1 28 167 A BIOMIMETIC NATURAL SCIENCES APPROACH TO UNDERSTANDING THE MECHANISMS OF AGEING IN BURDEN OF LIFESTYLE DISEASES. THE WORLDWIDE LANDSCAPE OF AN AGEING POPULATION AND AGE-RELATED DISEASE BRINGS WITH IT HUGE SOCIO-ECONOMIC AND PUBLIC HEALTHCARE CONCERNS ACROSS NATIONS. CORRESPONDINGLY, MONUMENTAL HUMAN AND FINANCIAL RESOURCES HAVE BEEN INVESTED IN BIOMEDICAL RESEARCH, WITH A MISSION TO DECODE THE MECHANISMS OF AGEING AND HOW THESE CONTRIBUTE TO AGE-RELATED DISEASE. MULTIPLE HALLMARKS OF AGEING HAVE BEEN IDENTIFIED THAT ARE COMMON ACROSS TAXA, HIGHLIGHTING THEIR FUNDAMENTAL IMPORTANCE. THESE INCLUDE DYSREGULATED MITOCHONDRIAL METABOLISM AND TELOMERES BIOLOGY, EPIGENETIC MODIFICATIONS, CELL-MATRIX INTERACTIONS, PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, STEM CELL EXHAUSTION, INFLAMMAGEING AND IMMUNO-SENESCENCE. WHILE OUR UNDERSTANDING OF THE MOLECULAR BASIS OF AGEING IS IMPROVING, IT REMAINS A COMPLEX AND MULTIFACTORIAL PROCESS THAT REMAINS TO BE FULLY UNDERSTOOD. A KEY ASPECT OF THE SHORTFALL IN OUR UNDERSTANDING OF THE AGEING PROCESS LIES IN TRANSLATING DATA FROM STANDARD ANIMAL MODELS TO HUMANS. CONSEQUENTLY, WE SUGGEST THAT A 'BIOMIMETIC' AND COMPARATIVE APPROACH, INTEGRATING KNOWLEDGE FROM SPECIES IN THE WILD, AS OPPOSED TO INBRED GENETICALLY HOMOGENOUS LABORATORY ANIMALS, CAN PROVIDE POWERFUL INSIGHTS INTO HUMAN AGEING PROCESSES. HERE WE DISCUSS SOME PARTICULARITIES AND COMPARATIVE PATTERNS AMONG SEVERAL SPECIES FROM THE ANIMAL KINGDOM, ENDOWED WITH LONGEVITY OR SHORT LIFESPANS AND UNIQUE METABOLIC PROFILES THAT COULD BE POTENTIALLY EXPLOITED TO THE UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES. BASED UPON LESSONS FROM NATURE, WE ALSO HIGHLIGHT SEVERAL AVENUES FOR RENEWED FOCUS IN THE PATHOPHYSIOLOGY OF AGEING AND AGE-RELATED DISEASE (I.E. DIET-MICROBIOME-HEALTH AXIS, OXIDATIVE PROTEIN DAMAGE, ADAPTIVE HOMOEOSTASIS AND PLANETARY HEALTH). WE PROPOSE THAT A BIOMIMETIC ALLIANCE WITH COLLABORATIVE RESEARCH FROM DIFFERENT DISCIPLINES CAN IMPROVE OUR UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES WITH LONG-TERM SUSTAINABLE UTILITY. 2021 2 49 39 A CURRENT GENETIC AND EPIGENETIC VIEW ON HUMAN AGING MECHANISMS. THE PROCESS OF AGING IS ONE OF THE MOST COMPLEX AND INTRIGUING BIOLOGICAL PHENOMENONS. AGING IS A GENETICALLY REGULATED PROCESS IN WHICH THE ORGANISM'S MAXIMUM LIFESPAN POTENTIAL IS PRE-DETERMINED, WHILE THE RATE OF AGING IS INFLUENCED BY ENVIRONMENTAL FACTORS AND LIFESTYLE. CONSIDERING THE COMPLEXITY OF MECHANISMS INVOLVED IN THE REGULATION OF AGING PROCESS, UP TO THIS DATE THERE ISN'T A MAJOR, UNIFYING THEORY WHICH COULD EXPLAIN THEM. AS GENETIC/EPIGENETIC AND ENVIRONMENTAL FACTORS BOTH INEVITABLY INFLUENCE THE AGING PROCESS, HERE WE PRESENT A REVIEW ON THE GENETIC AND EPIGENETIC REGULATION OF THE MOST IMPORTANT MOLECULAR AND CELLULAR MECHANISMS INVOLVED IN THE PROCESS OF AGING. BASED ON THE STUDIES ON OXIDATIVE STRESS, METABOLISM, GENOME STABILITY, EPIGENETIC MODIFICATIONS AND CELLULAR SENESCENCE IN ANIMAL MODELS AND HUMANS, WE GIVE AN OVERVIEW OF KEY GENETIC AND MOLECULAR PATHWAYS RELATED TO AGING. AS MOST OF GENETIC MANIPULATIONS WHICH INFLUENCE THE AGING PROCESS ALSO AFFECT REPRODUCTION, WE DISCUSS AGING IN HUMANS AS A POST-REPRODUCTIVE GENETICALLY DETERMINED PROCESS. AFTER THE AGE OF REPRODUCTIVE SUCCESS, AGING CONTINOUSLY PROGRESSES WHICH CLINICALLY COINCIDES WITH THE ONSET OF MOST CHRONIC DISEASES, CANCERS AND DEMENTIONS. AS EVOLUTION SHAPES THE GENOMES FOR REPRODUCTIVE SUCCESS AND NOT FOR POST-REPRODUCTIVE SURVIVAL, AGING COULD BE DEFINED AS A PROTECTIVE MECHANISM WHICH ENSURES THE PRESERVATION AND PROGRESS OF SPECIES THROUGH THE MODIFICATION, TRASMISSION AND IMPROVEMENT OF GENETIC MATERIAL. 