1 4191 137 METABOLIC LANDSCAPE IN CARDIAC AGING: INSIGHTS INTO MOLECULAR BIOLOGY AND THERAPEUTIC IMPLICATIONS. CARDIAC AGING IS EVIDENT BY A REDUCTION IN FUNCTION WHICH SUBSEQUENTLY CONTRIBUTES TO HEART FAILURE. THE METABOLIC MICROENVIRONMENT HAS BEEN IDENTIFIED AS A HALLMARK OF MALIGNANCY, BUT RECENT STUDIES HAVE SHED LIGHT ON ITS ROLE IN CARDIOVASCULAR DISEASES (CVDS). VARIOUS METABOLIC PATHWAYS IN CARDIOMYOCYTES AND NONCARDIOMYOCYTES DETERMINE CELLULAR SENESCENCE IN THE AGING HEART. METABOLIC ALTERATION IS A COMMON PROCESS THROUGHOUT CARDIAC DEGENERATION. IMPORTANTLY, THE INVOLVEMENT OF CELLULAR SENESCENCE IN CARDIAC INJURIES, INCLUDING HEART FAILURE AND MYOCARDIAL ISCHEMIA AND INFARCTION, HAS BEEN REPORTED. HOWEVER, METABOLIC COMPLEXITY AMONG HUMAN AGING HEARTS HINDERS THE DEVELOPMENT OF STRATEGIES THAT TARGETS METABOLIC SUSCEPTIBILITY. ADVANCES OVER THE PAST DECADE HAVE LINKED CELLULAR SENESCENCE AND FUNCTION WITH THEIR METABOLIC REPROGRAMMING PATHWAY IN CARDIAC AGING, INCLUDING AUTOPHAGY, OXIDATIVE STRESS, EPIGENETIC MODIFICATIONS, CHRONIC INFLAMMATION, AND MYOCYTE SYSTOLIC PHENOTYPE REGULATION. IN ADDITION, METABOLIC STATUS IS INVOLVED IN CRUCIAL ASPECTS OF MYOCARDIAL BIOLOGY, FROM FIBROSIS TO HYPERTROPHY AND CHRONIC INFLAMMATION. HOWEVER, FURTHER ELUCIDATION OF THE METABOLISM INVOLVEMENT IN CARDIAC DEGENERATION IS STILL NEEDED. THUS, DECIPHERING THE MECHANISMS UNDERLYING HOW METABOLIC REPROGRAMMING IMPACTS CARDIAC AGING IS THOUGHT TO CONTRIBUTE TO THE NOVEL INTERVENTIONS TO PROTECT OR EVEN RESTORE CARDIAC FUNCTION IN AGING HEARTS. HERE, WE SUMMARIZE EMERGING CONCEPTS ABOUT METABOLIC LANDSCAPES OF CARDIAC AGING, WITH SPECIFIC FOCUSES ON WHY METABOLIC PROFILE ALTERS DURING CARDIAC DEGENERATION AND HOW WE COULD UTILIZE THE CURRENT KNOWLEDGE TO IMPROVE THE MANAGEMENT OF CARDIAC AGING. 2023 2 4204 38 METABOLISM, EPIGENETICS, AND CAUSAL INFERENCE IN HEART FAILURE. EUKARYOTES MUST BALANCE THE METABOLIC AND CELL DEATH ACTIONS OF MITOCHONDRIA VIA CONTROL OF GENE EXPRESSION AND CELL FATE BY CHROMATIN, THEREBY FUNCTIONALLY BINDING THE METABOLOME AND EPIGENOME. THIS INTERACTION HAS FAR-REACHING IMPLICATIONS FOR CHRONIC DISEASES IN HUMANS, THE MOST COMMON OF WHICH ARE THOSE OF THE CARDIOVASCULAR SYSTEM. THE MOST DEVASTATING CONSEQUENCE OF CARDIOVASCULAR DISEASE, HEART FAILURE, IS NOT A SINGLE DISEASE, DIAGNOSIS, OR ENDPOINT. HUMAN AND ANIMAL STUDIES HAVE REVEALED THAT, REGARDLESS OF ETIOLOGY AND SYMPTOMS, HEART FAILURE IS UNIVERSALLY ASSOCIATED WITH ABNORMAL METABOLISM AND GENE EXPRESSION - TO FRAME THIS AS CAUSE OR CONSEQUENCE, HOWEVER, MAY BE TO WRONGFOOT THE QUESTION. THIS ESSAY AIMS TO CHALLENGE CURRENT THINKING ON METABOLIC-EPIGENETIC CROSSTALK IN HEART FAILURE, PRESENTING HYPOTHESES FOR HOW CHRONIC DISEASES ARISE, TAKE HOLD, AND PERSIST. WE UNPACK ASSUMPTIONS ABOUT THE ORDER OF OPERATIONS FOR GENE EXPRESSION AND METABOLISM, EXPLORING RECENT FINDINGS IN NONCARDIAC SYSTEMS THAT LINK METABOLIC INTERMEDIATES DIRECTLY TO CHROMATIN REMODELING. LASTLY, WE DISCUSS POTENTIAL MECHANISMS BY WHICH CHROMATIN MAY SERVE AS A SUBSTRATE FOR METABOLIC MEMORY, AND HOW CHANGES IN CELLULAR TRANSCRIPTOMES (AND HENCE IN CELLULAR BEHAVIOR) IN RESPONSE TO STRESS CORRESPOND TO GLOBAL CHANGES IN CHROMATIN ACCESSIBILITY AND STRUCTURE. 