1 6169 120 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 2 5558 29 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 3 2855 42 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 4 3546 36 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 5 6346 30 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 6 625 30 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 7 6109 31 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 6252 27 THE MICROBIOME AND CANCER: IMPLICATIONS FOR ONCOLOGY NURSING SCIENCE. BACKGROUND: APPROXIMATELY 1.6 MILLION AMERICANS WERE DIAGNOSED WITH CANCER IN 2014. TO COMBAT THEIR DISEASE, MANY INDIVIDUALS RECEIVED EITHER CURATIVE OR PALLIATIVE TREATMENTS THAT PRODUCED UNDESIRED SYMPTOMS. THESE SYMPTOMS, WHICH OFTEN CAUSE SIGNIFICANT DISTRESS FOR INDIVIDUALS COPING WITH CANCER, MAY SHARE BIOLOGIC UNDERPINNINGS SUCH AS EPIGENETIC CHANGES AND IMMUNE DYSREGULATION. ALTERATIONS IN THE NORMAL FLORA OF THE GUT MAY ALSO INFLUENCE CANCER SYMPTOMS. OBJECTIVE: THE AIM OF THIS REVIEW IS TO DESCRIBE THE EMERGING ROLE FOR THE GUT MICROBIOME IN CANCER RESEARCH, ESPECIALLY THE POTENTIAL RELATIONSHIP BETWEEN THE GUT MICROBIOME AND CANCER SYMPTOMS. METHODS: EXTANT LITERATURE WAS REVIEWED AND SYNTHESIZED. RESULTS: THE MAJORITY OF STUDIES LINKING THE GUT MICROBIOTA AND CANCER ARE ANIMAL MODELS AND FOCUS ON THE RELATIONSHIP BETWEEN DYSBIOSIS AND COLORECTAL CANCER. EMERGING EVIDENCE SUPPORTS THAT THE "GUT-BRAIN" CONNECTION IS A PLAUSIBLE MECHANISM FOR "PSYCHONEUROLOGICAL" CANCER SYMPTOMS SUCH AS DEPRESSION, PAIN, AND FATIGUE. CONCLUSIONS: THERE IS COMPELLING EVIDENCE THAT THE GUT MICROBIOTA AFFECTS CANCER VIA SEVERAL MECHANISMS, INCLUDING MICROBIAL DIVERSITY AND NUMBER, METABOLISM, AND/OR IMMUNE INITIATION. HOWEVER, MORE RESEARCH IS NECESSARY TO ELUCIDATE THESE MECHANISMS, PARTICULARLY AMONG A VARIETY OF CANCERS AND CANCER-RELATED SYMPTOMS. IMPLICATIONS FOR PRACTICE: A BETTER UNDERSTANDING OF THE ROLE OF THE GUT MICROBIOTA IN CANCER SYMPTOMS MAY LEAD TO THE DEVELOPMENT OF TARGETED INDIVIDUALIZED INTERVENTIONS AFFECTING THE GUT MICROBIOTA THAT PREVENT OR AMELIORATE DYSBIOSIS, THEREBY REDUCING SYMPTOMS. THESE INTERVENTIONS MAY EMPHASIZE SELF-CARE MANAGEMENT STRATEGIES ESSENTIAL FOR WELLNESS, SUCH AS DIET, NUTRITION, AND STRESS REDUCTION. 