1 3116 133 GEROSCIENCE: ADDRESSING THE MISMATCH BETWEEN ITS EXCITING RESEARCH OPPORTUNITIES, ITS ECONOMIC IMPERATIVE AND ITS CURRENT FUNDING CRISIS. THERE IS AT PRESENT A HUGE DISCONNECT BETWEEN LEVELS OF FUNDING FOR BASIC RESEARCH ON FUNDAMENTAL MECHANISMS OF BIOLOGICAL AGING AND, GIVEN DEMOGRAPHIC PROJECTIONS, THE ANTICIPATED ENORMOUS SOCIAL AND ECONOMIC IMPACTS OF A LITANY OF CHRONIC DISEASES FOR WHICH AGING IS BY FAR THE MAJOR RISK FACTOR: ONE VALUABLE APPROACH, RECENTLY INSTIGATED BY FELIPE SIERRA & COLLEAGUES AT THE US NATIONAL INSTITUTE ON AGING, IS THE DEVELOPMENT OF A GEROSCIENCE INTEREST GROUP AMONG VIRTUALLY ALL OF THE NIH INSTITUTES. A COMPLEMENTARY APPROACH WOULD BE TO SEEK MAJOR ESCALATIONS OF PRIVATE FUNDING. THE AMERICAN FEDERATION FOR AGING RESEARCH, THE PAUL GLENN FOUNDATION AND THE ELLISON MEDICAL FOUNDATION PIONEERED EFFORTS BY THE PRIVATE SECTOR TO PROVIDE SUBSTANTIAL SUPPLEMENTS TO PUBLIC SOURCES OF FUNDING. IT IS TIME FOR OUR COMMUNITY TO ORGANIZE EFFORTS TOWARDS THE ENHANCEMENTS OF SUCH CRUCIAL CONTRIBUTIONS, ESPECIALLY IN SUPPORT OF THE EMERGING GENERATION OF YOUNG INVESTIGATORS, MANY OF WHOM ARE LEAVING OUR RANKS TO SEEK ALTERNATIVE EMPLOYMENT. TO DO SO, WE MUST PROVIDE POTENTIAL DONORS WITH STRONG ECONOMIC, HUMANITARIAN AND SCIENTIFIC RATIONALES. AN INITIAL APPROACH TO SUCH EFFORTS IS BRIEFLY OUTLINED IN THIS MANUSCRIPT AS A BASIS FOR WIDER DISCUSSIONS WITHIN OUR COMMUNITY. 2017 2 4871 31 OUR GENES ARE NOT OUR DESTINY: INCORPORATING MOLECULAR MEDICINE INTO CLINICAL PRACTICE. IN MANY DEVELOPED NATIONS, THE STATE OF PUBLICLY ADMINISTERED HEALTH CARE IS INCREASINGLY PRECARIOUS AS A RESULT OF ESCALATING NUMBERS OF CHRONICALLY ILL PATIENTS, INADEQUATE MEDICAL PERSONNEL AND HOSPITAL FACILITIES, AS WELL AS SPARSE FUNDING FOR ONGOING UPGRADES TO STATE-OF-THE-ART DIAGNOSTIC AND THERAPEUTIC TECHNOLOGY - AN INCREASED EMPHASIS ON AETIOLOGY-CENTRED MEDICINE SHOULD BE CONSIDERED IN ORDER TO ACHIEVE IMPROVED HEALTH FOR PATIENTS AND POPULATIONS. MEDICAL PRACTICE PATTERNS WHICH ARE DESIGNED TO PROVIDE QUICK AND EFFECTIVE AMELIORATION OF SIGNS AND SYMPTOMS ARE FREQUENTLY NOT AN ENDURING SOLUTION TO MANY HEALTH AFFLICTIONS AND CHRONIC DISEASE STATES. RECENT SCIENTIFIC DISCOVERY HAS RENDERED THE DRUG-ORIENTED ALGORITHMIC PARADIGM COMMONLY FOUND IN CONTEMPORARY EVIDENCE-BASED MEDICINE TO BE A REDUCTIONIST APPROACH TO CLINICAL PRACTICE. UNFOLDING EVIDENCE APPEARS TO SUPPORT A GENETIC PREDISPOSITION MODEL OF HEALTH AND ILLNESS RATHER THAN A FATALISTIC PREDESTINATION CONSTRUCT - MODIFIABLE EPIGENETIC AND ENVIRONMENTAL FACTORS HAVE ENORMOUS POTENTIAL TO INFLUENCE CLINICAL OUTCOMES. BY UNDERSTANDING AND APPLYING FUNDAMENTAL CLINICAL PRINCIPLES RELATING TO THE EMERGING FIELDS OF MOLECULAR MEDICINE, NUTRIGENOMICS AND HUMAN EXPOSURE ASSESSMENT, DOCTORS WILL BE EMPOWERED TO ADDRESS CAUSALITY OF AFFLICTION WHEN POSSIBLE AND ACHIEVE SUSTAINED REPRIEVE FOR MANY SUFFERING PATIENTS. 2008 3 421 28 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 4 1377 26 DEVELOPMENTAL PROGRAMMING: STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS-SUMMARY FROM A PENNINGTON BIOMEDICAL SYMPOSIUM. OBJECTIVE: ON DECEMBER 8-9, 2014, THE PENNINGTON BIOMEDICAL RESEARCH CENTER CONVENED A SCIENTIFIC SYMPOSIUM TO REVIEW THE STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS FOR THE STUDY OF DEVELOPMENTAL PROGRAMMING OF OBESITY AND CHRONIC DISEASE. THE OBJECTIVES OF THE SYMPOSIUM WERE TO DISCUSS: (I) PAST AND CURRENT SCIENTIFIC ADVANCES IN ANIMAL MODELS, POPULATION-BASED COHORT STUDIES, AND HUMAN CLINICAL TRIALS, (II) THE STATE-OF-THE-SCIENCE OF EPIGENETIC-BASED RESEARCH, AND (III) CONSIDERATIONS FOR FUTURE STUDIES. RESULTS: THIS SYMPOSIUM PROVIDED A COMPREHENSIVE ASSESSMENT OF THE STATE OF THE SCIENTIFIC FIELD AND IDENTIFIED RESEARCH GAPS AND OPPORTUNITIES FOR FUTURE RESEARCH IN ORDER TO UNDERSTAND THE MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF HEALTH AND DISEASE. CONCLUSIONS: IDENTIFYING THE MECHANISMS WHICH CAUSE OR CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF FUTURE GENERATIONS WILL BE INVALUABLE TO THE SCIENTIFIC AND MEDICAL COMMUNITY. THE ABILITY TO INTERVENE DURING CRITICAL PERIODS OF PRENATAL AND EARLY POSTNATAL LIFE TO PROMOTE LIFELONG HEALTH IS THE ULTIMATE GOAL. CONSIDERATIONS FOR FUTURE RESEARCH INCLUDING THE USE OF ANIMAL MODELS, THE STUDY DESIGN IN HUMAN COHORTS WITH CONSIDERATIONS ABOUT THE TIMING OF THE INTRAUTERINE EXPOSURE, AND THE RESULTING TISSUE-SPECIFIC EPIGENETIC SIGNATURE WERE EXTENSIVELY DISCUSSED AND ARE PRESENTED IN THIS MEETING SUMMARY. 2016 5 627 27 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 6 2521 27 EPIGENETICS AND THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH MODEL: BRIDGING NATURE, NURTURE, AND PATIENT-CENTERED POPULATION HEALTH. EPIGENETIC PROCESSES ENABLE ENVIRONMENTAL INPUTS SUCH AS DIET, EXERCISE, AND HEALTH BEHAVIORS TO REVERSIBLY TAG DNA WITH CHEMICAL "MARKS" THAT INCREASE OR DECREASE THE EXPRESSION OF AN INDIVIDUAL'S GENETIC TEMPLATE. OVER TIME, EPIGENETIC ADAPTATIONS ENABLE THE EFFECTS OF HEALTHY