2020 3 5572 30 ROLE OF MICRORNA IN DIABETIC CARDIOMYOPATHY: FROM MECHANISM TO INTERVENTION. DIABETIC CARDIOMYOPATHY IS A CHRONIC AND IRREVERSIBLE HEART COMPLICATION IN DIABETIC PATIENTS, AND IS CHARACTERIZED BY COMPLEX PATHOPHYSIOLOGIC EVENTS INCLUDING EARLY DIASTOLIC DYSFUNCTION, CARDIAC HYPERTROPHY, VENTRICULAR DILATION AND SYSTOLIC DYSFUNCTION, EVENTUALLY RESULTING IN HEART FAILURE. DESPITE THESE CHARACTERISTICS, THE UNDERLYING MECHANISMS LEADING TO DIABETIC CARDIOMYOPATHY ARE STILL ELUSIVE. RECENT STUDIES HAVE IMPLICATED MICRORNA, A SMALL AND HIGHLY CONSERVED NON-CODING RNA MOLECULE, IN THE ETIOLOGY OF DIABETES AND ITS COMPLICATIONS, SUGGESTING A POTENTIALLY NOVEL APPROACH FOR THE DIAGNOSIS AND TREATMENT OF DIABETIC CARDIOMYOPATHY. THIS BRIEF REVIEW AIMS AT CAPTURING RECENT STUDIES RELATED TO THE ROLE OF MICRORNA IN DIABETIC CARDIOMYOPATHY. THIS ARTICLE IS PART OF A SPECIAL ISSUE ENTITLED: GENETIC AND EPIGENETIC CONTROL OF HEART FAILURE - EDITED BY JUN REN & MEGAN YINGMEI ZHANG. 2017 4 3181 23 HALLMARKS OF AGING: AN EXPANDING UNIVERSE. AGING IS DRIVEN BY HALLMARKS FULFILLING THE FOLLOWING THREE PREMISES: (1) THEIR AGE-ASSOCIATED MANIFESTATION, (2) THE ACCELERATION OF AGING BY EXPERIMENTALLY ACCENTUATING THEM, AND (3) THE OPPORTUNITY TO DECELERATE, STOP, OR REVERSE AGING BY THERAPEUTIC INTERVENTIONS ON THEM. WE PROPOSE THE FOLLOWING TWELVE HALLMARKS OF AGING: GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DISABLED MACROAUTOPHAGY, DEREGULATED NUTRIENT-SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, ALTERED INTERCELLULAR COMMUNICATION, CHRONIC INFLAMMATION, AND DYSBIOSIS. THESE HALLMARKS ARE INTERCONNECTED AMONG EACH OTHER, AS WELL AS TO THE RECENTLY PROPOSED HALLMARKS OF HEALTH, WHICH INCLUDE ORGANIZATIONAL FEATURES OF SPATIAL COMPARTMENTALIZATION, MAINTENANCE OF HOMEOSTASIS, AND ADEQUATE RESPONSES TO STRESS. 2023 5 6374 42 THE ROLE OF MITOCHONDRIA IN MYOCARDIAL DAMAGE CAUSED BY ENERGY METABOLISM DISORDERS: FROM MECHANISMS TO THERAPEUTICS. MYOCARDIAL DAMAGE IS THE MOST SERIOUS PATHOLOGICAL CONSEQUENCE OF CARDIOVASCULAR DISEASES AND AN IMPORTANT REASON FOR THEIR HIGH MORTALITY. IN RECENT YEARS, BECAUSE OF THE HIGH PREVALENCE OF SYSTEMIC ENERGY METABOLISM DISORDERS (E.G., OBESITY, DIABETES MELLITUS, AND METABOLIC SYNDROME), COMPLICATIONS OF MYOCARDIAL DAMAGE CAUSED BY THESE DISORDERS HAVE ATTRACTED WIDESPREAD ATTENTION. ENERGY METABOLISM DISORDERS ARE INDEPENDENT OF TRADITIONAL INJURY-RELATED RISK FACTORS, SUCH AS