2009 3 705 41 BUILDING RISK-ON-A-CHIP MODELS TO IMPROVE BREAST CANCER RISK ASSESSMENT AND PREVENTION. PREVENTIVE ACTIONS FOR CHRONIC DISEASES HOLD THE PROMISE OF IMPROVING LIVES AND REDUCING HEALTHCARE COSTS. FOR SEVERAL DISEASES, INCLUDING BREAST CANCER, MULTIPLE RISK AND PROTECTIVE FACTORS HAVE BEEN IDENTIFIED BY EPIDEMIOLOGISTS. THE IMPACT OF MOST OF THESE FACTORS HAS YET TO BE FULLY UNDERSTOOD AT THE ORGANISM, TISSUE, CELLULAR AND MOLECULAR LEVELS. IMPORTANTLY, COMBINATIONS OF EXTERNAL AND INTERNAL RISK AND PROTECTIVE FACTORS INVOLVE COOPERATIVITY THUS, SYNERGIZING OR ANTAGONIZING DISEASE ONSET. MODELS ARE NEEDED TO MECHANISTICALLY DECIPHER CANCER RISKS UNDER DEFINED CELLULAR AND MICROENVIRONMENTAL CONDITIONS. HERE, WE BRIEFLY REVIEW BREAST CANCER RISK MODELS BASED ON 3D CELL CULTURE AND PROPOSE TO IMPROVE RISK MODELING WITH LAB-ON-A-CHIP APPROACHES. WE SUGGEST EPITHELIAL TISSUE POLARITY, DNA REPAIR AND EPIGENETIC PROFILES AS ENDPOINTS IN RISK ASSESSMENT MODELS AND DISCUSS THE DEVELOPMENT OF 'RISKS-ON-CHIPS' INTEGRATING BIOSENSORS OF THESE ENDPOINTS AND OF GENERAL TISSUE HOMEOSTASIS. RISKS-ON-CHIPS WILL HELP IDENTIFY BIOMARKERS OF RISK, SERVE AS SCREENING PLATFORMS FOR CANCER PREVENTIVE AGENTS, AND PROVIDE A BETTER UNDERSTANDING OF RISK MECHANISMS, HENCE RESULTING IN NOVEL DEVELOPMENTS IN DISEASE PREVENTION. 2013 4 627 39 BIOLOGICAL AGING PROCESSES UNDERLYING COGNITIVE DECLINE AND NEURODEGENERATIVE DISEASE. ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD) ARE AMONG THE TOP CONTRIBUTORS TO DISABILITY AND MORTALITY IN LATER LIFE. AS WITH MANY CHRONIC CONDITIONS, AGING IS THE SINGLE MOST INFLUENTIAL FACTOR IN THE DEVELOPMENT OF ADRD. EVEN AMONG OLDER ADULTS WHO REMAIN FREE OF DEMENTIA THROUGHOUT THEIR LIVES, COGNITIVE DECLINE AND NEURODEGENERATIVE CHANGES ARE APPRECIABLE WITH ADVANCING AGE, SUGGESTING SHARED PATHOPHYSIOLOGICAL MECHANISMS. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF CHANGES IN COGNITION, BRAIN MORPHOLOGY, AND NEUROPATHOLOGICAL PROTEIN ACCUMULATION ACROSS THE LIFESPAN IN HUMANS, WITH COMPLEMENTARY AND MECHANISTIC EVIDENCE FROM ANIMAL MODELS. NEXT, WE HIGHLIGHT SELECTED AGING PROCESSES THAT ARE DIFFERENTIALLY REGULATED IN NEURODEGENERATIVE DISEASE, INCLUDING ABERRANT AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, EPIGENETIC CHANGES, CEREBROVASCULAR DYSFUNCTION, INFLAMMATION, AND LIPID DYSREGULATION. WE SUMMARIZE RESEARCH ACROSS CLINICAL AND TRANSLATIONAL STUDIES TO LINK BIOLOGICAL AGING PROCESSES TO UNDERLYING ADRD PATHOGENESIS. TARGETING FUNDAMENTAL PROCESSES UNDERLYING BIOLOGICAL AGING MAY REPRESENT A YET RELATIVELY UNEXPLORED AVENUE TO ATTENUATE BOTH AGE-RELATED COGNITIVE DECLINE AND ADRD. COLLABORATION ACROSS THE FIELDS OF GEROSCIENCE AND NEUROSCIENCE, COUPLED WITH THE DEVELOPMENT OF NEW TRANSLATIONAL ANIMAL MODELS THAT MORE CLOSELY ALIGN WITH HUMAN DISEASE PROCESSES, IS NECESSARY TO ADVANCE NOVEL THERAPEUTIC DISCOVERY IN THIS REALM. 