OR UNHEALTHY STRESSES TO BECOME STABLY EXPRESSED IN THE TISSUE OF AN ORGANISM, WITH IMPORTANT CONSEQUENCES FOR HEALTH AND DISEASE. NEW RESEARCH INDICATES THAT SEEMINGLY NON-BIOLOGICAL FACTORS SUCH AS SOCIAL STRESS, POVERTY, AND CHILDHOOD HARDSHIP INITIATE EPIGENETIC ADAPTATIONS IN GENE PATHWAYS THAT GOVERN INFLAMMATION AND IMMUNITY, TWO OF THE GREATEST CONTRIBUTORS TO CHRONIC DISEASES SUCH AS DIABETES AND OBESITY. EPIGENETIC PROCESSES THEREFORE PROVIDE A BIOLOGICAL BRIDGE BETWEEN THE GENOME-AN INDIVIDUAL'S GENETIC INHERITANCE-AND THE SOCIAL DETERMINANTS OF HEALTH-THE CONDITIONS IN WHICH THEY ARE BORN, GROW, LIVE, WORK, AND AGE. THIS PERSPECTIVE PAPER ARGUES THAT PHYSICAL THERAPY CLINICIANS, RESEARCHERS, AND EDUCATORS CAN USE THE THEORETICAL FRAMEWORK PROVIDED BY THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY, AND HEALTH (ICF MODEL) TO HARMONIZE NEW DISCOVERIES FROM BOTH PUBLIC HEALTH RESEARCH AND MEDICALLY FOCUSED GENOMIC RESEARCH. THE ICF MODEL LIKEWISE CAPTURES THE ESSENTIAL ROLE PLAYED BY PHYSICAL ACTIVITY AND EXERCISE, WHICH INITIATE POWERFUL AND WIDESPREAD EPIGENETIC ADAPTATIONS THAT PROMOTE HEALTH AND FUNCTIONING. IN THIS PROPOSED FRAMEWORK, EPIGENETIC PROCESSES TRANSDUCE THE EFFECTS OF THE SOCIAL DETERMINANTS OF HEALTH AND BEHAVIORS SUCH AS EXERCISE INTO STABLE BIOLOGICAL ADAPTATIONS THAT AFFECT AN INDIVIDUAL'S DAILY ACTIVITIES AND THEIR PARTICIPATION IN SOCIAL ROLES. BY HARMONIZING "NATURE" AND "NURTURE," PHYSICAL THERAPISTS CAN APPROACH PATIENT CARE WITH A MORE INTEGRATED PERSPECTIVE, CAPITALIZING ON NOVEL DISCOVERIES IN PRECISION MEDICINE, REHABILITATION SCIENCE, AND IN POPULATION-LEVEL RESEARCH. AS THE EXPERTS IN PHYSICAL ACTIVITY AND EXERCISE, PHYSICAL THERAPISTS ARE IDEALLY POSITIONED TO DRIVE PROGRESS IN THE NEW ERA OF PATIENT-CENTERED POPULATION HEALTH CARE. 2022 7 705 24 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 8 28 29 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 9 2136 35 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 10 13 38 360-DEGREE PERSPECTIVES ON OBESITY. ALARMING STATISTICS SHOW THAT THE NUMBER OF PEOPLE AFFECTED BY EXCESSIVE WEIGHT HAS SURPASSED 2 BILLION, REPRESENTING APPROXIMATELY 30% OF THE WORLD'S POPULATION. THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF ONE OF THE MOST SERIOUS PUBLIC HEALTH PROBLEMS, CONSIDERING THAT OBESITY REQUIRES AN INTEGRATIVE APPROACH THAT TAKES INTO ACCOUNT ITS COMPLEX ETIOLOGY, INCLUDING GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. ONLY AN UNDERSTANDING OF THE CONNECTIONS