1 792 138 CELLULAR MECHANISMS PROMOTING CACHEXIA AND HOW THEY ARE OPPOSED BY SIRTUINS (1). MANY CHRONIC DISEASES ARE ASSOCIATED WITH UNINTENTIONAL LOSS OF BODY WEIGHT, WHICH IS TERMED "CACHEXIA". CACHEXIA IS A COMPLEX MULTIFACTORIAL SYNDROME ASSOCIATED WITH THE UNDERLYING PRIMARY DISEASE, AND CHARACTERIZED BY LOSS OF SKELETAL MUSCLE WITH OR WITHOUT LOSS OF FAT TISSUE. PATIENTS WITH CACHEXIA FACE DIRE SYMPTOMS LIKE DYSPNEA, FATIGUE, EDEMA, EXERCISE INTOLERANCE, AND LOW RESPONSIVENESS TO MEDICAL THERAPY, WHICH WORSEN QUALITY OF LIFE. BECAUSE CACHEXIA IS NOT A STAND-ALONE DISORDER, TREATING PRIMARY DISEASE - SUCH AS CANCER - TAKES PRECEDENCE FOR THE PHYSICIAN, AND IT REMAINS MOSTLY A NEGLECTED ILLNESS. EXISTING CLINICAL TRIALS HAVE DEMONSTRATED LIMITED SUCCESS MOSTLY BECAUSE OF THEIR MONOTHERAPEUTIC APPROACH AND LATE DETECTION OF THE SYNDROME. TO CONQUER CACHEXIA, IT IS ESSENTIAL TO IDENTIFY AS MANY MOLECULAR TARGETS AS POSSIBLE USING THE LATEST TECHNOLOGIES WE HAVE AT OUR DISPOSAL. IN THIS REVIEW, WE HAVE DISCUSSED DIFFERENT ASPECTS OF CACHEXIA, WHICH INCLUDE VARIOUS DISEASE SETTINGS, ACTIVE MOLECULAR PATHWAYS, AND RECENT NOVEL ADVANCES MADE IN THIS FIELD TO UNDERSTAND CONSEQUENCES OF THIS ILLNESS. WE ALSO DISCUSS ROLES OF THE SIRTUINS, THE NAD(+)-DEPENDENT LYSINE DEACETYLASES, MICRORNAS, CERTAIN DIETARY OPTIONS, AND EPIGENETIC DRUGS AS POTENTIAL APPROACHES, WHICH CAN BE USED TO TACKLE CACHEXIA AS EARLY AS POSSIBLE IN ITS COURSE. 2019 2 292 35 AGING AND SUSCEPTIBILITY TO PULMONARY DISEASE. THE LUNGS ARE CONTINUALLY SUBJECTED TO NOXIOUS AND INERT SUBSTANCES, ARE IMMUNOLOGICALLY ACTIVE, AND ARE IN A CONSTANT STATE OF DAMAGE AND REPAIR. THIS MAKES THE PULMONARY SYSTEM PARTICULARLY VULNERABLE TO DISEASES OF AGING. AGING CAN BE UNDERSTOOD AS RANDOM MOLECULAR DAMAGE THAT IS UNREPAIRED AND ACCUMULATES OVER TIME, RESULTING IN CELLULAR DEFECTS AND TISSUE DYSFUNCTION. THE BREAKDOWN OF CELLULAR MECHANISMS, INCLUDING STEM CELL EXHAUSTION, GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATION, LOSS OF PROTEOSTASIS, DEREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, ALTERED INTERCELLULAR COMMUNICATION, AND CHANGES IN THE EXTRACELLULAR MATRIX IS THOUGHT TO ADVANCE THE AGING PROCESS ITSELF. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), IDIOPATHIC PULMONARY FIBROSIS (IPF), AND CANCERS ILLUSTRATE A PATHOLOGIC BREAKDOWN IN THESE MECHANISMS BEYOND NORMAL AGING. THE IMMUNE SYSTEM BECOMES LESS EFFECTIVE WITH ADVANCING AGE. THERE IS A LOW-LEVEL STATE OF CHRONIC INFLAMMATION TERMED INFLAMMAGING WHICH IS THOUGHT TO BE DRIVEN BY IMMUNOSENESCENCE, THE CHANGES IN THE INNATE AND ADAPTIVE IMMUNE SYSTEMS WITH ADVANCING AGE THAT LEAD TO DYSREGULATION AND DECREASED EFFECTIVENESS OF THE IMMUNE SYSTEM. THESE PROCESSES OF AGING LEAD TO EXPECTED CHANGES IN THE FORM AND FUNCTION OF THE RESPIRATORY SYSTEM, MOST NOTABLY A LOSS OF LUNG ELASTICITY, DECREASE IN RESPIRATORY MUSCLE STRENGTH, INCREASE IN VENTILATION-PERFUSION MISMATCHING, AND STIFFENING OF THE VASCULATURE. THE ASTUTE CLINICIAN IS AWARE OF THESE EXPECTED FINDINGS AND DOES NOT OFTEN ATTRIBUTE DYSPNEA TO AGING ALONE. MAINTAINING A LOW THRESHOLD TO INVESTIGATE FOR COMORBID DISEASE AND UNDERSTANDING HOW PULMONARY DISEASE PRESENTS DIFFERENTLY IN THE ELDERLY THAN IN YOUNGER ADULTS CAN IMPROVE CLINICAL OUTCOMES. (C) 2022 AMERICAN PHYSIOLOGICAL SOCIETY. COMPR PHYSIOL 12:3509-3522, 2022. 