2016 9 3676 40 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS. 2018 10 3172 34 GUT MICROBIOTA AND RISK OF DEVELOPING CELIAC DISEASE. GUT MICROBIOTA SHAPES THE DEVELOPMENT OF THE MUCOSAL IMMUNE SYSTEM AND MAY PROVIDE PROTECTION AGAINST IMMUNE-MEDIATED DISEASES. CELIAC DISEASE (CD) IS A CHRONIC INFLAMMATORY CONDITION TRIGGERED BY DIETARY GLUTEN PROTEINS, RECENTLY ASSOCIATED WITH GUT MICROBIOTA ALTERATIONS IN CROSS-SECTIONAL STUDIES COMPARING PATIENTS AND CONTROLS. WHETHER OR NOT THESE DIFFERENCES ARE CAUSALLY RELATED TO THE DISEASE HAS YET TO BE ELUCIDATED, BUT EVALUATION OF SPECIFIC BACTERIA ISOLATED FROM CD PATIENTS IN EXPERIMENTAL MODELS SUGGESTS THAT THEY CAN PROMOTE AN ADVERSE RESPONSE TO DIETARY GLUTEN, WHEREAS OTHER COMMENSAL BACTERIA CAN BE PROTECTIVE. GENETIC AND ENVIRONMENTAL FACTORS ASSOCIATED WITH INCREASED CD RISK HAVE ALSO BEEN LINKED TO SHIFTS IN THE GUT MICROBIOTA COMPOSITION IN INFANTS EARLY IN LIFE. EPIGENETIC MECHANISMS ALSO SEEM TO PLAY AN IMPORTANT ROLE IN MODULATING GUT MICROBIOTA COMPOSITION AND FUNCTION AND, THEORETICALLY, COULD ALSO INFLUENCE CD RISK. HERE, WE REVIEW THE CURRENT KNOWLEDGE ON HOW HOST GENETICS, ENVIRONMENTAL FACTORS, AND EPIGENETIC MODIFICATIONS COULD MODULATE GUT MICROBIOTA FUNCTIONALITY AND HOW THIS MAY INFLUENCE CD RISK. GREATER UNDERSTANDING OF THE ROLE OF THIS TRIAD IN CD ONSET AND PATHOGENESIS WILL BE VALUABLE IN DESIGNING PROOF-OF CONCEPT INTERVENTIONS IN THE GUT ECOSYSTEM, WITH A VIEW TO IMPROVING CD MANAGEMENT. 2016 11 1395 37 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 12 2617 43 EPIGENOME TARGETING BY PROBIOTIC METABOLITES. BACKGROUND: THE INTESTINAL MICROBIOTA PLAYS AN IMPORTANT ROLE IN IMMUNE DEVELOPMENT AND HOMEOSTASIS. A DISTURBED MICROBIOTA DURING EARLY INFANCY IS ASSOCIATED WITH AN INCREASED RISK OF DEVELOPING INFLAMMATORY AND ALLERGIC DISEASES LATER IN LIFE. THE MECHANISMS UNDERLYING THESE EFFECTS ARE POORLY UNDERSTOOD BUT ARE LIKELY TO INVOLVE ALTERATIONS IN MICROBIAL PRODUCTION OF FERMENTATION-DERIVED METABOLITES, WHICH HAVE POTENT IMMUNE MODULATING PROPERTIES AND ARE REQUIRED FOR MAINTENANCE OF HEALTHY MUCOSAL IMMUNE RESPONSES. PROBIOTICS ARE BENEFICIAL BACTERIA THAT HAVE THE CAPACITY TO ALTER THE COMPOSITION OF BACTERIAL SPECIES IN THE INTESTINE THAT CAN IN TURN INFLUENCE THE PRODUCTION OF FERMENTATION-DERIVED METABOLITES. PRINCIPAL AMONG THESE METABOLITES ARE THE SHORT-CHAIN FATTY ACIDS BUTYRATE AND ACETATE THAT HAVE POTENT ANTI-INFLAMMATORY ACTIVITIES IMPORTANT IN REGULATING IMMUNE FUNCTION AT THE INTESTINAL MUCOSAL SURFACE. THEREFORE STRATEGIES AIMED AT RESTORING THE MICROBIOTA PROFILE MAY BE EFFECTIVE IN THE PREVENTION OR TREATMENT OF ALLERGIC AND INFLAMMATORY DISEASES. PRESENTATION OF THE HYPOTHESIS: PROBIOTIC BACTERIA HAVE DIVERSE EFFECTS INCLUDING ALTERING MICROBIOTA COMPOSITION, REGULATING EPITHELIAL CELL BARRIER FUNCTION AND MODULATING OF IMMUNE RESPONSES. THE