BETWEEN THE MANY CONTRIBUTORS TO OBESITY AND THE SYNERGY BETWEEN TREATMENT INTERVENTIONS CAN ENSURE SATISFACTORY OUTCOMES IN REDUCING OBESITY. MECHANISMS SUCH AS OXIDATIVE STRESS, CHRONIC INFLAMMATION, AND DYSBIOSIS PLAY A CRUCIAL ROLE IN THE PATHOGENESIS OF OBESITY AND ITS ASSOCIATED COMPLICATIONS. COMPOUNDING FACTORS SUCH AS THE DELETERIOUS EFFECTS OF STRESS, THE NOVEL CHALLENGE POSED BY THE OBESOGENIC DIGITAL (FOOD) ENVIRONMENT, AND THE STIGMA ASSOCIATED WITH OBESITY SHOULD NOT BE OVERLOOKED. PRECLINICAL RESEARCH IN ANIMAL MODELS HAS BEEN INSTRUMENTAL IN ELUCIDATING THESE MECHANISMS, AND TRANSLATION INTO CLINICAL PRACTICE HAS PROVIDED PROMISING THERAPEUTIC OPTIONS, INCLUDING EPIGENETIC APPROACHES, PHARMACOTHERAPY, AND BARIATRIC SURGERY. HOWEVER, MORE STUDIES ARE NECESSARY TO DISCOVER NEW COMPOUNDS THAT TARGET KEY METABOLIC PATHWAYS, INNOVATIVE WAYS TO DELIVER THE DRUGS, THE OPTIMAL COMBINATIONS OF LIFESTYLE INTERVENTIONS WITH ALLOPATHIC TREATMENTS, AND, LAST BUT NOT LEAST, EMERGING BIOLOGICAL MARKERS FOR EFFECTIVE MONITORING. WITH EACH PASSING DAY, THE OBESITY CRISIS TIGHTENS ITS GRIP, THREATENING NOT ONLY INDIVIDUAL LIVES BUT ALSO BURDENING HEALTHCARE SYSTEMS AND SOCIETIES AT LARGE. IT IS HIGH TIME WE TOOK ACTION AS WE CONFRONT THE URGENT IMPERATIVE TO ADDRESS THIS ESCALATING GLOBAL HEALTH CHALLENGE HEAD-ON. 2023 11 2528 24 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 12 49 28 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 13 3007 22 GENETIC, IMMUNOLOGIC, AND ENVIRONMENTAL BASIS OF SARCOIDOSIS. SARCOIDOSIS IS A MULTISYSTEM DISEASE WITH TREMENDOUS HETEROGENEITY IN DISEASE MANIFESTATIONS, SEVERITY, AND CLINICAL COURSE THAT VARIES AMONG DIFFERENT ETHNIC AND RACIAL GROUPS. TO BETTER UNDERSTAND THIS DISEASE AND TO IMPROVE THE OUTCOMES OF PATIENTS, A NATIONAL HEART, LUNG, AND BLOOD INSTITUTE WORKSHOP WAS CONVENED TO ASSESS THE CURRENT STATE OF KNOWLEDGE, GAPS, AND RESEARCH NEEDS ACROSS THE CLINICAL, GENETIC, ENVIRONMENTAL, AND IMMUNOLOGIC ARENAS. WE ALSO EXPLORED TO WHAT EXTENT THE INTERPLAY OF THE GENETIC, ENVIRONMENTAL, AND IMMUNOLOGIC FACTORS COULD EXPLAIN THE DIFFERENT PHENOTYPES AND OUTCOMES OF PATIENTS WITH SARCOIDOSIS, INCLUDING THE CHRONIC PHENOTYPES THAT HAVE THE GREATEST HEALTHCARE BURDEN. THE POTENTIAL USE OF CURRENT GENETIC, EPIGENETIC, AND IMMUNOLOGIC TOOLS ALONG WITH STUDY APPROACHES THAT INTEGRATE ENVIRONMENTAL EXPOSURES AND PRECISE CLINICAL PHENOTYPING WERE ALSO EXPLORED. FINALLY, WE MADE EXPERT PANEL-BASED CONSENSUS RECOMMENDATIONS FOR RESEARCH APPROACHES AND PRIORITIES TO IMPROVE OUR UNDERSTANDING OF THE EFFECT OF THESE FACTORS ON THE HEALTH OUTCOMES IN SARCOIDOSIS. 