2022 5 4399 35 MODULATION OF GENOMIC AND POSTGENOMIC ALTERATIONS IN NONCANCER DISEASES AND CRITICAL PERIODS OF LIFE. GENOMIC AND POSTGENOMIC CHANGES ARE EXTENSIVELY INVESTIGATED IN CANCER RESEARCH. SIMILAR ALTERATIONS, AFFECTING GENOME, TRANSCRIPTOME, MIRNOME AND/OR PROTEOME END-POINTS, HAVE BEEN DETECTED IN A VARIETY OF OTHER CHRONIC DEGENERATIVE DISEASES, SUCH AS ATHEROSCLEROSIS, DEGENERATIVE HEART DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASES, NEUROLOGICAL DISORDERS, EYE DISEASES, DIABETES, METABOLIC SYNDROME, SKIN AGEING AND ALOPECIA. NO GENERALIZATION CAN BE MADE DUE TO THE MYRIAD OF DIVERSE CLINICAL ENTITIES CLASSIFIED AS CHRONIC DEGENERATIVE DISEASES. MOREOVER, THE DETECTION OF MOLECULAR CHANGES DOES NOT AUTOMATICALLY IMPLY THEIR CAUSAL ROLE. NEVERTHELESS, COMMON MECHANISMS, SUCH AS DNA DAMAGE, EPIGENETIC ALTERATIONS, OXIDATIVE STRESS, AND CHRONIC INFLAMMATION, IN ADDITION TO GENETIC PREDISPOSITION, ARE OFTEN INVOLVED IN NONCANCER DISEASES. WE DEBATE HERE IN MORE DETAIL THE SUBJECTS OF CARDIOVASCULAR DISEASES AND OF SKIN DISEASES. MOREOVER, WE DISCUSS OUR EXPERIMENTAL STUDIES SUGGESTING THAT GENOMIC AND POSTGENOMIC CHANGES DO ALSO OCCUR DURING CRITICAL PERIODS OF LIFE, INCLUDING THE PRENATAL LIFE, THE PERINATAL PERIOD, AND AGEING. IN ADDITION, WE COMMENT ON THE FINDING THAT STEM-DERIVED CELLS ARE MORE SUSCEPTIBLE TO MOLECULAR DAMAGE THAN MORE DIFFERENTIATED CELLS. ALL THESE DATA ARE VIEWED IN THE PERSPECTIVE OF PREVENTIVE MEDICINE. IN FACT, THERE IS EVIDENCE THAT THE GENOMIC AND POSTGENOMIC ALTERATIONS OCCURRING NOT ONLY IN SEVERAL PATHOLOGICAL CONDITIONS BUT ALSO IN PARAPHYSIOLOGICAL SITUATIONS THAT AFFECT CRITICAL PERIODS OF LIFE CAN BE MODULATED BY MEANS OF DIETARY AND PHARMACOLOGICAL AGENTS. THE DISCOVERY THAT CHEMOPREVENTIVE AGENTS ARE ALSO ABLE TO ATTENUATE NUCLEOTIDE DAMAGE IN STEM-DERIVED CELLS WARRANTS FURTHER STUDIES IN VIEW OF POSSIBLE CLINICAL APPLICATIONS. 2009 6 289 31 AGING AND INTERSTITIAL LUNG DISEASES: UNRAVELING AN OLD FORGOTTEN PLAYER IN THE PATHOGENESIS OF LUNG FIBROSIS. AGING IS A NATURAL PROCESS CHARACTERIZED BY A PROGRESSIVE FUNCTIONAL IMPAIRMENT AND REDUCED CAPACITY TO RESPOND ADAPTIVELY TO ENVIRONMENTAL STIMULI. AGING IS ASSOCIATED WITH INCREASED SUSCEPTIBILITY TO A VARIETY OF CHRONIC DISEASES, INCLUDING TYPE 2 DIABETES MELLITUS, CANCER, AND NEUROLOGICAL DISEASES. LUNG PATHOLOGIES ARE NOT THE EXCEPTION, AND THE PREVALENCE OF SEVERAL INTERSTITIAL LUNG DISEASES (ILDS), PRIMARILY IDIOPATHIC PULMONARY FIBROSIS, HAS BEEN FOUND TO INCREASE CONSIDERABLY WITH AGE. ALTHOUGH OUR UNDERSTANDING OF THE BIOLOGY OF AGING HAS ADVANCED REMARKABLY IN THE LAST 2 DECADES, THE MOLECULAR MECHANISMS LINKING AGING TO ILD REMAIN UNCLEAR. IMMUNOSENESCENCE, OXIDATIVE STRESS, ABNORMAL SHORTENING OF TELOMERES, APOPTOSIS, AND EPIGENETIC CHANGES AFFECTING GENE EXPRESSION HAVE BEEN PROPOSED TO CONTRIBUTE TO THE AGING PROCESS, AND AGING-ASSOCIATED DISEASES. HERE, WE REVIEW THE EMERGING CONCEPTS HIGHLIGHTING THE PUTATIVE AGING-ASSOCIATED ABNORMALITIES INVOLVED IN SOME HUMAN ILDS. 2010 7 6334 29 THE ROLE OF DNA METHYLATION AND HYDROXYMETHYLATION IN IMMUNOSENESCENCE. A HEALTHY FUNCTIONING IMMUNE SYSTEM IS CRITICAL TO STAVE OFF INFECTIOUS DISEASES, BUT AS HUMANS AND OTHER ORGANISMS AGE, THEIR IMMUNE SYSTEMS DECLINE. AS A RESULT, DISEASES THAT WERE READILY THWARTED IN EARLY LIFE POSE NONTRIVIAL HARM AND CAN EVEN BE DEADLY IN LATE LIFE. IMMUNOSENESCENCE IS DEFINED AS THE GENERAL DETERIORATION OF THE IMMUNE SYSTEM WITH AGE, AND IT IS CHARACTERIZED BY FUNCTIONAL CHANGES IN HEMATOPOIETIC STEM CELLS (HSCS) AND SPECIFIC BLOOD CELL TYPES AS WELL AS CHANGES IN LEVELS OF NUMEROUS FACTORS, PARTICULARLY THOSE INVOLVED IN INFLAMMATION. POTENTIAL MECHANISMS UNDERLYING IMMUNOSENESCENCE INCLUDE EPIGENETIC CHANGES SUCH AS CHANGES IN DNA METHYLATION (DNAM) AND DNA HYDROXYMETHYLATION (DNAHM) THAT OCCUR WITH AGE. THE PURPOSE OF THIS REVIEW IS TO DESCRIBE WHAT IS CURRENTLY KNOWN ABOUT THE RELATIONSHIP BETWEEN IMMUNOSENESCENCE AND THE AGE-RELATED CHANGES TO DNAM AND DNAHM, AND TO DISCUSS EXPERIMENTAL APPROACHES BEST SUITED TO FILL GAPS IN OUR UNDERSTANDING. 