PRECISE MOLECULAR MECHANISMS MEDIATING THESE PROBIOTIC EFFECTS ARE NOT WELL UNDERSTOOD. SHORT-CHAIN FATTY ACIDS SUCH AS BUTYRATE ARE A CLASS OF HISTONE DEACETYLASE INHIBITORS IMPORTANT IN THE EPIGENETIC CONTROL OF HOST CELL RESPONSES. IT IS HYPOTHESIZED THAT THE BIOLOGICAL FUNCTION OF PROBIOTICS MAY BE A RESULT OF EPIGENETIC MODIFICATIONS THAT MAY EXPLAIN THE WIDE RANGE OF EFFECTS OBSERVED. STUDIES DELINEATING THE EFFECTS OF PROBIOTICS ON SHORT-CHAIN FATTY ACID PRODUCTION AND THE EPIGENETIC ACTIONS OF SHORT-CHAIN FATTY ACIDS WILL ASSIST IN UNDERSTANDING THE ASSOCIATION BETWEEN MICROBIOTA AND ALLERGIC OR AUTOIMMUNE DISORDERS. TESTING THE HYPOTHESIS: WE PROPOSE THAT TREATMENT WITH SPECIFIC PROBIOTIC BACTERIA UNDER IN VIVO CONDITIONS WOULD OFFER THE IDEAL CONDITIONS TO EXAMINE THE MICROBIOLOGICAL, IMMUNOLOGICAL AND EPIGENETIC MECHANISMS OF ACTION. ADVANCES IN EPIGENETIC TECHNOLOGY NOW ALLOW INVESTIGATORS TO BETTER UNDERSTAND THE COMPLEX BIOLOGICAL PROPERTIES OF PROBIOTICS AND THEIR METABOLITES. IMPLICATIONS OF THE HYPOTHESIS: DETERMINING THE PRECISE MECHANISMS OF PROBIOTIC ACTION WILL LEAD TO MORE SPECIFIC AND EFFICACIOUS THERAPEUTIC STRATEGIES IN THE PREVENTION OR TREATMENT OF CHRONIC INFLAMMATORY CONDITIONS. 2010 13 2916 35 GENE VARIANTS AS DETERMINANTS OF LONGEVITY: FOCUS ON THE INFLAMMATORY FACTORS. HUMAN LONGEVITY IS AN EXTREMELY COMPLEX TRAIT WITH VARIOUS GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS ACTING UPON THE LONGEVITY PHENOTYPE. IT IS NOW BECOMING EVIDENT THAT WHILST THE GENETIC DIFFERENCES CONTRIBUTE ONLY MODESTLY TO LIFE EXPECTANCY BEFORE THE AGE OF 60 YEARS, THEIR IMPACT ON SURVIVAL BECOMES MORE PROMINENT AT THE EXTREME AGES. SEVERAL LONGEVITY GENE CANDIDATES HAVE EMERGED DURING THE PAST DECADE; THE MAJORITY OF THEM ARE RELATED EITHER TO INFLAMMATORY FUNCTIONS, STRESS RESPONSE OR TO LIPID AND GLUCOSE METABOLISM. THE VARIANTS OF INFLAMMATORY AND IMMUNE RESPONSE GENES ARE OF SPECIAL INTEREST SINCE ADVANCING AGES IS ACCOMPANIED BY A DECLINE IN SEVERAL IMMUNE FUNCTIONS--A PHENOMENON CALLED IMMUNOSENESCENCE. PARADOXICALLY, AGEING IS ALSO CHARACTERISED BY CHRONIC LOW-GRADE INFLAMMATION TERMED "INFLAMMAGING", WHICH MANIFESTS AS A TWO- TO FOURFOLD INCREASE IN THE PRODUCTION OF PROINFLAMMATORY CYTOKINES AND ACUTE PHASE PROTEINS. THESE CONTRASTING PHENOMENA PROVIDE A FUNCTIONAL RATIONALE OF HOW THE GENETIC DIFFERENCES IN INFLAMMATORY MEDIATORS MAY MODIFY THE LIFE SPAN OF THE ELDERLY. BESIDES DESCRIBING THE PRE-EXISTING INFLAMMATORY AND IMMUNE-RELATED LONGEVITY GENE VARIANTS, IN THIS REVIEW, WE ALSO EXPLAIN SOME OF THE THEORETICAL AND PRACTICAL CHALLENGES THAT GENETIC LONGEVITY STUDIES OFTEN ENCOUNTER. 