ISCHEMIA, HYPOXIA, TRAUMA, AND INFECTION. AN IMBALANCE OF MYOCARDIAL METABOLIC FLEXIBILITY AND MYOCARDIAL ENERGY DEPLETION ARE USUALLY THE INITIAL CHANGES OF MYOCARDIAL INJURY CAUSED BY ENERGY METABOLISM DISORDERS, AND ABNORMAL MORPHOLOGY AND FUNCTIONAL DESTRUCTION OF THE MITOCHONDRIA ARE THEIR IMPORTANT FEATURES. SPECIFICALLY, MITOCHONDRIA ARE THE CENTERS OF ENERGY METABOLISM, AND RECENT EVIDENCE HAS SHOWN THAT DECREASED MITOCHONDRIAL FUNCTION, CAUSED BY AN IMBALANCE IN MITOCHONDRIAL QUALITY CONTROL, MAY PLAY A KEY ROLE IN MYOCARDIAL INJURY CAUSED BY ENERGY METABOLISM DISORDERS. UNDER CHRONIC ENERGY STRESS, MITOCHONDRIA UNDERGO PATHOLOGICAL FISSION, WHILE MITOPHAGY, MITOCHONDRIAL FUSION, AND BIOGENESIS ARE INHIBITED, AND MITOCHONDRIAL PROTEIN BALANCE AND TRANSFER ARE DISTURBED, RESULTING IN THE ACCUMULATION OF NONFUNCTIONAL AND DAMAGED MITOCHONDRIA. CONSEQUENTLY, DAMAGED MITOCHONDRIA LEAD TO MYOCARDIAL ENERGY DEPLETION AND THE ACCUMULATION OF LARGE AMOUNTS OF REACTIVE OXYGEN SPECIES, FURTHER AGGRAVATING THE IMBALANCE IN MITOCHONDRIAL QUALITY CONTROL AND FORMING A VICIOUS CYCLE. IN ADDITION, IMPAIRED MITOCHONDRIA COORDINATE CALCIUM HOMEOSTASIS IMBALANCE, AND EPIGENETIC ALTERATIONS PARTICIPATE IN THE PATHOGENESIS OF MYOCARDIAL DAMAGE. THESE PATHOLOGICAL CHANGES INDUCE RAPID PROGRESSION OF MYOCARDIAL DAMAGE, EVENTUALLY LEADING TO HEART FAILURE OR SUDDEN CARDIAC DEATH. TO INTERVENE MORE SPECIFICALLY IN THE MYOCARDIAL DAMAGE CAUSED BY METABOLIC DISORDERS, WE NEED TO UNDERSTAND THE SPECIFIC ROLE OF MITOCHONDRIA IN THIS CONTEXT IN DETAIL. ACCORDINGLY, PROMISING THERAPEUTIC STRATEGIES HAVE BEEN PROPOSED. WE ALSO SUMMARIZE THE EXISTING THERAPEUTIC STRATEGIES TO PROVIDE A REFERENCE FOR CLINICAL TREATMENT AND DEVELOPING NEW THERAPIES. 2023 6 1175 43 CONTRIBUTIONS OF AGE-RELATED THYMIC INVOLUTION TO IMMUNOSENESCENCE AND INFLAMMAGING. IMMUNE SYSTEM AGING IS CHARACTERIZED BY THE PARADOX OF IMMUNOSENESCENCE (INSUFFICIENCY) AND INFLAMMAGING (OVER-REACTION), WHICH INCORPORATE TWO SIDES OF THE SAME COIN, RESULTING IN IMMUNE DISORDER. IMMUNOSENESCENCE REFERS TO DISRUPTION IN THE STRUCTURAL ARCHITECTURE OF IMMUNE ORGANS AND DYSFUNCTION IN IMMUNE RESPONSES, RESULTING FROM BOTH AGED INNATE AND ADAPTIVE IMMUNITY. INFLAMMAGING, DESCRIBED AS A CHRONIC, STERILE, SYSTEMIC INFLAMMATORY CONDITION ASSOCIATED WITH ADVANCED AGE, IS MAINLY ATTRIBUTED TO SOMATIC CELLULAR SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP) AND AGE-RELATED AUTOIMMUNE PREDISPOSITION. HOWEVER, THE INABILITY TO REDUCE SENESCENT SOMATIC CELLS (SSCS), BECAUSE OF IMMUNOSENESCENCE, EXACERBATES INFLAMMAGING. AGE-RELATED ADAPTIVE IMMUNE SYSTEM DEVIATIONS, PARTICULARLY ALTERED T CELL FUNCTION, ARE DERIVED FROM AGE-RELATED THYMIC ATROPHY OR INVOLUTION, A HALLMARK OF THYMIC AGING. RECENTLY, THERE HAVE BEEN MAJOR DEVELOPMENTS IN UNDERSTANDING HOW AGE-RELATED THYMIC INVOLUTION CONTRIBUTES TO