2019 8 2528 27 EPIGENETICS AS A KEY LINK BETWEEN PSYCHOSOCIAL STRESS AND AGING: CONCEPTS, EVIDENCE, MECHANISMS . PSYCHOSOCIAL STRESS-ESPECIALLY WHEN CHRONIC, EXCESSIVE, OR OCCURRING EARLY IN LIFE-HAS BEEN ASSOCIATED WITH ACCELERATED AGING AND INCREASED DISEASE RISK. WITH RAPID AGING OF THE WORLD POPULATION, THE NEED TO ELUCIDATE THE UNDERLYING MECHANISMS IS PRESSING, NOW MORE SO THAN EVER. AMONG MOLECULAR MECHANISMS LINKING STRESS AND AGING, THE PRESENT ARTICLE REVIEWS EVIDENCE ON THE ROLE OF EPIGENETICS, BIOCHEMICAL PROCESSES THAT CAN BE SET INTO MOTION BY STRESSORS AND IN TURN INFLUENCE GENOMIC FUNCTION AND COMPLEX PHENOTYPES, INCLUDING AGING-RELATED OUTCOMES. THE ARTICLE FURTHER PROVIDES A CONCEPTUAL MECHANISTIC FRAMEWORK ON HOW STRESS MAY DRIVE EPIGENETIC CHANGES AT SUSCEPTIBLE GENOMIC SITES, THEREBY EXERTING SYSTEMS-LEVEL EFFECTS ON THE AGING EPIGENOME WHILE ALSO REGULATING THE EXPRESSION OF MOLECULES IMPLICATED IN AGING-RELATED PROCESSES. THIS EMERGING EVIDENCE, TOGETHER WITH WORK EXAMINING RELATED BIOLOGICAL PROCESSES, BEGINS TO SHED LIGHT ON THE EPIGENETIC AND, MORE BROADLY, MOLECULAR UNDERPINNINGS OF THE LONG-HYPOTHESIZED CONNECTION BETWEEN STRESS AND AGING. . 2019 9 2000 27 EPIGENETIC AND NON-CODING REGULATION OF ALCOHOL ABUSE AND ADDICTION. ALCOHOL USE DISORDER IS A CHRONIC DEBILITATED CONDITION ADVERSELY AFFECTING THE LIVES OF MILLIONS OF INDIVIDUALS THROUGHOUT THE MODERN WORLD. INDIVIDUALS SUFFERING FROM AN ALCOHOL USE DISORDER DIAGNOSIS FREQUENTLY HAVE SERIOUS COOCCURRING CONDITIONS, WHICH OFTEN FURTHER EXACERBATES PROBLEMATIC DRINKING BEHAVIOR. COMPREHENDING THE BIOCHEMICAL PROCESSES UNDERLYING THE PROGRESSION AND PERPETUATION OF DISEASE IS ESSENTIAL FOR MITIGATING MALADAPTIVE BEHAVIOR IN ORDER TO RESTORE BOTH PHYSIOLOGICAL AND PSYCHOLOGICAL HEALTH. THE RANGE OF CELLULAR AND BIOLOGICAL SYSTEMS CONTRIBUTING TO, AND AFFECTED BY, ALCOHOL USE DISORDER AND OTHER COMORBID DISORDERS NECESSITATES A FUNDAMENTAL GRASP OF INTRICATE FUNCTIONAL RELATIONSHIPS THAT GOVERN MOLECULAR BIOLOGY. EPIGENETIC FACTORS ARE RECOGNIZED AS ESSENTIAL MEDIATORS OF CELLULAR BEHAVIOR, ORCHESTRATING A SYMPHONY OF GENE EXPRESSION CHANGES WITHIN MULTICELLULAR ENVIRONMENTS THAT ARE ULTIMATELY RESPONSIBLE FOR DIRECTING HUMAN BEHAVIOR. UNDERSTANDING THE EPIGENETIC AND TRANSCRIPTIONAL REGULATORY MECHANISMS INVOLVED IN THE PATHOGENESIS OF DISEASE IS IMPORTANT FOR IMPROVING AVAILABLE PHARMACOTHERAPIES AND REDUCING THE INCIDENCE OF ALCOHOL ABUSE AND COOCCURRING CONDITIONS. 2021 10 650 22 BISPHENOL A AND HUMAN CHRONIC DISEASES: CURRENT EVIDENCES, POSSIBLE MECHANISMS, AND FUTURE PERSPECTIVES. BISPHENOL-A (BPA) IS ONE OF THE HIGHEST VOLUME CHEMICALS PRODUCED WORLDWIDE, WITH OVER 6BILLION POUNDS PRODUCED AND OVER 100T RELEASED INTO THE ATMOSPHERE EACH YEAR. RECENT EXTENSIVE LITERATURE HAS RAISED CONCERNS ABOUT ITS POSSIBLE IMPLICATION IN THE ETIOLOGY OF SOME HUMAN CHRONIC DISEASES SUCH AS DIABETES, OBESITY, REPRODUCTIVE DISORDERS, CARDIOVASCULAR DISEASES, BIRTH DEFECTS, CHRONIC RESPIRATORY AND KIDNEY DISEASES AND BREAST CANCER. