CHRONIC DISEASE MANAGEMENT. PURPOSE OF REVIEW: CHRONIC LOW-GRADE INFLAMMATION MAY CONTRIBUTE TO THE ONSET AND PROGRESSION OF COMMUNICABLE AND CHRONIC DISEASES. THIS REVIEW EXAMINED THE EFFECTS AND EVENTUAL MEDIATION ROLES OF DIFFERENT NUTRITIONAL FACTORS ON INFLAMMATION. RECENT FINDINGS: POTENTIAL NUTRITIONAL COMPOUNDS INFLUENCING INFLAMMATION PROCESSES INCLUDE MACRO AND MICRONUTRIENTS, BIOACTIVE MOLECULES (POLYPHENOLS), SPECIFIC FOOD COMPONENTS, AND CULINARY INGREDIENTS AS WELL AS STANDARDIZED DIETARY PATTERNS, EATING HABITS, AND CHRONONUTRITION FEATURES. THEREFORE, RESEARCH IN THIS FIELD IS STILL REQUIRED, TAKING INTO ACCOUNT CRITICAL ASPECTS OF HETEROGENEITY INCLUDING TYPE OF POPULATION, MINIMUM AND MAXIMUM INTAKES AND ADVERSE EFFECTS, COOKING METHODS, PHYSIOPATHOLOGICAL STATUS, AND TIMES OF INTERVENTION. MOREOVER, THE INTEGRATIVE ANALYSIS OF TRADITIONAL VARIABLES (AGE, SEX, METABOLIC PROFILE, CLINICAL HISTORY, BODY PHENOTYPE, HABITUAL DIETARY INTAKE, PHYSICAL ACTIVITY LEVELS, AND LIFESTYLE) TOGETHER WITH INDIVIDUALIZED ISSUES (GENETIC BACKGROUND, EPIGENETIC SIGNATURES, MICROBIOTA COMPOSITION, GENE EXPRESSION PROFILES, AND METABOLOMIC FINGERPRINTS) MAY CONTRIBUTE TO THE KNOWLEDGE AND PRESCRIPTION OF MORE PERSONALIZED TREATMENTS AIMED TO IMPROVING THE PRECISION MEDICAL MANAGEMENT OF INFLAMMATION AS WELL AS THE DESIGN OF ANTI-INFLAMMATORY DIETS IN CHRONIC AND COMMUNICABLE DISEASES. 2022 19 2869 39 FUNCTIONAL FOODS AND HEALTH EFFECTS: A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE. BACKGROUND: INCREASED CONSUMER S INTEREST IN HEALTH HAS DRIVEN THE DEVELOPMENT OF FOODS THAT OFFER SPECIFIC BENEFICIAL EFFECTS. THE LIST OF FOODS AND INGREDIENTS INCLUDES ESSENTIAL AND NON-ESSENTIAL NUTRIENTS, PLANT AND MARINE COMPONENTS, WHOLE FOODS, MICROORGANISMS, MICROALGAE AND TECHNOLOGICAL APPROACHES. TRADITIONALLY, HEALTH OUTCOMES FOCUSSED ON THE PREVENTION OF CHRONIC DISEASES BUT HEALTH TARGETS HAVE EXPANDED TO COVER AREAS SUCH AS BRAIN HEALTH, INFLAMMATION, EYE HEALTH, WOMEN S HEALTH, HEALTHY AGEING AND BEAUTY. OBJECTIVE: THIS REVIEW HIGHLIGHTS, FROM A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE, DIFFERENTIAL ASPECTS ON DESIGNING AND INTERPRETING HUMAN STUDIES TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. RESULTS: DESPITE THE AVAILABLE EVIDENCE FROM IN VITRO, ANIMAL AND OBSERVATIONAL STUDIES, WELLDESIGNED HUMAN STUDIES ARE NECESSARY TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. INTERVENTION TRIALS WITH FOODS ARE COMPLEX AS THEY IMPLY LIMITATIONS DUE TO METHODOLOGICAL, FOOD-RELATED AND HOST-RELATED FACTORS. THE USE OF RESPONSIVE, VALIDATED AND CLINICALLY RELEVANT MARKERS BECOMES ESSENTIAL EVEN THOUGH THERE IS A LACK OF RELIABLE BIOMARKERS OF EXPOSURE FOR MANY BIOACTIVES. FURTHERMORE, THE EFFECT OF MODULATING FACTORS SUCH AS SUBCLINICAL INFLAMMATION, GUT MICROBIOTA AND GENETIC VARIABILITY SHOULD BE TAKEN INTO ACCOUNT. MULTIPLE INDICATORS MAY PROVIDE A MORE RELIABLE ALTERNATIVE TO ASSESS PHYSIOLOGICAL PROCESSES WHILE EMERGING BIOMARKERS (MICRORNAS, EPIGENETIC CHANGES) CONSTITUTE A PROMISING APPROACH. ADDITIONALLY, THE MAGNITUDE OF THE CHANGE IS CRITICAL TO SUPPORT ANY HEALTH EFFECT ALTHOUGH INTERVENTIONS MAY HAVE A LIMITED CLINICAL IMPACT BUT BE EPIDEMIOLOGICALLY RELEVANT. ALSO, BASED ON THE AVAILABLE DATA, THE PREMISE THAT BIOACTIVESCONTAINING FOODS ARE SAFE MAY BE QUESTIONABLE. CONCLUSION: AN INTEGRATED APPROACH INCLUDING MULTIPLE BIOMARKERS, GENETIC VARIABILITY, EFFECT OF GUT MICROBIOTA AND RISK/BENEFIT ASSESSMENT SHOULD BE USED TO SUPPORT THE POTENTIAL HEALTH EFFECTS OF FUNCTIONAL FOODS. 2016 20 6034 46 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