INFLAMMAGING AND IMMUNOSENESCENCE AT THE CELLULAR AND MOLECULAR LEVELS, INCLUDING GENETIC AND EPIGENETIC REGULATION, AS WELL AS DEVELOPMENTS OF MANY POTENTIAL REJUVENATION STRATEGIES. HEREIN, WE DISCUSS THE RESEARCH PROGRESS UNCOVERING HOW AGE-RELATED THYMIC INVOLUTION CONTRIBUTES TO IMMUNOSENESCENCE AND INFLAMMAGING, AS WELL AS THEIR INTERSECTION. WE ALSO DESCRIBE HOW T CELL ADAPTIVE IMMUNITY MEDIATES INFLAMMAGING AND PLAYS A CRUCIAL ROLE IN THE PROGRESSION OF AGE-RELATED NEUROLOGICAL AND CARDIOVASCULAR DISEASES, AS WELL AS CANCER. WE THEN BRIEFLY OUTLINE THE UNDERLYING CELLULAR AND MOLECULAR MECHANISMS OF AGE-RELATED THYMIC INVOLUTION, AND FINALLY SUMMARIZE POTENTIAL REJUVENATION STRATEGIES TO RESTORE AGED THYMIC FUNCTION. 2020 7 4813 34 OBSTRUCTIVE SLEEP APNEA AND HALLMARKS OF AGING. OBSTRUCTIVE SLEEP APNEA (OSA) IS ONE OF THE MOST COMMON SLEEP DISORDERS. SINCE AGING IS A RISK FACTOR FOR OSA DEVELOPMENT, IT IS EXPECTED THAT ITS PREVALENCE WILL INCREASE WITH THE CURRENT INCREASE IN LIFE SPAN. IN RECENT YEARS, SEVERAL STUDIES HAVE SHOWN THAT OSA POTENTIALLY CONTRIBUTES TO FUNCTIONAL DECLINE, MAINLY PROMPTED BY CHRONIC INTERMITTENT HYPOXIA AND SLEEP FRAGMENTATION. HERE, WE PROPOSE THAT OSA MIGHT ANTICIPATE/AGGRAVATE AGING BY INDUCING CELLULAR AND MOLECULAR IMPAIRMENTS THAT CHARACTERIZE THE AGING PROCESS, SUCH AS STEM CELL EXHAUSTION, TELOMERE ATTRITION AND EPIGENETIC CHANGES. WE SUGGEST THAT FURTHER KNOWLEDGE ON THE IMPACT OF OSA ON AGING MECHANISMS MIGHT CONTRIBUTE TO A BETTER UNDERSTANDING OF HOW OSA MIGHT PUTATIVELY ACCELERATE AGING AND AGING-RELATED DISEASES. 2017 8 6357 40 THE ROLE OF HYPERGLYCAEMIA IN THE DEVELOPMENT OF DIABETIC CARDIOMYOPATHY. DIABETES MELLITUS IS A METABOLIC DISORDER WITH A CHRONIC HYPERGLYCAEMIC STATE. CARDIOVASCULAR DISEASES ARE THE PRIMARY CAUSE OF MORTALITY IN PATIENTS WITH DIABETES. INCREASING EVIDENCE SUPPORTS THE EXISTENCE OF DIABETIC CARDIOMYOPATHY, A CARDIAC DYSFUNCTION WITH IMPAIRED CARDIAC CONTRACTION AND RELAXATION, INDEPENDENT OF CORONARY AND/OR VALVULAR COMPLICATIONS. DIABETIC CARDIOMYOPATHY CAN LEAD TO HEART FAILURE. SEVERAL PRECLINICAL AND CLINICAL STUDIES HAVE AIMED TO DECIPHER THE UNDERLYING MECHANISMS OF DIABETIC CARDIOMYOPATHY. AMONG ALL THE CO-FACTORS, HYPERGLYCAEMIA SEEMS TO PLAY AN IMPORTANT ROLE IN THIS PATHOLOGY. HYPERGLYCAEMIA HAS BEEN SHOWN TO ALTER CARDIAC METABOLISM AND FUNCTION THROUGH SEVERAL DELETERIOUS MECHANISMS, SUCH AS OXIDATIVE STRESS, INFLAMMATION, ACCUMULATION OF ADVANCED GLYCATED END-PRODUCTS AND UPREGULATION OF THE HEXOSAMINE BIOSYNTHESIS PATHWAY. THESE MECHANISMS ARE RESPONSIBLE FOR THE ACTIVATION OF HYPERTROPHIC PATHWAYS, EPIGENETIC MODIFICATIONS, MITOCHONDRIAL DYSFUNCTION, CELL APOPTOSIS, FIBROSIS AND CALCIUM MISHANDLING, LEADING TO CARDIAC STIFFNESS, AS WELL AS CONTRACTILE AND RELAXATION DYSFUNCTION. THIS REVIEW AIMS TO DESCRIBE THE HYPERGLYCAEMIC-INDUCED ALTERATIONS THAT PARTICIPATE IN DIABETIC CARDIOMYOPATHY, AND THEIR CORRELATION WITH THE SEVERITY OF THE DISEASE AND PATIENT MORTALITY, AND TO PROVIDE AN OVERVIEW OF CARDIAC OUTCOMES OF GLUCOSE-LOWERING THERAPY. 