2022 3 255 31 ADVANCES IN MYELOFIBROSIS: A CLINICAL CASE APPROACH. PRIMARY MYELOFIBROSIS IS A MEMBER OF THE MYELOPROLIFERATIVE NEOPLASMS, A DIVERSE GROUP OF BONE MARROW MALIGNANCIES. SYMPTOMS OF MYELOFIBROSIS, PARTICULARLY THOSE ASSOCIATED WITH SPLENOMEGALY (ABDOMINAL DISTENTION AND PAIN, EARLY SATIETY, DYSPNEA, AND DIARRHEA) AND CONSTITUTIONAL SYMPTOMS, REPRESENT A SUBSTANTIAL BURDEN TO PATIENTS. MOST PATIENTS EVENTUALLY DIE FROM THE DISEASE, WITH A MEDIAN SURVIVAL RANGING FROM APPROXIMATELY 5-7 YEARS. MUTATIONS IN JANUS KINASE 2 (JAK2), A KINASE THAT IS ESSENTIAL FOR THE NORMAL DEVELOPMENT OF ERYTHROCYTES, GRANULOCYTES, AND PLATELETS, NOTABLY THE V617F MUTATION, HAVE BEEN IDENTIFIED IN APPROXIMATELY 50% OF PATIENTS WITH MYELOFIBROSIS. THE APPROVAL OF A JAK2 INHIBITOR IN 2011 HAS IMPROVED THE OUTLOOK OF MANY PATIENTS WITH MYELOFIBROSIS AND HAS CHANGED THE TREATMENT LANDSCAPE. THIS ARTICLE FOCUSES ON SOME OF THE IMPORTANT ISSUES IN CURRENT MYELOFIBROSIS TREATMENT MANAGEMENT, INCLUDING DIFFERENTIATION OF MYELOFIBROSIS FROM ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA, UP-DATED DATA ON THE RESULTS OF JAK2 INHIBITOR THERAPY, THE ROLE OF EPIGENETIC MECHANISMS IN MYELOFIBROSIS PATHOGENESIS, INVESTIGATIONAL THERAPIES FOR MYELOFIBROSIS, AND ADVANCES IN HEMATOPOIETIC STEM CELL TRANSPLANT. THREE MYELOFIBROSIS CASES ARE INCLUDED TO UNDERSCORE THE ISSUES IN DIAGNOSING AND TREATING THIS COMPLEX DISEASE. 2013 4 3802 38 INTERSTITIAL LUNG DISEASE IN CONNECTIVE TISSUE DISEASE: A COMMON LESION WITH HETEROGENEOUS MECHANISMS AND TREATMENT CONSIDERATIONS. CONNECTIVE TISSUE DISEASE (CTD) RELATED INTERSTITIAL LUNG DISEASE (CTD-ILD) IS ONE OF THE LEADING CAUSES OF MORBIDITY AND MORTALITY OF CTD. CLINICALLY, CTD-ILD IS HIGHLY HETEROGENOUS AND INVOLVES RHEUMATIC IMMUNITY AND MULTIPLE MANIFESTATIONS OF RESPIRATORY COMPLICATIONS AFFECTING THE AIRWAYS, VESSELS, LUNG PARENCHYMA, PLEURA, AND RESPIRATORY MUSCLES. THE MAJOR PATHOLOGICAL FEATURES OF CTD ARE CHRONIC INFLAMMATION OF BLOOD VESSELS AND CONNECTIVE TISSUES, WHICH CAN AFFECT ANY ORGAN LEADING TO MULTI-SYSTEM DAMAGE. THE HUMAN LUNG IS PARTICULARLY VULNERABLE TO SUCH DAMAGE BECAUSE ANATOMICALLY IT IS ABUNDANT WITH COLLAGEN AND BLOOD VESSELS. THE COMPLEX ETIOLOGY OF CTD-ILD INCLUDES GENETIC RISKS, EPIGENETIC CHANGES, AND DYSREGULATED IMMUNITY, WHICH INTERACT LEADING TO DISEASE UNDER VARIOUS ILL-DEFINED ENVIRONMENTAL TRIGGERS. CTD-ILD EXHIBITS A BROAD SPECTRA OF CLINICAL MANIFESTATIONS: FROM ASYMPTOMATIC TO SEVERE DYSPNEA; FROM SINGLE-ORGAN RESPIRATORY SYSTEM INVOLVEMENT TO MULTI-ORGAN INVOLVEMENT. THE DISEASE COURSE IS ALSO FEATURED BY REMISSIONS AND RELAPSES. IT CAN RANGE FROM STABILITY OR SLOW PROGRESSION OVER SEVERAL YEARS TO RAPID DETERIORATION. IT CAN ALSO PRESENT CLINICALLY AS HIGHLY PROGRESSIVE FROM THE INITIAL ONSET OF DISEASE. CURRENTLY, THE DIAGNOSIS OF CTD-ILD IS PRIMARILY BASED ON DISTINCT PATHOLOGY SUBTYPE(S), IMAGING, AS WELL AS RELATED CTD AND AUTOANTIBODIES PROFILES. METICULOUS COMPREHENSIVE CLINICAL AND LABORATORY ASSESSMENT TO IMPROVE THE DIAGNOSTIC PROCESS AND MANAGEMENT STRATEGIES ARE MUCH NEEDED. IN THIS REVIEW, WE FOCUS ON EXAMINING THE PATHOGENESIS OF CTD-ILD WITH RESPECT TO GENETICS, ENVIRONMENTAL FACTORS, AND IMMUNOLOGICAL FACTORS. WE ALSO DISCUSS THE CURRENT STATE OF KNOWLEDGE AND ELABORATE ON THE CLINICAL CHARACTERISTICS OF CTD-ILD, DISTINCT PATHOHISTOLOGICAL SUBTYPES, IMAGING FEATURES, AND RELATED AUTOANTIBODIES. FURTHERMORE, WE COMMENT ON THE IDENTIFICATION OF HIGH-RISK PATIENTS AND ADDRESS HOW TO STRATIFY PATIENTS FOR PRECISION MEDICINE MANAGEMENT APPROACHES. 