2017 14 6459 20 TIME TO CHANGE FROM A SIMPLE LINEAR MODEL TO A COMPLEX SYSTEMS MODEL. A SIMPLE LINEAR MODEL TO TEST THE HYPOTHESIS BASED ON ONE-ON-ONE RELATIONSHIP HAS BEEN USED TO FIND THE CAUSATIVE FACTORS OF DISEASES. HOWEVER, WE NOW KNOW THAT NOT JUST ONE, BUT MANY FACTORS FROM DIFFERENT SYSTEMS SUCH AS CHEMICAL EXPOSURE, GENES, EPIGENETIC CHANGES, AND PROTEINS ARE INVOLVED IN THE PATHOGENESIS OF CHRONIC DISEASES SUCH AS DIABETES MELLITUS. SO, WITH AVAILABILITY OF MODERN TECHNOLOGIES TO UNDERSTAND THE INTRICATE NATURE OF RELATIONS AMONG COMPLEX SYSTEMS, WE NEED TO MOVE FORWARD TO THE FUTURE BY TAKING COMPLEX SYSTEMS MODEL. 2016 15 456 25 APPLYING A LIFE COURSE BIOLOGICAL AGE FRAMEWORK TO IMPROVING THE CARE OF INDIVIDUALS WITH ADULT CANCERS: REVIEW AND RESEARCH RECOMMENDATIONS. IMPORTANCE: THE PRACTICE OF ONCOLOGY WILL INCREASINGLY INVOLVE THE CARE OF A GROWING POPULATION OF INDIVIDUALS WITH MIDLIFE AND LATE-LIFE CANCERS. MANAGING CANCER IN THESE INDIVIDUALS IS COMPLEX, BASED ON DIFFERENCES IN BIOLOGICAL AGE AT DIAGNOSIS. BIOLOGICAL AGE IS A MEASURE OF ACCUMULATED LIFE COURSE DAMAGE TO BIOLOGICAL SYSTEMS, LOSS OF RESERVE, AND VULNERABILITY TO FUNCTIONAL DETERIORATION AND DEATH. BIOLOGICAL AGE IS IMPORTANT BECAUSE IT AFFECTS THE ABILITY TO MANAGE THE RIGORS OF CANCER THERAPY, SURVIVORS' FUNCTION, AND CANCER PROGRESSION. HOWEVER, BIOLOGICAL AGE IS NOT ALWAYS CLINICALLY APPARENT. THIS REVIEW PRESENTS A CONCEPTUAL FRAMEWORK OF LIFE COURSE BIOLOGICAL AGING, SUMMARIZES CANDIDATE MEASURES, AND DESCRIBES A RESEARCH AGENDA TO FACILITATE CLINICAL TRANSLATION TO ONCOLOGY PRACTICE. OBSERVATIONS: MIDLIFE AND LATE-LIFE CANCERS ARE CHRONIC DISEASES THAT MAY ARISE FROM CUMULATIVE PATTERNS OF BIOLOGICAL AGING OCCURRING OVER THE LIFE COURSE. BEFORE DIAGNOSIS, EACH NEW PATIENT WAS ON A DISTINCT COURSE OF BIOLOGICAL AGING RELATED TO PAST EXPOSURES, LIFE EXPERIENCES, GENETICS, AND NONCANCER CHRONIC DISEASE. CANCER AND ITS TREATMENTS MAY ALSO BE ASSOCIATED WITH BIOLOGICAL AGING. SEVERAL MEASURES OF BIOLOGICAL AGE, INCLUDING P16INK4A, EPIGENETIC AGE, TELOMERE LENGTH, AND INFLAMMATORY AND BODY COMPOSITION MARKERS, HAVE BEEN USED IN ONCOLOGY RESEARCH. ONE OR MORE OF THESE MEASURES MAY BE USEFUL IN CANCER CARE, EITHER ALONE OR IN COMBINATION WITH CLINICAL HISTORY AND GERIATRIC ASSESSMENTS. HOWEVER, FURTHER RESEARCH WILL BE NEEDED BEFORE BIOLOGICAL AGE ASSESSMENT CAN BE RECOMMENDED IN ROUTINE