2021 9 5576 42 ROLE OF MICRORNAS IN THE PATHOGENESIS OF DIABETIC CARDIOMYOPATHY. THE MORBIDITY OF DIABETES MELLITUS HAS BEEN INCREASING ANNUALLY. AS A PROGRESSIVE METABOLIC DISORDER, CHRONIC COMPLICATIONS OCCUR IN THE LATE STAGE OF DIABETES. IN ADDITION, CARDIOVASCULAR DISEASES ACCOUNT FOR THE MAJOR CAUSE OF MORBIDITY AND MORTALITY AMONG THE DIABETIC POPULATION WORLDWIDE. DIABETIC CARDIOMYOPATHY (DCM) IS A TYPE OF DIABETIC HEART DISEASE. PATIENTS WITH DCM SHOW SYMPTOMS AND SIGNS OF HEART FAILURE WHILE NO SPECIFIC CAUSE, SUCH AS CORONARY DISEASE, HYPERTENSION, ALCOHOL CONSUMPTION, OR OTHER STRUCTURAL HEART DISEASES HAS BEEN IDENTIFIED. THE PATHOGENESIS OF DCM IS COMPLEX AND HAS NOT BEEN WELL UNDERSTOOD UNTIL RECENTLY. MICRORNAS (MIRS) BELONG TO A NOVEL FAMILY OF HIGHLY CONSERVED, SHORT, NON-CODING, SINGLE-STRANDED RNA MOLECULES THAT REGULATE TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL GENE EXPRESSION. FURTHERMORE, RECENT STUDIES HAVE DEMONSTRATED AN ASSOCIATION BETWEEN MIRS AND DCM. IN THE CURRENT REVIEW, THE ROLE OF MIRS IN THE PATHOGENESIS OF DCM IS SUMMARIZED. IT WAS CONCLUDED THAT MIRS CONTRIBUTE TO THE REGULATION OF CARDIOMYOCYTE HYPERTROPHY, MYOCARDIAL FIBROSIS, CARDIOMYOCYTE APOPTOSIS, MITOCHONDRIAL DYSFUNCTION, MYOCARDIAL ELECTRICAL REMODELING, EPIGENETIC MODIFICATION AND VARIOUS OTHER PATHOPHYSIOLOGICAL PROCESSES OF DCM. THESE STUDIES MAY PROVIDE NOVEL INSIGHTS INTO TARGETS FOR PREVENTION AND TREATMENT OF THE DISEASE. 2017 10 285 41 AGING AND AGING-RELATED DISEASES: FROM MOLECULAR MECHANISMS TO INTERVENTIONS AND TREATMENTS. AGING IS A GRADUAL AND IRREVERSIBLE PATHOPHYSIOLOGICAL PROCESS. IT PRESENTS WITH DECLINES IN TISSUE AND CELL FUNCTIONS AND SIGNIFICANT INCREASES IN THE RISKS OF VARIOUS AGING-RELATED DISEASES, INCLUDING NEURODEGENERATIVE DISEASES, CARDIOVASCULAR DISEASES, METABOLIC DISEASES, MUSCULOSKELETAL DISEASES, AND IMMUNE SYSTEM DISEASES. ALTHOUGH THE DEVELOPMENT OF MODERN MEDICINE HAS PROMOTED HUMAN HEALTH AND GREATLY EXTENDED LIFE EXPECTANCY, WITH THE AGING OF SOCIETY, A VARIETY OF CHRONIC DISEASES HAVE GRADUALLY BECOME THE MOST IMPORTANT CAUSES OF DISABILITY AND DEATH IN ELDERLY INDIVIDUALS. CURRENT RESEARCH ON AGING FOCUSES ON ELUCIDATING HOW VARIOUS ENDOGENOUS AND EXOGENOUS STRESSES (SUCH AS GENOMIC INSTABILITY, TELOMERE DYSFUNCTION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, COMPROMISE OF AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, ALTERED INTERCELLULAR COMMUNICATION, DEREGULATED NUTRIENT SENSING) PARTICIPATE IN THE REGULATION OF AGING. FURTHERMORE, THOROUGH RESEARCH ON THE PATHOGENESIS OF AGING TO IDENTIFY INTERVENTIONS THAT PROMOTE HEALTH AND LONGEVITY (SUCH AS CALORIC RESTRICTION, MICROBIOTA TRANSPLANTATION, AND NUTRITIONAL INTERVENTION) AND CLINICAL TREATMENT METHODS FOR AGING-RELATED DISEASES (DEPLETION OF SENESCENT CELLS, STEM CELL THERAPY, ANTIOXIDATIVE AND ANTI-INFLAMMATORY TREATMENTS, AND HORMONE REPLACEMENT THERAPY) COULD DECREASE THE INCIDENCE AND DEVELOPMENT OF AGING-RELATED DISEASES AND IN TURN PROMOTE HEALTHY AGING AND LONGEVITY. 