2021 5 5025 36 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 6 3513 41 IDIOPATHIC PULMONARY FIBROSIS: PATHOGENESIS AND MANAGEMENT. BACKGROUND: IDIOPATHIC PULMONARY FIBROSIS (IPF) IS A CHRONIC, PROGRESSIVE DISEASE CHARACTERIZED BY THE ABERRANT ACCUMULATION OF FIBROTIC TISSUE IN THE LUNGS PARENCHYMA, ASSOCIATED WITH SIGNIFICANT MORBIDITY AND POOR PROGNOSIS. THIS REVIEW WILL PRESENT THE SUBSTANTIAL ADVANCES ACHIEVED IN THE UNDERSTANDING OF IPF PATHOGENESIS AND IN THE THERAPEUTIC OPTIONS THAT CAN BE OFFERED TO PATIENTS, AND WILL ADDRESS THE ISSUES REGARDING DIAGNOSIS AND MANAGEMENT THAT ARE STILL OPEN. MAIN BODY: OVER THE LAST TWO DECADES MUCH HAS BEEN CLARIFIED ABOUT THE PATHOGENIC PATHWAYS UNDERLYING THE DEVELOPMENT AND PROGRESSION OF THE LUNG SCARRING IN IPF. SUSTAINED ALVEOLAR EPITHELIAL MICRO-INJURY AND ACTIVATION HAS BEEN RECOGNISED AS THE TRIGGER OF SEVERAL BIOLOGICAL EVENTS OF DISORDERED REPAIR OCCURRING IN GENETICALLY SUSCEPTIBLE AGEING INDIVIDUALS. DESPITE MULTIDISCIPLINARY TEAM DISCUSSION HAS DEMONSTRATED TO INCREASE DIAGNOSTIC ACCURACY, PATIENTS CAN STILL REMAIN UNCLASSIFIED WHEN THE CURRENT DIAGNOSTIC CRITERIA ARE STRICTLY APPLIED, REQUIRING THE IDENTIFICATION OF A USUAL INTERSTITIAL PATTERN EITHER ON HIGH-RESOLUTION COMPUTED TOMOGRAPHY SCAN OR LUNG BIOPSY. OUTSTANDING ACHIEVEMENTS HAVE BEEN MADE IN THE MANAGEMENT OF THESE PATIENTS, AS NINTEDANIB AND PIRFENIDONE CONSISTENTLY PROVED TO REDUCE THE RATE OF PROGRESSION OF THE FIBROTIC PROCESS. HOWEVER, MANY UNCERTAINTIES STILL LIE IN THE CORRECT USE OF THESE DRUGS, RANGING FROM THE INITIAL CHOICE OF THE DRUG, THE APPROPRIATE TIMING FOR TREATMENT AND THE BENEFIT-RISK RATIO OF A COMBINED TREATMENT REGIMEN. SEVERAL NOVEL COMPOUNDS ARE BEING DEVELOPED IN THE PERSPECTIVE OF A MORE TARGETED THERAPEUTIC APPROACH; IN THE MEANTIME, THE SUPPORTIVE CARE OF THESE PATIENTS AND THEIR CARERS SHOULD BE APPROPRIATELY PRIORITIZED, AND GREATER EFFORTS SHOULD BE MADE TOWARD THE PROMPT IDENTIFICATION AND MANAGEMENT OF RELEVANT COMORBIDITIES. CONCLUSIONS: BUILDING ON THE ADVANCES IN THE UNDERSTANDING OF IPF PATHOBIOLOGY, THE FURTHER INVESTIGATION OF THE ROLE OF GENE VARIANTS, EPIGENETIC ALTERATIONS AND OTHER MOLECULAR BIOMARKERS REFLECTING DISEASE ACTIVITY AND BEHAVIOUR WILL HOPEFULLY ENABLE EARLIER AND MORE CONFIDENT DIAGNOSIS, IMPROVE DISEASE PHENOTYPING AND SUPPORT THE DEVELOPMENT OF NOVEL AGENTS FOR PERSONALIZED TREATMENT OF IPF. 2018 7 4663 38 NEW HORIZONS: NOVEL APPROACHES TO ENHANCE HEALTHSPAN THROUGH TARGETING CELLULAR SENESCENCE AND RELATED AGING MECHANISMS. THE ELDERLY POPULATION IS INCREASING FASTER THAN OTHER SEGMENTS OF THE POPULATION THROUGHOUT THE WORLD. AGE IS THE LEADING PREDICTOR FOR MOST CHRONIC DISEASES AND DISORDERS, MULTIMORBIDITY, GERIATRIC SYNDROMES, AND IMPAIRED ABILITY TO RECOVER FROM ACCIDENTS OR ILLNESSES. ENHANCING THE DURATION OF HEALTH AND INDEPENDENCE, TERMED HEALTHSPAN, WOULD BE MORE DESIRABLE THAN EXTENDING LIFESPAN MERELY BY PROLONGING THE PERIOD OF MORBIDITY TOWARD THE END OF LIFE. THE GEROSCIENCE HYPOTHESIS POSITS THAT HEALTHSPAN CAN BE EXTENDED BY TARGETING FUNDAMENTAL AGING MECHANISMS, RATHER THAN ATTEMPTING TO ADDRESS EACH AGE-RELATED DISEASE ONE AT A TIME, ONLY SO THE