PRACTICE, INCLUDING DETERMINATION OF SITUATIONS IN WHICH KNOWLEDGE ABOUT BIOLOGICAL AGE WOULD CHANGE TREATMENT, ASCERTAINING WHETHER TREATMENT EFFECTS ON BIOLOGICAL AGING ARE SHORT-LIVED OR PERSISTENT, AND TESTING INTERVENTIONS TO MODIFY BIOLOGICAL AGE, DECREASE TREATMENT TOXIC EFFECTS, AND MAINTAIN FUNCTIONAL ABILITIES. CONCLUSIONS AND RELEVANCE: UNDERSTANDING DIFFERENCES IN BIOLOGICAL AGING COULD ULTIMATELY ALLOW CLINICIANS TO BETTER PERSONALIZE TREATMENT AND SUPPORTIVE CARE, DEVELOP TAILORED SURVIVORSHIP CARE PLANS, AND PRESCRIBE PREVENTIVE OR AMELIORATIVE THERAPIES AND BEHAVIORS INFORMED BY AGING MECHANISMS. 2021 16 4156 27 MECHANOBIOLOGY AND ADAPTIVE PLASTICITY THEORY AS A POTENTIAL CONFOUNDING FACTOR IN PREDICTING MUSCULOSKELETAL FOOT FUNCTION. THERE ARE MANY THEORETICAL MODELS THAT ATTEMPT TO ACCURATELY AND CONSISTENTLY LINK KINEMATIC AND KINETIC INFORMATION TO MUSCULOSKELETAL PAIN AND DEFORMITY OF THE FOOT. BIOMECHANICAL THEORY OF THE FOOT LACKS A CONSENSUAL MODEL: CLINICIANS ARE ENTICED TO DRAW FROM NUMEROUS PARADIGMS, EACH HAVING DIFFERENT LEVELS OF SUPPORTIVE EVIDENCE AND CONTRASTING METHODS OF EVALUATION, IN ORDER TO ENGAGE IN CLINICAL DEDUCTION AND TREATMENT PLANNING. CONTRIVING TO FIND A LINK BETWEEN FORM AND FUNCTION LIES AT THE HEART OF MOST OF THESE COMPETING THEORIES AND THE PHYSICAL NATURE OF THE DISCIPLINE HAS PROMPTED AN ENGINEERING APPROACH. PHYSICS IS OF GREAT IMPORTANCE IN BIOLOGY AND HELPS US TO MODEL THE FORCES THAT THE FOOT HAS TO DEAL WITH IN ORDER FOR IT TO WORK EFFECTIVELY. HOWEVER, THE TISSUES OF THE BODY HAVE COMPLEX PROCESSES THAT ARE IN PLACE TO PROTECT THEM AND THEY ARE VARIABLE BETWEEN INDIVIDUALS. RESEARCH IS UNCOVERING WHY THESE DIFFERENCES EXIST AND HOW THESE PROCESSES ARE GOVERNED. THE EMERGING EXPLANATIONS FOR ADAPTABILITY OF FOOT STRUCTURE AND MUSCULOSKELETAL HOMEOSTASIS OFFER NEW INSIGHTS INTO HOW CLINICAL VARIATION IN OUTCOMES AND TREATMENT EFFECTS MIGHT ARISE. THESE BIOLOGICAL PROCESSES UNDERLIE HOW VARIATION IN THE PERFORMANCE AND USE OF COMMON TRAITS, EVEN WITHIN APPARENTLY SIMILAR SUBGROUPS, MAKE ANATOMICAL DISTINCTION LESS MEANINGFUL AND ARE LIKELY TO UNDERMINE THE JUSTIFICATION OF A "FOOT TYPE." FURTHERMORE, MECHANOBIOLOGY INTRODUCES A PROBABILISTIC ELEMENT TO MORPHOLOGY BASED ON GENETIC AND EPIGENETIC FACTORS. 