2022 11 4379 34 MITOCHONDRIAL DYSFUNCTION AND AGING: INSIGHTS FROM THE ANALYSIS OF EXTRACELLULAR VESICLES. THE PROGRESSIVE DECLINE OF CELL FUNCTION AND INTEGRITY, MANIFESTING CLINICALLY AS INCREASED VULNERABILITY TO ADVERSE OUTCOMES AND DEATH, IS CORE TO BIOLOGICAL AGING. MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ALTERED INTERCELLULAR COMMUNICATION (INCLUDING CHRONIC LOW-GRADE INFLAMMATION), GENOMIC INSTABILITY, TELOMERE ATTRITION, LOSS OF PROTEOSTASIS, ALTERED NUTRIENT SENSING, EPIGENETIC ALTERATIONS, AND STEM CELL EXHAUSTION HAVE BEEN PROPOSED AS HALLMARKS OF AGING. THESE "AGING PILLARS" ARE NOT MUTUALLY EXCLUSIVE, MAKING THE MATTER INTRICATE AND LEAVING NUMEROUS UNANSWERED QUESTIONS. THE CHARACTERIZATION OF CIRCULATING EXTRACELLULAR VESICLES (EVS) HAS RECENTLY ALLOWED SPECIFIC SECRETORY PHENOTYPES ASSOCIATED WITH AGING TO BE IDENTIFIED. AS SUCH, EVS MAY SERVE AS NOVEL BIOMARKERS FOR CAPTURING THE COMPLEXITY OF AGING. BESIDES THE MITOCHONDRIAL(-)LYSOSOMAL AXIS, EV TRAFFICKING HAS BEEN PROPOSED AS AN ADDITIONAL LAYER IN MITOCHONDRIAL QUALITY CONTROL. INDEED, DISRUPTION OF THE MITOCHONDRIAL(-)LYSOSOMAL AXIS COUPLED WITH ABNORMAL EV SECRETION MAY PLAY A ROLE IN THE PATHOGENESIS OF AGING AND SEVERAL DISEASE CONDITIONS. HERE, WE DISCUSS (1) THE MECHANISMS OF EV GENERATION; (2) THE RELATIONSHIP BETWEEN THE MITOCHONDRIAL(-)LYSOSOMAL AXIS AND EV TRAFFICKING IN THE SETTING OF MITOCHONDRIAL QUALITY CONTROL; AND (3) THE PROSPECT OF USING EVS AS AGING BIOMARKERS AND AS DELIVERY SYSTEMS FOR THERAPEUTICS AGAINST AGE-RELATED CONDITIONS. 2019 12 246 45 ADULT STEM CELL THERAPY FOR CARDIAC REPAIR IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION LEADING TO ISCHEMIC HEART FAILURE: AN OVERVIEW OF EVIDENCE FROM THE RECENT CLINICAL TRIALS. BACKGROUND: CARDIOVASCULAR DISEASES (CVD) STILL REPRESENT THE LEADING CAUSE OF MORTALITY WORLDWIDE, DESPITE THE REMARKABLE ADVANCES IN INTERVENTIONAL CARDIOLOGY, CARDIAC SURGERY, AND MODERN PHARMACOTHERAPY, PARTICULARLY IN THE SETTING OF ACUTE MYOCARDIAL INFARCTION (AMI), CHRONIC ISCHEMIC HEART FAILURE (HF), CARDIOMYOPATHY (CM), AND THE ASSOCIATED LEFT VENTRICULAR (LV) DYSFUNCTION. A SIGNIFICANT LOSS OF CARDIOMYOCYTES THAT UNDERLIES ALL OF THESE CONDITIONS WAS PREVIOUSLY CONSIDERED IRREVERSIBLE. HOWEVER, CURRENT EVIDENCE INDICATES THAT THE HUMAN HEART HAS SOME POTENTIAL FOR REPAIR, AND OVER THE PAST DECADE, MANY RESEARCH STUDIES HAVE BEEN EXPLORING THE USE OF STEM CELLS (SCS) TO FACILITATE RESTORATION