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCES ON THE RELATIONSHIP BETWEEN BPA EXPOSURE AND HUMAN CHRONIC DISEASES AND WE DISCUSS ITS EVENTUAL MECHANISMS OF ACTION, ESPECIALLY GENETIC, EPIGENETIC AND ENDOCRINE DISRUPTION MECHANISMS WITH THE POSSIBLE INVOLVEMENT OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL SIGNALING. 2014 11 436 39 ANTIFRAGILITY AND ANTIINFLAMMAGING: CAN THEY PLAY A ROLE FOR A HEALTHY LONGEVITY? ONE OF THE MOST EXCITING CHALLENGES OF THE RESEARCH ON AGING IS TO EXPLAIN HOW THE ENVIRONMENTAL FACTORS INTERACT WITH THE GENETIC BACKGROUND TO MODULATE THE CHANCES TO REACH THE EXTREME LIMIT OF HUMAN LIFE IN HEALTHY CONDITIONS. THE COMPLEX EPIGENETIC MECHANISMS CAN EXPLAIN BOTH THE INTERACTION BETWEEN DNA AND ENVIRONMENTAL FACTORS, AND THE LONG-DISTANCE PERSISTENCE OF LIFESTYLE EFFECTS, DUE TO THE SO CALLED "EPIGENETIC MEMORY". ONE OF THE MOST EXTENSIVELY INVESTIGATED THEORIES ON AGING FOCUSES ON THE INFLAMMATORY RESPONSES, SUGGESTING THAT THE AGE-RELATED PROGRESSION OF LOW-GRADE AND THEREFORE FOR LONG TIME SUBCLINICAL, CHRONIC, SYSTEMIC, INFLAMMATORY PROCESS, NAMED "INFLAMMAGING", COULD BE THE MOST RELEVANT RISK FACTOR FOR THE DEVELOPMENT AND PROGRESSION OF THE MOST COMMON AGE-RELATED DISEASES AND ULTIMATELY OF DEATH. THE RESULTS OF MANY STUDIES ON LONG-LIVED PEOPLE, ESPECIALLY ON CENTENARIANS, SUGGESTED THAT HEALTHY OLD PEOPLE CAN COPE WITH INFLAMMAGING UPREGULATING THE ANTIINFLAMMAGING RESPONSES. OVERALL, A GENETIC MAKE-UP CODING FOR A STRONG ANTIINFLAMMAGING RESPONSE AND AN AGE-RELATED ABILITY TO REMODEL KEY METABOLIC PATHWAYS TO COPE WITH A PLETHORA OF ANTIGENS AND STRESSORS SEEM TO BE THE BEST WAYS FOR REACH THE EXTREME LIMIT OF HUMAN LIFESPAN IN HEALTH STATUS. IN THIS SCENARIO, WE WONDERED IF THE ANTIFRAGILITY CONCEPT, RECENTLY DEVELOPED IN THE FRAMEWORK OF BUSINESS AND RISK ANALYSIS, COULD ADD SOME INFORMATION TO DISENTANGLE THE HETEROGENEOUS NATURE OF THE AGING PROCESS IN HUMAN. THE ANTIFRAGILITY IS THE PROPERTY OF THE COMPLEX SYSTEMS TO INCREASE THEIR PERFORMANCES BECAUSE OF HIGH STRESS. BASED ON THIS THEORY WE WERE WONDERING IF SOME SUBJECTS COULD BE ABLE TO MODULATE FASTER THAN OTHERS THEIR EPIGENOME TO COPE WITH A PLETHORA OF STRESSORS DURING LIFE, PROBABLY MODULATING THE INFLAMMATORY AND ANTI-INFLAMMATORY RESPONSES. IN THIS FRAMEWORK, ANTIFRAGILITY COULD SHARE SOME COMMON MECHANISMS WITH ANTI-INFLAMMAGING, MODULATING THE ABILITY TO RESTRAIN THE INFLAMMATORY RESPONSES, SO THAT ANTIFRAGILITY AND ANTIINFLAMMAGING COULD BE VIEWED AS DIFFERENT PIECES OF THE SAME PUZZLE, BOTH IMPINGING UPON THE CHANCES TO TRAVEL ALONG THE HEALTHY AGING TRAJECTORY. 2023 12 6350 34 THE ROLE OF EPIGENOMICS IN AQUATIC TOXICOLOGY. OVER THE PAST DECADE, THE FIELD OF MOLECULAR BIOLOGY HAS RAPIDLY INCORPORATED EPIGENETIC STUDIES TO EVALUATE ORGANISM-ENVIRONMENT INTERACTIONS THAT CAN RESULT IN CHRONIC EFFECTS. SUCH RESPONSES ARISE FROM EARLY LIFE STAGE STRESS, THE UTILIZATION OF GENETIC INFORMATION OVER AN INDIVIDUAL'S LIFE TIME, AND TRANSGENERATIONAL INHERITANCE. KNOWLEDGE OF EPIGENETIC MECHANISMS PROVIDES THE POTENTIAL FOR A COMPREHENSIVE EVALUATION OF MULTIGENERATIONAL AND HERITABLE EFFECTS FROM ENVIRONMENTAL STRESSORS, SUCH AS CONTAMINANTS. FOCUSED STUDIES HAVE PROVIDED A GREATER UNDERSTANDING OF HOW MANY RESPONSES TO ENVIRONMENTAL STRESSORS ARE DRIVEN BY EPIGENETIC MODIFIERS. WE DISCUSS THE PROMISE OF EPIGENETICS AND SUGGEST FUTURE RESEARCH DIRECTIONS WITHIN THE FIELD OF AQUATIC TOXICOLOGY, WITH A PARTICULAR FOCUS ON THE POTENTIAL FOR IDENTIFYING KEY HERITABLE MARKS WITH CONSEQUENTIAL IMPACTS AT THE ORGANISM AND POPULATION LEVELS. ENVIRON TOXICOL CHEM 2017;36:2565-2573. (C) 2017 SETAC. 