AFFLICTED INDIVIDUAL SURVIVES DISABLED AND DIES SHORTLY AFTERWARD OF ANOTHER AGE-RELATED DISEASE. THESE FUNDAMENTAL AGING MECHANISMS INCLUDE, AMONG OTHERS, CHRONIC INFLAMMATION, FIBROSIS, STEM CELL/ PROGENITOR DYSFUNCTION, DNA DAMAGE, EPIGENETIC CHANGES, METABOLIC SHIFTS, DESTRUCTIVE METABOLITE GENERATION, MITOCHONDRIAL DYSFUNCTION, MISFOLDED OR AGGREGATED PROTEIN ACCUMULATION, AND CELLULAR SENESCENCE. THESE PROCESSES APPEAR TO BE TIGHTLY INTERLINKED, AS TARGETING ANY ONE APPEARS TO AFFECT MANY OF THE REST, UNDERLYING OUR UNITARY THEORY OF FUNDAMENTAL AGING MECHANISMS. INTERVENTIONS TARGETING MANY FUNDAMENTAL AGING PROCESSES ARE BEING DEVELOPED, INCLUDING DIETARY MANIPULATIONS, METFORMIN, MTOR (MECHANISTIC TARGET OF RAPAMYCIN) INHIBITORS, AND SENOLYTICS, WHICH ARE IN EARLY HUMAN TRIALS. THESE INTERVENTIONS COULD LEAD TO GREATER HEALTHSPAN BENEFITS THAN TREATING AGE-RELATED DISEASES ONE AT A TIME. TO ILLUSTRATE THESE POINTS, WE FOCUS ON CELLULAR SENESCENCE AND THERAPIES IN DEVELOPMENT TO TARGET SENESCENT CELLS. COMBINING INTERVENTIONS TARGETING AGING MECHANISMS WITH DISEASE-SPECIFIC DRUGS COULD RESULT IN MORE THAN ADDITIVE BENEFITS FOR CURRENTLY DIFFICULT-TO-TREAT OR INTRACTABLE DISEASES. MORE RESEARCH ATTENTION NEEDS TO BE DEVOTED TO TARGETING FUNDAMENTAL AGING PROCESSES. 2021 8 182 27 ACCELERATED LUNG AGING AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE PREVALENCE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INCREASES EXPONENTIALLY WITH AGING. ITS PATHOGENESIS, HOWEVER, IS NOT WELL KNOWN AND ASIDE FROM SMOKING CESSATION, THERE ARE NO DISEASE-MODIFYING TREATMENTS FOR THIS DISEASE. AREAS COVERED: COPD IS ASSOCIATED WITH ACCELERATING AGING AND AGING-RELATED DISEASES. IN THIS REVIEW, WE WILL DISCUSS THE HALLMARKS OF AGING INCLUDING GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATION, LOSS OF PROTEOSTASIS, MITOCHONDRIAL DYSFUNCTION, DEREGULATED NUTRIENT SENSING, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION, WHICH MAY BE INVOLVED IN COPD PATHOGENESIS. EXPERT COMMENTARY: COPD AND THE AGING PROCESS SHARE SIMILAR MOLECULAR AND CELLULAR CHANGES. AGING-RELATED MOLECULAR PATHWAYS MAY REPRESENT NOVEL THERAPEUTIC TARGETS AND BIOMARKERS FOR COPD. 2019 9 5919 30 TARGETING CELLULAR SENESCENCE FOR AGE-RELATED DISEASES: PATH TO CLINICAL TRANSLATION. BEYOND THE PALLIATIVE REACH OF TODAY'S MEDICINES, MEDICAL THERAPIES OF TOMORROW AIM TO TREAT THE ROOT CAUSE OF AGE-RELATED DISEASES BY TARGETING FUNDAMENTAL AGING MECHANISMS. PILLARS OF AGING INCLUDE, AMONG OTHERS, GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION. THE UNITARY THEORY OF FUNDAMENTAL AGING PROCESSES POSITS THAT BY TARGETING ONE FUNDAMENTAL AGING PROCESS, IT MAY BE FEASIBLE TO IMPACT SEVERAL OR ALL OTHERS GIVEN ITS INTERDEPENDENCE. INDEED, PATHOLOGIC ACCUMULATION OF SENESCENT CELLS IS IMPLICATED IN CHRONIC DISEASES AND AGE-ASSOCIATED MORBIDITIES, SUGGESTING THAT SENESCENT CELLS ARE A GOOD TARGET FOR WHOLE-BODY AGING INTERVENTION. PRECLINICAL STUDIES USING SENOLYTICS, AGENTS THAT SELECTIVELY ELIMINATE SENESCENT CELLS, AND SENOMORPHICS, AGENTS THAT INHIBIT PRODUCTION OR RELEASE OF SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE FACTORS, SHOW PROMISE IN SEVERAL AGING AND DISEASE PRECLINICAL MODELS. EARLY CLINICAL TRIALS USING A SENOLYTIC COMBINATION (DASATINIB AND QUERCETIN), AND OTHER SENOLYTICS INCLUDING FLAVONOID, FISETIN, AND BCL-XL INHIBITORS, ILLUSTRATE THE POTENTIAL OF SENOLYTICS TO ALLEVIATE AGE-RELATED DYSFUNCTION AND DISEASES INCLUDING WOUND HEALING. TRANSLATION INTO CLINICAL APPLICATIONS REQUIRES PARALLEL CLINICAL TRIALS ACROSS INSTITUTIONS TO VALIDATE SENOTHERAPEUTICS AS A VANGUARD FOR DELAYING, PREVENTING, OR TREATING AGE-RELATED DISORDERS AND AESTHETIC AGING. 