2010 14 4273 36 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 15 5263 32 PROMISING BIOMARKERS OF HUMAN AGING: IN SEARCH OF A MULTI-OMICS PANEL TO UNDERSTAND THE AGING PROCESS FROM A MULTIDIMENSIONAL PERSPECTIVE. THE AGING PROCESS HAS BEEN LINKED TO THE OCCURRENCE OF CHRONIC DISEASES AND FUNCTIONAL IMPAIRMENTS, INCLUDING CANCER, SARCOPENIA, FRAILTY, METABOLIC, CARDIOVASCULAR, AND NEURODEGENERATIVE DISEASES. NONETHELESS, AGING IS HIGHLY VARIABLE AND HETEROGENEOUS AND REPRESENTS A CHALLENGE FOR ITS CHARACTERIZATION. IN THIS SENSE, INTRINSIC CAPACITY (IC) STANDS AS A NOVEL PERSPECTIVE BY THE WORLD HEALTH ORGANIZATION, WHICH INTEGRATES THE INDIVIDUAL WELLBEING, ENVIRONMENT, AND RISK FACTORS TO UNDERSTAND AGING. HOWEVER, THERE IS A LACK OF QUANTITATIVE AND QUALITATIVE ATTRIBUTES TO DEFINE IT OBJECTIVELY. THEREFORE, IN THIS REVIEW WE ATTEMPT TO SUMMARIZE THE MOST RELEVANT AND PROMISING BIOMARKERS DESCRIBED IN CLINICAL STUDIES AT DATE OVER DIFFERENT MOLECULAR LEVELS, INCLUDING EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS, AND THE MICROBIOME. TO AID GERONTOLOGISTS, GERIATRICIANS, AND BIOMEDICAL RESEARCHERS TO UNDERSTAND THE AGING PROCESS THROUGH THE IC. AGING BIOMARKERS REFLECT THE PHYSIOLOGICAL STATE OF INDIVIDUALS AND THE UNDERLYING MECHANISMS RELATED TO HOMEOSTATIC CHANGES THROUGHOUT AN INDIVIDUAL LIFESPAN; THEY DEMONSTRATED THAT AGING COULD BE MEASURED INDEPENDENTLY OF TIME (THAT MAY EXPLAIN ITS HETEROGENEITY) AND TO BE HELPFUL TO PREDICT AGE-RELATED SYNDROMES AND MORTALITY. IN SUMMARY, WE HIGHLIGHT THE AREAS OF OPPORTUNITY AND GAPS OF KNOWLEDGE THAT MUST BE ADDRESSED TO FULLY INTEGRATE BIOMEDICAL FINDINGS INTO CLINICALLY USEFUL TOOLS AND INTERVENTIONS. 2020 16 3585 28 IMPACT OF THE EXPOSOME ON THE EPIGENOME IN INFLAMMATORY BOWEL DISEASE PATIENTS AND ANIMAL MODELS. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT THAT ENCOMPASS TWO MAIN PHENOTYPES, NAMELY CROHN'S DISEASE AND ULCERATIVE COLITIS. THESE CONDITIONS OCCUR IN GENETICALLY PREDISPOSED INDIVIDUALS IN RESPONSE TO ENVIRONMENTAL FACTORS. EPIGENETICS, ACTING BY DNA METHYLATION, POST-TRANSLATIONAL HISTONES MODIFICATIONS OR BY NON-CODING RNAS, COULD EXPLAIN HOW THE EXPOSOME (OR ALL ENVIRONMENTAL INFLUENCES OVER THE LIFE COURSE, FROM CONCEPTION TO DEATH) COULD INFLUENCE THE GENE EXPRESSION TO CONTRIBUTE TO INTESTINAL INFLAMMATION. WE PERFORMED A SCOPING SEARCH USING MEDLINE TO IDENTIFY ALL THE ELEMENTS OF THE EXPOSOME THAT MAY PLAY A ROLE IN INTESTINAL INFLAMMATION THROUGH EPIGENETIC MODIFICATIONS, AS WELL AS THE UNDERLYING