2017 13 2136 38 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019 14 6258 44 THE MOLECULAR MECHANISM OF POLYPHENOLS IN THE REGULATION OF AGEING HALLMARKS. AGEING IS A COMPLEX PROCESS CHARACTERIZED MAINLY BY A DECLINE IN THE FUNCTION OF CELLS, TISSUES, AND ORGANS, RESULTING IN AN INCREASED RISK OF MORTALITY. THIS PROCESS INVOLVES SEVERAL CHANGES, DESCRIBED AS HALLMARKS OF AGEING, WHICH INCLUDE GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL DEPLETION, AND ALTERED INTRACELLULAR COMMUNICATION. THE DETERMINING ROLE THAT ENVIRONMENTAL FACTORS SUCH AS DIET AND LIFESTYLE PLAY ON HEALTH, LIFE EXPECTANCY, AND SUSCEPTIBILITY TO DISEASES, INCLUDING CANCER AND NEURODEGENERATIVE DISEASES, IS WELLESTABLISHED. IN VIEW OF THE GROWING INTEREST IN THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN THE PREVENTION OF CHRONIC DISEASES, SEVERAL STUDIES HAVE BEEN CONDUCTED, AND THEY STRONGLY SUGGEST THAT THE INTAKE OF DIETARY POLYPHENOLS MAY BRING NUMEROUS BENEFITS DUE TO THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES, AND THEIR INTAKE HAS BEEN ASSOCIATED WITH IMPAIRED AGEING IN HUMANS. POLYPHENOL INTAKE HAS BEEN SHOWN TO BE EFFECTIVE IN AMELIORATING SEVERAL AGE-RELATED PHENOTYPES, INCLUDING OXIDATIVE STRESS, INFLAMMATORY PROCESSES, IMPAIRED PROTEOSTASIS, AND CELLULAR SENESCENCE, AMONG OTHER FEATURES, WHICH CONTRIBUTE TO AN INCREASED RISK OF AGEING-ASSOCIATED DISEASES. THIS REVIEW AIMS TO ADDRESS, IN A GENERAL WAY, THE MAIN FINDINGS DESCRIBED IN THE LITERATURE ABOUT THE BENEFITS OF POLYPHENOLS IN EACH OF THE HALLMARKS OF AGEING, AS WELL AS THE MAIN REGULATORY MECHANISMS RESPONSIBLE FOR THE OBSERVED ANTIAGEING EFFECTS. 2023 15 1749 29 EARLY LIFE INTERVENTIONS CAN SHAPE AGING. IT IS WELL DOCUMENTED THAT THE ENVIRONMENT OF THE DEVELOPING FETUS, INCLUDING AVAILABILITY OF NUTRIENTS AND PRESENCE OF TOXINS, CAN HAVE MAJOR IMPACT ON ADULT PHENOTYPE, AGE-RELATED TRAITS AND RISK OF CHRONIC DISEASE. THERE IS ALSO ACCUMULATING EVIDENCE THAT POSTNATAL ENVIRONMENT CAN IMPACT ADULT CHARACTERISTICS RELATED TO EVOLUTIONARY FITNESS, HEALTH, AND AGING. TO DETERMINE WHETHER EARLY LIFE HORMONAL INTERVENTIONS CAN ALTER TRAJECTORY OF AGING, WE HAVE EXAMINED THE EFFECTS OF EARLY LIFE GROWTH HORMONE (GH) REPLACEMENT THERAPY IN PROP1(DF) (AMES DWARF) MICE WHICH ARE GH DEFICIENT AND REMARKABLY LONG LIVED. TWICE-DAILY GH INJECTIONS BETWEEN THE AGES OF TWO AND EIGHT WEEKS COMPLETELY NORMALIZED ("RESCUED") A NUMBER OF ADULT METABOLIC CHARACTERISTICS BELIEVED TO CONTRIBUTE TO EXTENDED LONGEVITY OF THESE MUTANTS. IMPORTANTLY, LONGEVITY OF AMES DWARF MICE WAS REDUCED BY EARLY LIFE GH TREATMENT. THIS WAS ASSOCIATED WITH HISTONE H3 MODIFICATIONS. WE CONCLUDE THAT THE TRAJECTORY OF MAMMALIAN AGING CAN BE MODIFIED BY EARLY LIFE INTERVENTIONS. MECHANISTIC LINKS AMONG INTERVENTIONS DURING POSTNATAL DEVELOPMENT, ADULT METABOLIC CHARACTERISTICS, AGING, AND LONGEVITY, APPARENTLY INVOLVE EPIGENETIC PHENOMENA. 