2022 10 2731 28 EXPLORING THE COMPLEX RELATIONSHIP BETWEEN MICROBIOTA AND SYSTEMIC LUPUS ERYTHEMATOSUS. PURPOSE OF REVIEW: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY VARIOUS AUTOANTIBODIES AND MULTI-ORGAN. MICROBIOTA DYSBIOSIS IN THE GUT, SKIN, ORAL, AND OTHER SURFACES HAS A SIGNIFICANT IMPACT ON SLE DEVELOPMENT. THIS ARTICLE SUMMARIZES RELEVANT RESEARCH AND PROVIDES NEW MICROBIOME-RELATED STRATEGIES FOR EXPLORING THE MECHANISMS AND TREATING PATIENTS WITH SLE. RECENT FINDINGS: SLE PATIENTS HAVE DISRUPTIONS IN MULTIPLE MICROBIOMES, WITH THE GUT MICROBIOTA (BACTERIA, VIRUSES, AND FUNGI) AND THEIR METABOLITES BEING THE MOST THOROUGHLY RESEARCHED. THIS DYSBIOSIS CAN PROMOTE SLE PROGRESSION THROUGH MECHANISMS SUCH AS THE LEAKY GUT, MOLECULAR MIMICRY, AND EPIGENETIC REGULATION. NOTWITHSTANDING STUDY CONSTRAINTS ON THE RELATIONSHIP BETWEEN MICROBIOTA AND SLE, SPECIFIC INTERVENTIONS TARGETING THE GUT MICROBIOTA, SUCH AS PROBIOTICS, DIETARY MANAGEMENT, AND FECAL MICROBIOTA TRANSPLANTATION, HAVE EMERGED AS PROMISING SLE THERAPEUTICS. 2023 11 5672 43 SHARED AND DIVERGENT EPIGENETIC MECHANISMS IN CACHEXIA AND SARCOPENIA. SIGNIFICANT LOSS OF MUSCLE MASS MAY OCCUR IN CACHEXIA AND SARCOPENIA, WHICH ARE MAJOR CAUSES OF MORTALITY AND DISABILITY. CACHEXIA REPRESENTS A COMPLEX MULTI-ORGAN SYNDROME ASSOCIATED WITH CANCER AND CHRONIC DISEASES. IT IS OFTEN CHARACTERIZED BY BODY WEIGHT LOSS, INFLAMMATION, AND MUSCLE AND ADIPOSE WASTING. PROGRESSIVE MUSCLE LOSS IS ALSO A HALLMARK OF HEALTHY AGING, WHICH IS EMERGING WORLDWIDE AS A MAIN DEMOGRAPHIC TREND. A GREAT CHALLENGE FOR THE HEALTH CARE SYSTEMS IS THE AGE-RELATED DECLINE IN FUNCTIONALITY WHICH THREATENS THE INDEPENDENCE AND QUALITY OF LIFE OF ELDERLY PEOPLE. THIS BIOLOGICAL DECLINE CAN ALSO BE ASSOCIATED WITH FUNCTIONAL MUSCLE LOSS, KNOWN AS SARCOPENIA. PREVIOUS STUDIES HAVE SHOWN THAT MICRORNAS (MIRNAS) PLAY PIVOTAL ROLES IN THE DEVELOPMENT AND PROGRESSION OF MUSCLE WASTING IN BOTH CACHEXIA AND SARCOPENIA. THESE SMALL NON-CODING RNAS, OFTEN CARRIED IN EXTRACELLULAR VESICLES, INHIBIT TRANSLATION BY TARGETING MESSENGER RNAS, THEREFORE REPRESENTING POTENT EPIGENETIC MODULATORS. THE MOLECULAR MECHANISMS BEHIND CACHEXIA AND SARCOPENIA, INCLUDING THE EXPRESSION OF SPECIFIC MIRNAS, SHARE COMMON AND DISTINCTIVE TRENDS. THE AIM OF THE PRESENT REVIEW IS TO COMPILE RECENT EVIDENCE ABOUT SHARED AND DIVERGENT EPIGENETIC MECHANISMS, PARTICULARLY FOCUSING ON MIRNAS, BETWEEN CACHEXIA AND SARCOPENIA TO UNDERSTAND A FACET IN THE UNDERLYING MUSCLE WASTING ASSOCIATED WITH THESE MORBIDITIES AND DISCLOSE POTENTIAL THERAPEUTIC INTERVENTIONS. 