OF MYOCARDIUM. CONSEQUENTLY, THE SAFETY, FEASIBILITY, AND EFFECTIVENESS OF SC THERAPY HAVE BEEN REPORTED IN MANY RANDOMIZED CLINICAL TRIALS (RCTS), USING DIFFERENT LINEAGES OF ADULT SCS. NEVERTHELESS, THE CLINICAL BENEFITS OF SC THERAPY ARE NOT YET WELL ESTABLISHED. IN THE NEAR FUTURE, UNDERSTANDING OF THE COMPLEX INTERRELATIONS BETWEEN SCS, PARACRINE FACTORS, GENETIC OR EPIGENETIC PREDISPOSITIONS, AND MYOCARDIAL MICROENVIRONMENT, IN THE CONTEXT OF AN INDIVIDUAL PATIENT, WILL BE CRUCIAL FOR TRANSLATION OF THIS KNOWLEDGE INTO PRACTICAL DEVELOPMENT OF SUCCESSFUL, LONG-TERM REGENERATIVE SC THERAPEUTIC APPLICATIONS, IN A GROWING POPULATION OF PATIENTS SUFFERING FROM PREVIOUS MYOCARDIAL INFARCTION (MI) LEADING TO CHRONIC ISCHEMIC CARDIOMYOPATHY. CONCLUSION: THIS OVERVIEW HIGHLIGHTS THE THERAPEUTIC POTENTIAL OF ADULT SCS IN TERMS OF THEIR POSSIBLE REGENERATIVE CAPACITY, SAFETY, AND CLINICAL OUTCOMES, IN PATIENTS WITH AMI, AND/OR SUBSEQUENT HF (DUE TO CHRONIC ISCHEMIC CARDIOMYOPATHY). THIS REVIEW WAS BASED UPON PUBMED DATABASE SEARCH FOR TRIALS ON SC THERAPY, IN PATIENTS WITH AMI AND HF, AND THE MAIN TIMEFRAME WAS SET FROM 2006 TO 2016. 2017 13 465 43 ARE TARGETED THERAPIES FOR DIABETIC CARDIOMYOPATHY ON THE HORIZON? DIABETES INCREASES THE RISK OF HEART FAILURE APPROXIMATELY 2.5-FOLD, INDEPENDENT OF CORONARY ARTERY DISEASE AND OTHER COMORBIDITIES. THIS PROCESS, TERMED DIABETIC CARDIOMYOPATHY, IS CHARACTERIZED BY INITIAL IMPAIRMENT OF LEFT VENTRICULAR (LV) RELAXATION FOLLOWED BY LV CONTRACTILE DYSFUNCTION. POST-MORTEM EXAMINATION REVEALS THAT HUMAN DIASTOLIC DYSFUNCTION IS CLOSELY ASSOCIATED WITH LV DAMAGE, INCLUDING CARDIOMYOCYTE HYPERTROPHY, APOPTOSIS AND FIBROSIS, WITH IMPAIRED CORONARY MICROVASCULAR PERFUSION. THE PATHOPHYSIOLOGICAL MECHANISMS UNDERPINNING THE CHARACTERISTIC FEATURES OF DIABETIC CARDIOMYOPATHY REMAIN POORLY UNDERSTOOD, ALTHOUGH MULTIPLE FACTORS INCLUDING ALTERED LIPID METABOLISM, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM (ER) STRESS, INFLAMMATION, AS WELL AS EPIGENETIC CHANGES, ARE IMPLICATED. DESPITE A RECENT RISE IN RESEARCH INTERROGATING THESE MECHANISMS AND AN INCREASED UNDERSTANDING OF THE CLINICAL IMPORTANCE OF DIABETIC CARDIOMYOPATHY, THERE REMAINS A LACK OF SPECIFIC TREATMENT STRATEGIES. HOW THE CHRONIC METABOLIC DISTURBANCES OBSERVED IN DIABETES LEAD TO STRUCTURAL AND FUNCTIONAL CHANGES REMAINS A PERTINENT QUESTION, AND IT IS HOPED THAT RECENT ADVANCES, PARTICULARLY IN THE AREA OF EPIGENETICS, AMONG OTHERS, MAY PROVIDE SOME ANSWERS. THIS REVIEW HENCE EXPLORES THE TEMPORAL ONSET OF THE PATHOLOGICAL FEATURES OF DIABETIC CARDIOMYOPATHY, AND THEIR RELATIVE CONTRIBUTION TO THE RESULTANT DISEASE PHENOTYPE, AS WELL AS BOTH CURRENT AND POTENTIAL THERAPEUTIC OPTIONS. THE EMERGENCE OF GLUCOSE-OPTIMIZING AGENTS, NAMELY GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS AND SODIUM/GLUCOSE CO-TRANSPORTER (SGLT)2 INHIBITORS THAT CONFER BENEFITS ON CARDIOVASCULAR OUTCOMES, TOGETHER WITH NOVEL EXPERIMENTAL APPROACHES, HIGHLIGHT A NEW AND EXCITING ERA IN DIABETES RESEARCH, WHICH IS LIKELY TO RESULT IN MAJOR CLINICAL IMPACT. 