2022 16 5588 37 ROLE OF SENESCENCE IN THE CHRONIC HEALTH CONSEQUENCES OF COVID-19. WHILE THE FULL IMPACT OF COVID-19 IS NOT YET CLEAR, EARLY STUDIES HAVE INDICATED THAT UPWARDS OF 10% OF PATIENTS EXPERIENCE COVID-19 SYMPTOMS LONGER THAN 3 WEEKS, KNOWN AS LONG-HAULER'S SYNDROME OR PACS (POSTACUTE SEQUELAE OF SARS-COV-2 INFECTION). THERE IS LITTLE KNOWN ABOUT RISK FACTORS OR PREDICTORS OF SUSCEPTIBILITY FOR LONG-HAULER'S SYNDROME, BUT OLDER ADULTS ARE AT GREATER RISK FOR SEVERE OUTCOMES AND MORTALITY FROM COVID-19. THE PILLARS OF AGING (INCLUDING CELLULAR SENESCENCE, TELOMERE DYSFUNCTION, IMPAIRED PROTEOSTASIS, MITOCHONDRIAL DYSFUNCTION, DEREGULATED NUTRIENT SENSING, GENOMIC INSTABILITY, PROGENITOR CELL EXHAUSTION, ALTERED INTERCELLULAR COMMUNICATION, AND EPIGENETIC ALTERATIONS) THAT CONTRIBUTE TO AGE-RELATED DYSFUNCTION AND CHRONIC DISEASES (THE "GEROSCIENCE HYPOTHESIS") MAY INTERFERE WITH DEFENSES AGAINST VIRAL INFECTION AND CONSEQUENCES OF THESE INFECTIONS. HEIGHTENING OF THE LOW-GRADE INFLAMMATION THAT IS ASSOCIATED WITH AGING MAY GENERATE AN EXAGGERATED RESPONSE TO AN ACUTE COVID-19 INFECTION. INNATE IMMUNE SYSTEM DYSFUNCTION THAT LEADS TO DECREASED SENESCENT CELL REMOVAL AND/OR INCREASED SENESCENT CELL FORMATION COULD CONTRIBUTE TO ACCUMULATION OF SENESCENT CELLS WITH BOTH AGING AND VIRAL INFECTIONS. THESE PROCESSES MAY CONTRIBUTE TO INCREASED RISK FOR LONG-TERM COVID-19 SEQUELAE IN OLDER OR CHRONICALLY ILL PATIENTS. HENCE, SENOLYTICS AND OTHER GEROSCIENCE INTERVENTIONS THAT MAY PROLONG HEALTHSPAN AND ALLEVIATE CHRONIC DISEASES AND MULTIMORBIDITY LINKED TO FUNDAMENTAL AGING PROCESSES MIGHT BE AN OPTION FOR DELAYING, PREVENTING, OR ALLEVIATING LONG-HAULER'S SYNDROME. 2022 17 1865 38 EMERGING CONCEPTS ON THE ROLE OF EPIGENETICS IN THE RELATIONSHIPS BETWEEN NUTRITION AND HEALTH. UNDERSTANDING THE PHYSIOLOGICAL AND METABOLIC UNDERPINNINGS THAT CONFER INDIVIDUAL DIFFERENCES IN RESPONSES TO DIET AND DIET-RELATED CHRONIC DISEASE IS ESSENTIAL TO ADVANCE THE FIELD OF NUTRITION. THIS INCLUDES ELUCIDATING THE DIFFERENCES IN GENE EXPRESSION THAT ARE MEDIATED THROUGH PROGRAMMING OF THE GENOME THROUGH EPIGENETIC CHROMATIN MODIFICATIONS. EPIGENETIC LANDSCAPES ARE INFLUENCED BY AGE, GENETICS, TOXINS AND OTHER ENVIRONMENTAL FACTORS, INCLUDING DIETARY EXPOSURES AND NUTRITIONAL STATUS. EPIGENETIC MODIFICATIONS INFLUENCE TRANSCRIPTION AND GENOME STABILITY ARE ESTABLISHED DURING DEVELOPMENT WITH LIFE-LONG CONSEQUENCES. THEY CAN BE INHERITED FROM ONE GENERATION TO THE NEXT. THE COVALENT MODIFICATIONS OF CHROMATIN, WHICH INCLUDE METHYLATION AND ACETYLATION, ON DNA NUCLEOTIDE BASES, HISTONE PROTEINS AND RNA ARE DERIVED FROM INTERMEDIATES OF ONE-CARBON METABOLISM AND CENTRAL METABOLISM. THEY INFLUENCE KEY PHYSIOLOGICAL PROCESSES THROUGHOUT LIFE, AND TOGETHER WITH INHERITED DNA PRIMARY SEQUENCE, CONTRIBUTE TO RESPONSIVENESS TO ENVIRONMENTAL STRESSES, DIET AND RISK FOR AGE-RELATED CHRONIC DISEASE. REVEALING DIET-EPIGENETIC RELATIONSHIPS HAS THE POTENTIAL TO TRANSFORM NUTRITION SCIENCE BY INCREASING OUR FUNDAMENTAL UNDERSTANDING OF: (I) THE ROLE OF NUTRIENTS IN BIOLOGICAL SYSTEMS, (II) THE RESILIENCE OF LIVING ORGANISMS IN RESPONDING TO ENVIRONMENTAL PERTURBATIONS, AND (III) THE DEVELOPMENT OF DIETARY PATTERNS THAT PROGRAMME PHYSIOLOGY FOR LIFE-LONG HEALTH. EPIGENETICS MAY ALSO ENABLE THE CLASSIFICATION OF INDIVIDUALS WITH CHRONIC DISEASE FOR SPECIFIC DIETARY MANAGEMENT AND/OR FOR EFFICACIOUS DIET-PHARMACEUTICAL COMBINATION THERAPIES. THESE NEW EMERGING CONCEPTS AT THE INTERFACE OF NUTRITION AND EPIGENETICS WERE DISCUSSED, AND FUTURE RESEARCH NEEDS IDENTIFIED BY LEADING EXPERTS AT THE 26TH MARABOU SYMPOSIUM ENTITLED 'NUTRITION, EPIGENETICS, GENETICS: IMPACT ON HEALTH AND DISEASE'. FOR A COMPILATION OF THE GENERAL DISCUSSION AT THE MARABOU SYMPOSIUM, CLICK HERE HTTP://WWW.MARABOUSYMPOSIUM.ORG/. 