2021 17 1248 29 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 18 2919 20 GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS DEFINING LIPID-RELATED TRAITS. PURPOSE OF REVIEW: STEPS TOWARDS REDUCING CHRONIC DISEASE PROGRESSION ARE CONTINUOUSLY BEING TAKEN THROUGH THE FORM OF GENOMIC RESEARCH. STUDIES OVER THE LAST YEAR HAVE HIGHLIGHTED MORE AND MORE POLYMORPHISMS, PATHWAYS AND INTERACTIONS RESPONSIBLE FOR METABOLIC DISORDERS SUCH AS CARDIOVASCULAR DISEASE, OBESITY AND DYSLIPIDEMIA. RECENT FINDINGS: MANY OF THESE CHRONIC ILLNESSES CAN BE PARTIALLY BLAMED BY ALTERED LIPID METABOLISM, COMBINED WITH INDIVIDUAL GENETIC COMPONENTS. CRITICAL EVALUATION AND COMPARISON OF THESE RECENT STUDIES IS ESSENTIAL IN ORDER TO COMPREHEND THE RESULTS, CONCLUSIONS AND FUTURE PROSPECTS IN THE FIELD OF GENOMICS AS A WHOLE. RECENT LITERATURE ELUCIDATES SIGNIFICANT GENE--DIET AND GENE--ENVIRONMENT INTERACTIONS RESULTING IN ALTERED LIPID METABOLISM, INFLAMMATION AND OTHER METABOLIC IMBALANCES LEADING TO CARDIOVASCULAR DISEASE AND OBESITY. SUMMARY: EPIGENETIC AND EPISTATIC INTERACTIONS ARE NOW BECOMING MORE SIGNIFICANTLY ASSOCIATED WITH SUCH DISORDERS, AS GENOMIC RESEARCH DIGS DEEPER INTO THE COMPLEX NATURE OF GENETIC INDIVIDUALITY AND HERITABILITY. THE VAST ARRAY OF DATA COLLECTED FROM GENOME-WIDE ASSOCIATION STUDIES MUST NOW BE EMPOWERED AND EXPLORED THROUGH MORE COMPLEX INTERACTION STUDIES, USING STANDARDIZED METHODS AND LARGER SAMPLE SIZES. IN DOING SO THE ETIOLOGY OF CHRONIC DISEASE PROGRESSION WILL BE FURTHER UNDERSTOOD. 2011 19 114 32 A SOCIO-BIOLOGICAL EXPLANATION FOR SOCIAL DISPARITIES IN NON-COMMUNICABLE CHRONIC DISEASES: THE PRODUCT OF HISTORY? THIS STUDY PLACES SOCIAL DISPARITIES IN THE MAJOR NON-COMMUNICABLE CHRONIC DISEASES WITHIN THEIR GLOBAL ECONOMIC AND HISTORICAL CONTEXTS. RAPID ECONOMIC TRANSITION OUTSIDE THE DEVELOPED WORLD PROVIDES A UNIQUE OPPORTUNITY TO RE-EXAMINE THE ORIGINS OF, AND BIOLOGICAL MECHANISMS DRIVING, SOCIAL DISPARITIES. GAPS IN PREVAILING THEORIES FOCUSING ON MATERIAL RESOURCES, CIVIC INFRASTRUCTURE AND SOCIAL STRUCTURE ARE IDENTIFIED. USING LONGSTANDING EXPERIMENTAL EVIDENCE AND EPIGENETIC THEORIES, IT IS SUGGESTED THAT EXPOSURE TO ECONOMIC DEVELOPMENT OVER GENERATIONS (IE, IMPROVED LIVING CONDITIONS OVER HISTORICAL TIME) COULD BY ACTING ON DIFFERENT BIOLOGICAL AXES (SOMATOTROPHIC AND GONADOTROPHIC) GENERATE SPECIFIC PATTERNS OF SOCIAL DISPARITIES. MOREOVER, THESE SAME PROCESSES COULD INITIALLY GENERATE A TRANSIENT EPIDEMIC OF DIABETES AS WELL AS A PERMANENT INCREASE IN MALE RISK OF PREMATURE ISCHAEMIC HEART DISEASE. AS SUCH, THIS STUDY DEMONSTRATES THE IMPORTANCE OF CONTEXT, AND IMPLIES THAT CURRENT EVIDENCE FROM THE DEVELOPED WORLD MAY BE LARGELY UNINFORMATIVE FOR PREVENTING OR MITIGATING SOCIAL DISPARITIES IN NON-COMMUNICABLE CHRONIC DISEASES ELSEWHERE, SUGGESTING RESEARCH EFFORTS SHOULD BE FOCUSED ON DEVELOPING COUNTRIES. 