2022 12 5799 25 STEPPING OUT OF ANTIQUITY: AN UPDATE ON EMERGING DRUGS FOR THE TREATMENT OF POLYCYTHEMIA VERA. INTRODUCTION: POLYCYTHEMIA VERA IS A CHRONIC HEMATOLOGIC MALIGNANCY FREQUENTLY PRESENTED WITH CONSTITUTIONAL SYMPTOMS AND ASSOCIATED WITH AN INCREASED RISK OF THROMBOSIS, HEMORRHAGE, AND PROGRESSION TO MYELOFIBROSIS OR ACUTE MYELOID LEUKEMIA. CURRENT TREATMENT STRATEGIES REDUCE THROMBOHEMORRHAGIC RISK BY CONTROLLING BLOOD COUNTS AND INHIBITING PLATELETS, BUT OFTEN FAIL TO ADDRESS DISEASE-RELATED SYMPTOMS OR BIOLOGICALLY MODIFY THE DISEASE.AREAS COVERED: WE REVIEW THE CURRENT PARADIGM FOR TREATING POLYCYTHEMIA VERA, HIGHLIGHT AREAS OF UNMET NEED, REVIEW THERAPEUTIC AGENTS IN LATE STAGE CLINICAL DEVELOPMENT, AND PROVIDE AN OVERARCHING VIEW OF HOW THESE EMERGING AGENT MAY FIT INTO THE FUTURE ARMAMENTARIUM OF POLYCYTHEMIA VERA TREATMENTS.EXPERT OPINION: THE SHIFT FROM FOCUSING SOLELY ON SECONDARY PREVENTION OF THROMBOHEMORRHAGIC EVENTS TO A COMPREHENSIVE TREATMENT STRATEGY THAT ADDITIONALLY AIMS TO IMPROVE QUALITY OF LIFE AND PREVENT DISEASE PROGRESSION HAS RESULTED IN A RAPIDLY EVOLVING THERAPEUTIC LANDSCAPE THAT PROMISES TO MOVE THE TREATMENT OF POLYCYTHEMIA VERA OUT OF ANTIQUITY INTO THE MODERN AGE. 2021 13 5161 40 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 14 5257 37 PROGRESSION OF MYELOPROLIFERATIVE NEOPLASMS (MPN): DIAGNOSTIC AND THERAPEUTIC PERSPECTIVES. CLASSICAL BCR-ABL-NEGATIVE MYELOPROLIFERATIVE NEOPLASMS (MPN) ARE A HETEROGENEOUS GROUP OF HEMATOLOGIC MALIGNANCIES, INCLUDING ESSENTIAL THROMBOCYTHEMIA (ET), POLYCYTHEMIA VERA (PV), AND PRIMARY MYELOFIBROSIS (PMF), AS WELL AS POST-PV-MF AND POST-ET-MF. PROGRESSION TO MORE SYMPTOMATIC DISEASE, SUCH AS OVERT MF OR ACUTE LEUKEMIA, REPRESENTS ONE OF THE MAJOR CAUSES OF MORBIDITY AND MORTALITY. THERE ARE CLINICALLY EVIDENT BUT ALSO SUBCLINICAL TYPES OF MPN PROGRESSION. CLINICALLY EVIDENT PROGRESSION INCLUDES EVOLUTION FROM ET TO PV, ET TO POST-ET-MF, PV TO POST-PV-MF, OR PRE-PMF TO OVERT PMF, AND TRANSFORMATION OF ANY OF THESE SUBTYPES TO MYELODYSPLASTIC NEOPLASMS OR ACUTE LEUKEMIA. THROMBOSIS, MAJOR HEMORRHAGE, SEVERE INFECTIONS, OR INCREASING SYMPTOM BURDEN (E.G., PRURITUS, NIGHT SWEATS) MAY HERALD PROGRESSION. SUBCLINICAL TYPES OF PROGRESSION MAY INCLUDE INCREASES IN THE EXTENT OF BONE MARROW FIBROSIS, INCREASES OF DRIVER GENE MUTATIONAL ALLELE BURDEN, AND CLONAL EVOLUTION. THE UNDERLYING CAUSES OF MPN PROGRESSION ARE DIVERSE AND CAN BE ATTRIBUTED TO GENETIC ALTERATIONS AND CHRONIC INFLAMMATION. PARTICULARLY, BYSTANDER MUTATIONS IN GENES ENCODING EPIGENETIC REGULATORS OR SPLICING FACTORS WERE ASSOCIATED WITH PROGRESSION. FINALLY, COMORBIDITIES SUCH AS SYSTEMIC INFLAMMATION, CARDIOVASCULAR DISEASES, AND ORGAN FIBROSIS MAY AUGMENT THE RISK OF PROGRESSION. THE AIM OF THIS REVIEW WAS TO DISCUSS TYPES AND MECHANISMS OF MPN PROGRESSION AND HOW THEIR KNOWLEDGE MIGHT IMPROVE RISK STRATIFICATION AND THERAPEUTIC INTERVENTION. IN VIEW OF THESE ASPECTS, WE DISCUSS THE POTENTIAL BENEFITS OF EARLY DIAGNOSIS USING MOLECULAR AND FUNCTIONAL IMAGING AND EXPLOITABLE THERAPEUTIC STRATEGIES THAT MAY PREVENT PROGRESSION, BUT ALSO HIGHLIGHT CURRENT CHALLENGES AND METHODOLOGICAL PITFALLS. 2021 15 6442 29 THERAPEUTIC APPROACHES IN MYELOFIBROSIS AND MYELODYSPLASTIC/MYELOPROLIFERATIVE OVERLAP SYNDROMES. THE DISCOVERY OF JAK2 (V617F) A DECADE AGO LED TO OPTIMISM FOR A RAPIDLY DEVELOPING TREATMENT REVOLUTION IN PH(-) MYELOPROLIFERATIVE NEOPLASMS. UNLIKE BCR-ABL, HOWEVER, JAK2 WAS FOUND TO HAVE A MORE HETEROGENEOUS ROLE IN CARCINOGENESIS. THEREFORE, FOR YEARS, DEVELOPMENT OF NEW THERAPIES WAS SLOW, DESPITE STANDARD TREATMENT OPTIONS THAT DID NOT ADDRESS THE OVERWHELMING SYMPTOM BURDEN IN PATIENTS WITH PRIMARY MYELOFIBROSIS (MF), POST-ESSENTIAL THROMBOCYTHEMIA MF, POST-POLYCYTHEMIA VERA MF, AND MYELODYSPLASTIC SYNDROME (MDS)/MYELOPROLIFERATIVE NEOPLASM (MPN) SYNDROMES. JAK-STAT INHIBITORS HAVE CHANGED THIS, DRASTICALLY AMELIORATING SYMPTOMS AND ULTIMATELY BEGINNING TO SHOW EVIDENCE OF IMPACT ON SURVIVAL. NOW, THE GENETIC FOUNDATIONS OF MYELOFIBROSIS AND MDS/MPN ARE RAPIDLY BEING ELUCIDATED AND CONTRIBUTING TO TARGETED THERAPY DEVELOPMENT. THIS HAS BEEN EMPOWERED THROUGH UPDATED RESPONSE CRITERIA FOR MDS/MPN AND REFINED PROGNOSTIC SCORING SYSTEMS IN THESE DISEASES. THE AIM OF THIS ARTICLE IS TO SUMMARIZE CONCISELY THE CURRENT AND RATIONALLY DESIGNED INVESTIGATIONAL THERAPEUTICS DIRECTED AT JAK-STAT, HEDGEHOG, PI3K-AKT, BONE MARROW FIBROSIS, TELOMERASE, AND ROGUE EPIGENETIC SIGNALING. THE REVOLUTION IN IMMUNOTHERAPY AND NOVEL TREATMENTS AIMED AT PREVIOUSLY UNTARGETED SIGNALING PATHWAYS PROVIDES HOPE FOR CONSIDERABLE ADVANCEMENT IN THERAPY OPTIONS FOR THOSE WITH CHRONIC MYELOID DISEASE. 2016 16 3575 41 IMPACT OF MOLECULAR PROFILING ON THE MANAGEMENT OF PATIENTS WITH MYELOFIBROSIS. MYELOFIBROSIS (MF) IS A CHRONIC MYELOPROLIFERATIVE NEOPLASM (MPN) CHARACTERIZED BY A HIGHLY HETEROGENEOUS CLINICAL COURSE, WHICH CAN BE COMPLICATED BY SEVERE CONSTITUTIONAL SYMPTOMS, MASSIVE SPLENOMEGALY, PROGRESSIVE BONE MARROW FAILURE, CARDIOVASCULAR EVENTS, AND DEVELOPMENT OF ACUTE LEUKEMIA. CONSTITUTIVE SIGNALING THROUGH THE JAK-STAT PATHWAY PLAYS A FUNDAMENTAL ROLE IN ITS PATHOGENESIS, GENERALLY DUE TO ACTIVATING MUTATIONS OF JAK2, CALR AND MPL GENES (I.E., THE MPN DRIVER MUTATIONS), PRESENT IN MOST MF PATIENTS. NEXT GENERATION SEQUENCING (NGS) PANEL TESTING HAS SHOWN THAT ADDITIONAL SOMATIC MUTATIONS CAN ALREADY BE DETECTED AT THE TIME OF DIAGNOSIS IN MORE THAN HALF OF PATIENTS, AND THAT THEY ACCUMULATE ALONG THE DISEASE COURSE. THESE MUTATIONS, MOSTLY AFFECTING EPIGENETIC MODIFIERS OR SPLICEOSOME COMPONENTS, MAY COOPERATE WITH MPN DRIVERS TO FAVOR CLONAL DOMINANCE OR INFLUENCE THE CLINICAL PHENOTYPE, AND SOME, SUCH AS HIGH MOLECULAR RISK MUTATIONS, CORRELATE WITH A MORE AGGRESSIVE CLINICAL COURSE WITH POOR TREATMENT RESPONSE. THE CURRENT MAIN ROLE OF MOLECULAR PROFILING IN CLINICAL PRACTICE IS PROGNOSTICATION, PRINCIPALLY FOR SELECTING HIGH-RISK PATIENTS WHO MAY BE CANDIDATES FOR TRANSPLANTATION, THE ONLY CURATIVE TREATMENT FOR MF TO DATE. TO THIS END, CONTEMPORARY PROGNOSTIC MODELS INCORPORATING MOLECULAR DATA ARE USEFUL TOOLS TO DISCRIMINATE DIFFERENT RISK CATEGORIES. ASIDE FROM CERTAIN CLINICAL SITUATIONS, DECISIONS REGARDING MEDICAL TREATMENT ARE NOT BASED ON PATIENT MOLECULAR PROFILING, YET THIS APPROACH MAY BECOME MORE RELEVANT IN NOVEL TREATMENT STRATEGIES, SUCH AS THE USE OF VACCINES AGAINST THE MUTANT FORMS OF JAK2 OR CALR, OR DRUGS DIRECTED AGAINST ACTIONABLE MOLECULAR TARGETS. 2022 17 1398 36 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 18 4519 29 MULTI-OMICS IN CROHN'S DISEASE: NEW INSIGHTS FROM INSIDE. CROHN'S DISEASE (CD) IS AN INFLAMMATORY BOWEL DISEASE (IBD) WITH COMPLEX CLINICAL MANIFESTATIONS SUCH AS CHRONIC DIARRHEA, WEIGHT LOSS AND HEMATOCHEZIA. DESPITE THE INCREASING INCIDENCE WORLDWIDE, CURE OF CD REMAINS EXTREMELY DIFFICULT. THE RAPID DEVELOPMENT OF HIGH-THROUGHPUT SEQUENCING TECHNOLOGY WITH INTEGRATED-OMICS ANALYSES IN RECENT YEARS HAS PROVIDED A NEW MEANS FOR EXPLORING THE PATHOGENESIS, MINING THE BIOMARKERS AND DESIGNING TARGETED PERSONALIZED THERAPEUTICS OF CD. HOST GENOMICS AND EPIGENOMICS UNVEIL HEREDITY-RELATED MECHANISMS OF SUSCEPTIBLE