2018 18 5359 29 REBOOTING REGULATORY T CELL AND DENDRITIC CELL FUNCTION IN IMMUNE-MEDIATED INFLAMMATORY DISEASES: BIOMARKER AND THERAPY DISCOVERY UNDER A MULTI-OMICS LENS. IMMUNE-MEDIATED INFLAMMATORY DISEASES (IMIDS) ARE A GROUP OF AUTOIMMUNE AND CHRONIC INFLAMMATORY DISORDERS WITH CONSTANTLY INCREASING PREVALENCE IN THE MODERN WORLD. THE VAST MAJORITY OF IMIDS DEVELOP AS A CONSEQUENCE OF COMPLEX MECHANISMS DEPENDENT ON GENETIC, EPIGENETIC, MOLECULAR, CELLULAR, AND ENVIRONMENTAL ELEMENTS, THAT LEAD TO DEFECTS IN IMMUNE REGULATORY GUARDIANS OF TOLERANCE, SUCH AS DENDRITIC (DCS) AND REGULATORY T (TREGS) CELLS. AS A RESULT OF THIS DYSFUNCTION, IMMUNE TOLERANCE COLLAPSES AND PATHOGENESIS EMERGES. DEEPER UNDERSTANDING OF SUCH DISEASE DRIVING MECHANISMS REMAINS A MAJOR CHALLENGE FOR THE PREVENTION OF INFLAMMATORY DISORDERS. THE RECENT RENAISSANCE IN HIGH THROUGHPUT TECHNOLOGIES HAS ENABLED THE INCREASE IN THE AMOUNT OF DATA COLLECTED THROUGH MULTIPLE OMICS LAYERS, WHILE ADDITIONALLY NARROWING THE RESOLUTION DOWN TO THE SINGLE CELL LEVEL. IN LIGHT OF THE AFOREMENTIONED, THIS REVIEW FOCUSES ON DCS AND TREGS AND DISCUSSES HOW MULTI-OMICS APPROACHES CAN BE HARNESSED TO CREATE ROBUST CELL-BASED IMID BIOMARKERS IN HOPE OF LEADING TO MORE EFFICIENT AND PATIENT-TAILORED THERAPEUTIC INTERVENTIONS. 2022 19 2616 26 EPIGENOME MODULATION INDUCED BY KETOGENIC DIETS. KETOGENIC DIETS (KD) ARE DIETARY STRATEGIES LOW IN CARBOHYDRATES, NORMAL IN PROTEIN, AND HIGH, NORMAL, OR REDUCED IN FAT WITH OR WITHOUT (VERY LOW-CALORIES KETOGENIC DIET, VLCKD) A REDUCED CALORIC INTAKE. KDS HAVE BEEN SHOWN TO BE USEFUL IN THE TREATMENT OF OBESITY, METABOLIC DISEASES AND RELATED DISORDERS, NEUROLOGICAL DISEASES, AND VARIOUS PATHOLOGICAL CONDITIONS SUCH AS CANCER, NONALCOHOLIC LIVER DISEASE, AND CHRONIC PAIN. SEVERAL STUDIES HAVE INVESTIGATED THE INTRACELLULAR METABOLIC PATHWAYS THAT CONTRIBUTE TO THE BENEFICIAL EFFECTS OF THESE DIETS. ALTHOUGH EPIGENETIC CHANGES ARE AMONG THE MOST IMPORTANT DETERMINANTS OF AN ORGANISM'S ABILITY TO ADAPT TO ENVIRONMENTAL CHANGES, DATA ON THE EPIGENETIC CHANGES ASSOCIATED WITH THESE DIETARY PATHWAYS ARE STILL LIMITED. THIS REVIEW PROVIDES AN OVERVIEW OF THE MAJOR EPIGENETIC CHANGES ASSOCIATED WITH KDS. 2022 20 3777 23 INTERACTOME OF OBESITY: OBESIDOME : GENETIC OBESITY, STRESS INDUCED OBESITY, PATHOGENIC OBESITY INTERACTION. OBESITY IS A CHRONIC DISEASE OF INCREASING PREVALENCE REACHING EPIDEMIC PROPORTIONS. GENETIC DEFECTS AS WELL AS EPIGENETIC EFFECTS CONTRIBUTE TO THE OBESITY PHENOTYPE. INVESTIGATING GENE (E.G. MC4R DEFECTS)-ENVIRONMENT (BEHAVIOR, INFECTIOUS AGENTS, STRESS) INTERACTIONS IS A RELATIVE NEW FIELD OF GREAT RESEARCH INTEREST. IN THIS STUDY, WE HAVE MADE AN EFFORT TO CREATE AN INTERACTOME (HENCEFORTH REFERRED TO AS "OBESIDOME"), WHERE EXTRINSIC STRESSORS RESPONSE, INTRINSIC PREDISPOSITION, IMMUNITY RESPONSE TO INFLAMMATION AND AUTONOMOUS NERVOUS SYSTEM IMPLICATIONS ARE INTEGRATED. THESE PATHWAYS ARE PRESENTED IN ONE INTERACTOME NETWORK FOR THE FIRST TIME. IN OUR STUDY, OBESITY-RELATED GENES/GENE PRODUCTS WERE FOUND TO FORM A COMPLEX INTERACTIONS NETWORK. 2017