2010 20 1386 35 DIABETES: AN UPDATE ON THE PANDEMIC AND POTENTIAL SOLUTIONS. DIABETES MELLITUS IS A CHRONIC METABOLIC DISEASE WITH DEADLY, DISABLING, AND COSTLY CONSEQUENCES FOR INDIVIDUALS, FAMILIES, COMMUNITIES, AND COUNTRIES. ALTHOUGH THEY ARE PHENOTYPICALLY DISTINCT, DIABETES SUBTYPES (TYPE 1, TYPE 2, GESTATIONAL, AND OTHER FORMS) ARE ALL DEFINED BY ELEVATED BLOOD GLUCOSE LEVELS. APPROXIMATELY 95 PERCENT OF DIABETES CASES WORLDWIDE ARE TYPE 2 DIABETES (PREVIOUSLY KNOWN AS ADULT-ONSET OR NON-INSULIN-DEPENDENT DIABETES), WHICH IS THE FOCUS OF THIS CHAPTER. TYPE 1 DIABETES (PREVIOUSLY KNOWN AS INSULIN-DEPENDENT DIABETES) MOST COMMONLY BEGINS IN CHILDHOOD AND ADOLESCENCE. GESTATIONAL DIABETES REFERS TO ELEVATED BLOOD GLUCOSE LEVELS DURING PREGNANCY AMONG WOMEN WITHOUT PREVIOUS DIABETES AND IS ASSOCIATED WITH FETAL, BIRTHING, AND EARLY CHILDHOOD COMPLICATIONS AS WELL AS HIGHER RISK OF THE MOTHER DEVELOPING POSTGESTATION DIABETES. THE GROWTH OF DIABETES AND ITS IMPACTS HAVE ACCELERATED WORLDWIDE SINCE THE END OF THE TWENTIETH CENTURY (NCD-RISC 2016), LIKELY CORRELATED WITH EXPANSION OF DIABETES RISK FACTORS, ESPECIALLY POPULATION AGING AND OBESITY. DIABETES IS A MULTIFACTORIAL CONDITION. BECAUSE GENETIC, EPIGENETIC, LIFESTYLE, ECONOMIC, AND PSYCHOSOCIAL FACTORS ALL CONTRIBUTE TO THE DEVELOPMENT OF DIABETES (MCCARTHY 2010; STUMVOLL, GOLDSTEIN, AND VAN HAEFTEN 2005), PREVENTING AND MANAGING THE CONDITION REQUIRE ACTION AT POLICY, PROGRAM, CLINICAL PRACTICE, AND INDIVIDUAL LEVELS (HILL AND OTHERS 2013). RELIABLE AND MEANINGFUL ESTIMATES OF BURDENS, RISK FACTORS, AND EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS AS WELL AS EVALUATIONS OF EXISTING POLICIES, ARE LIMITED; DATA ARE ESPECIALLY SCARCE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS). THIS CHAPTER FOCUSES ON WHAT CAN AND SHOULD BE DONE TO ADDRESS DIABETES. WE PRESENT THE AVAILABLE DATA REGARDING GLOBAL BURDENS AND TRENDS IN DIABETES; REVIEW AVAILABLE EVIDENCE AND ASSESS THE EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS TO PREVENT, DETECT, AND CONTROL DIABETES; AND REPORT SUMMARY EXPERT OPINIONS REGARDING THE PRIORITY AND FEASIBILITY OF IMPLEMENTING THESE INTERVENTIONS. ASSIMILATING EVIDENCE FROM COUNTRIES AT DIFFERENT INCOME LEVELS, WE PROVIDE GLOBAL PERSPECTIVES ON THE DIABETES PANDEMIC, RECOMMEND PRIORITY INTERVENTIONS, AND IDENTIFY REMAINING DATA GAPS. 2017