INDIVIDUALS, WHILE MICROBIOME AND METABOLOMICS MAP HOST-MICROBE INTERACTIONS IN CD PATIENTS. PROTEOMICS SHOWS GREAT POTENTIAL IN SEARCHING FOR PROMISING BIOMARKERS. NONETHELESS, SINGLE OMICS TECHNOLOGY CANNOT HOLISTICALLY CONNECT THE MECHANISMS WITH HETEROGENEITY OF PATHOLOGICAL BEHAVIOR IN CD. THE RISE OF MULTI-OMICS ANALYSIS INTEGRATES GENETIC/EPIGENETIC PROFILES WITH PROTEIN/MICROBIAL METABOLITE FUNCTIONALITY, PROVIDING NEW HOPE FOR COMPREHENSIVE AND IN-DEPTH EXPLORATION OF CD. HEREIN, WE EMPHASIZED THE DIFFERENT OMICS FEATURES AND APPLICATIONS OF CD AND DISCUSSED THE CURRENT RESEARCH AND LIMITATIONS OF MULTI-OMICS IN CD. THIS REVIEW WILL UPDATE AND DEEPEN OUR UNDERSTANDING OF CD FROM INTEGRATION OF BROAD OMICS SPECTRA AND WILL PROVIDE NEW EVIDENCE FOR TARGETED INDIVIDUALIZED THERAPEUTICS. 2023 19 4589 26 NANOPARTICLES IN THE DIAGNOSIS AND TREATMENT OF VASCULAR AGING AND RELATED DISEASES. AGING-INDUCED ALTERNATIONS OF VASCULATURE STRUCTURES, PHENOTYPES, AND FUNCTIONS ARE KEY IN THE OCCURRENCE AND DEVELOPMENT OF VASCULAR AGING-RELATED DISEASES. MULTIPLE MOLECULAR AND CELLULAR EVENTS, SUCH AS OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VASCULAR INFLAMMATION, CELLULAR SENESCENCE, AND EPIGENETIC ALTERATIONS ARE HIGHLY ASSOCIATED WITH VASCULAR AGING PHYSIOPATHOLOGY. ADVANCES IN NANOPARTICLES AND NANOTECHNOLOGY, WHICH CAN REALIZE SENSITIVE DIAGNOSTIC MODALITIES, EFFICIENT MEDICAL TREATMENT, AND BETTER PROGNOSIS AS WELL AS LESS ADVERSE EFFECTS ON NON-TARGET TISSUES, PROVIDE AN AMAZING WINDOW IN THE FIELD OF VASCULAR AGING AND RELATED DISEASES. THROUGHOUT THIS REVIEW, WE PRESENTED CURRENT KNOWLEDGE ON CLASSIFICATION OF NANOPARTICLES AND THE RELATIONSHIP BETWEEN VASCULAR AGING AND RELATED DISEASES. IMPORTANTLY, WE COMPREHENSIVELY SUMMARIZED THE POTENTIAL OF NANOPARTICLES-BASED DIAGNOSTIC AND THERAPEUTIC TECHNIQUES IN VASCULAR AGING AND RELATED DISEASES, INCLUDING CARDIOVASCULAR DISEASES, CEREBROVASCULAR DISEASES, AS WELL AS CHRONIC KIDNEY DISEASES, AND DISCUSSED THE ADVANTAGES AND LIMITATIONS OF THEIR CLINICAL APPLICATIONS. 2022 20 763 27 CAUSES OF PULMONARY FIBROSIS IN THE ELDERLY. IDIOPATHIC PULMONARY FIBROSIS (IPF) IS THE MOST COMMON AND MOST LETHAL TYPE OF IDIOPATHIC INTERSTITIAL PNEUMONIA. IT IS A CHRONIC, AGING-ASSOCIATED LUNG DISEASE CHARACTERIZED BY FIBROTIC FOCI AND INFLAMMATORY INFILTRATES, WITH NO CURE AND VERY LIMITED THERAPEUTIC OPTIONS. ALTHOUGH ITS ETIOLOGY IS UNKNOWN, SEVERAL PATHOGENIC PATHWAYS HAVE BEEN DESCRIBED THAT COULD EXPLAIN THIS PROCESS, INVOLVING AGING, ENVIRONMENTAL FACTORS, GENOMIC INSTABILITY, LOSS OF PROTEOSTASIS, TELOMERE ATTRITION, EPIGENETIC CHANGES, MITOCHONDRIAL DYSFUNCTION, CELL SENESCENCE, AND ALTERED INTERCELLULAR COMMUNICATION. ONE OF THE MAIN PROGNOSTIC FACTORS FOR THE DEVELOPMENT OF IPF IN BROAD EPIDEMIOLOGICAL STUDIES IS AGE. THE INCIDENCE INCREASES WITH AGE, MAKING THIS A DISEASE THAT PREDOMINANTLY AFFECTS THE ELDERLY POPULATION, BEING EXCEPTIONAL UNDER 45 YEARS OF AGE. HOWEVER, THE DEGREE TO WHICH EACH OF THESE MECHANISMS IS INVOLVED IN THE ETIOLOGY OF THE UNCONTROLLED FIBROGENESIS THAT DEFINES IPF IS STILL UNKNOWN. CLARIFYING THESE QUESTIONS IS CRUCIAL TO THE DEVELOPMENT OF POINTS OF INTERVENTION IN THE PATHOGENESIS OF THE DISEASE. THIS REVIEW BRIEFLY SUMMARIZES WHAT IS KNOWN ABOUT EACH POSSIBLE ETIOLOGICAL FACTOR, AND THE QUESTIONS THAT MOST URGENTLY NEED TO BE ADDRESSED. 2018