MECHANISMS. THE ENVIRONMENTAL FACTORS EPIGENETICALLY INFLUENCING THE OCCURRENCE OF INTESTINAL INFLAMMATION ARE THE MATERNAL LIFESTYLE (MAINLY DIET, THE OCCURRENCE OF INFECTION DURING PREGNANCY AND SMOKING); BREASTFEEDING; MICROBIOTA; DIET (INCLUDING A LOW-FIBER DIET, HIGH-FAT DIET AND DEFICIENCY IN MICRONUTRIENTS); SMOKING HABITS, VITAMIN D AND DRUGS (E.G., IBD TREATMENTS, ANTIBIOTICS AND PROBIOTICS). INFLUENCED BY BOTH MICROBIOTA AND DIET, SHORT-CHAIN FATTY ACIDS ARE GUT MICROBIOTA-DERIVED METABOLITES RESULTING FROM THE ANAEROBIC FERMENTATION OF NON-DIGESTIBLE DIETARY FIBERS, PLAYING AN EPIGENETICALLY MEDIATED ROLE IN THE INTEGRITY OF THE EPITHELIAL BARRIER AND IN THE DEFENSE AGAINST INVADING MICROORGANISMS. ALTHOUGH THE IMPACT OF SOME ENVIRONMENTAL FACTORS HAS BEEN IDENTIFIED, THE EXPOSOME-INDUCED EPIMUTATIONS IN IBD REMAIN A LARGELY UNDEREXPLORED FIELD. HOW THESE ENVIRONMENTAL EXPOSURES INDUCE EPIGENETIC MODIFICATIONS (IN TERMS OF DURATION, FREQUENCY AND THE TIMING AT WHICH THEY OCCUR) AND HOW OTHER ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD MODULATE EPIGENETICS DESERVE TO BE FURTHER INVESTIGATED. 2022 17 5076 28 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 18 6034 39 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 19 3577 34 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 20 6187 27 THE IMPACT OF IMMUNOSENESCENCE ON PULMONARY DISEASE. THE GLOBAL POPULATION IS AGING WITH SIGNIFICANT GAINS IN LIFE EXPECTANCY PARTICULARLY IN THE DEVELOPED WORLD. CONSEQUENTLY, GREATER FOCUS ON UNDERSTANDING THE PROCESSES THAT UNDERLIE PHYSIOLOGICAL AGING HAS OCCURRED. KEY FACETS OF ADVANCING AGE INCLUDE GENOMIC INSTABILITY, TELOMERE SHORTENING, EPIGENETIC CHANGES, AND DECLINES IN IMMUNE FUNCTION TERMED IMMUNOSENESCENCE. IMMUNOSENESCENCE AND ITS ASSOCIATED CHRONIC LOW GRADE SYSTEMIC "INFLAMM-AGING" CONTRIBUTE TO THE DEVELOPMENT AND PROGRESSION OF PULMONARY DISEASE IN OLDER INDIVIDUALS. THESE PHYSIOLOGICAL PROCESSES PREDISPOSE TO PULMONARY INFECTION AND CONFER SPECIFIC AND UNIQUE CLINICAL PHENOTYPES OBSERVED IN CHRONIC RESPIRATORY DISEASE INCLUDING LATE-ONSET ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND PULMONARY FIBROSIS. EMERGING CONCEPTS OF THE GUT AND AIRWAY MICROBIOME FURTHER COMPLICATE THE INTERRELATIONSHIP BETWEEN HOST AND MICROORGANISM PARTICULARLY FROM AN IMMUNOLOGICAL PERSPECTIVE AND ESPECIALLY SO IN THE SETTING OF IMMUNOSENESCENCE. THIS REVIEW FOCUSES ON OUR CURRENT UNDERSTANDING OF THE AGING PROCESS, IMMUNOSENESCENCE, AND HOW IT CAN POTENTIALLY IMPACT ON VARIOUS PULMONARY DISEASES AND THE HUMAN MICROBIOME. 2015