2017 14 5570 36 ROLE OF MELATONIN IN METABOLIC REGULATION. ALTHOUGH THE HUMAN GENOME HAS REMAINED UNCHANGED OVER THE LAST 10,000 YEARS, OUR LIFESTYLE HAS BECOME PROGRESSIVELY MORE DIVERGENT FROM THOSE OF OUR ANCIENT ANCESTORS. THIS MALADAPTIVE CHANGE BECAME APPARENT WITH THE INDUSTRIAL REVOLUTION AND HAS BEEN ACCELERATING IN RECENT DECADES. SOCIALLY, WE ARE PEOPLE OF THE 21ST CENTURY, BUT GENETICALLY WE REMAIN SIMILAR TO OUR EARLY ANCESTORS. IN CONJUNCTION WITH THIS DISCORDANCE BETWEEN OUR ANCIENT, GENETICALLY-DETERMINED BIOLOGY AND THE NUTRITIONAL, CULTURAL AND ACTIVITY PATTERNS IN CONTEMPORARY WESTERN POPULATIONS, MANY DISEASES HAVE EMERGED. ONLY A CENTURY AGO INFECTIOUS DISEASE WAS A MAJOR CAUSE OF MORTALITY, WHEREAS TODAY NON-INFECTIOUS CHRONIC DISEASES ARE THE GREATEST CAUSE OF DEATH IN THE WORLD. EPIDEMICS OF METABOLIC DISEASES (E.G., CARDIOVASCULAR DISEASES, TYPE 2 DIABETES, OBESITY, METABOLIC SYNDROME AND CERTAIN CANCERS) HAVE BECOME MAJOR CONTRIBUTORS TO THE BURDEN OF POOR HEALTH AND THEY ARE PRESENTLY EMERGING OR ACCELERATING, IN MOST DEVELOPING COUNTRIES. ONE MAJOR LIFESTYLE CONSEQUENCE IS LIGHT AT NIGHT AND SUBSEQUENT DISRUPTED CIRCADIAN RHYTHMS COMMONLY REFERRED TO AS CIRCADIAN DISRUPTION OR CHRONODISRUPTION. MOUNTING EVIDENCE REVEALS THAT PARTICULARLY MELATONIN RHYTHMICITY HAS CRUCIAL ROLES IN A VARIETY OF METABOLIC FUNCTIONS AS AN ANTI-OXIDANT, ANTI-INFLAMMATORY CHRONOBIOTIC AND POSSIBLY AS AN EPIGENETIC REGULATOR. THIS PAPER PROVIDES A BRIEF OUTLINE ABOUT METABOLIC DYSREGULATION IN CONJUNCTION WITH A DISRUPTED MELATONIN RHYTHM. 2009 15 4589 33 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 16 2343 31 EPIGENETIC REGULATION OF MACROPHAGE POLARIZATION IN CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES (CVDS) ARE THE LEADING CAUSE OF HOSPITALIZATION AND DEATH WORLDWIDE, ESPECIALLY IN DEVELOPING COUNTRIES. THE INCREASED PREVALENCE RATE AND MORTALITY DUE TO CVDS, DESPITE THE DEVELOPMENT OF SEVERAL APPROACHES FOR PREVENTION AND TREATMENT, ARE ALARMING TRENDS IN GLOBAL HEALTH. CHRONIC INFLAMMATION AND MACROPHAGE INFILTRATION ARE KEY REGULATORS OF THE INITIATION AND PROGRESSION OF CVDS. RECENT DATA SUGGEST THAT EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLATION, POSTTRANSLATIONAL HISTONE MODIFICATIONS, AND RNA MODIFICATIONS, REGULATE CELL DEVELOPMENT, DNA DAMAGE REPAIR, APOPTOSIS, IMMUNITY, CALCIUM SIGNALING, AND AGING IN CARDIOMYOCYTES; AND ARE INVOLVED IN MACROPHAGE POLARIZATION AND CONTRIBUTE SIGNIFICANTLY TO CARDIAC DISEASE DEVELOPMENT. CARDIAC MACROPHAGES NOT ONLY TRIGGER DAMAGING INFLAMMATORY RESPONSES DURING ATHEROSCLEROTIC PLAQUE FORMATION, MYOCARDIAL INJURY, AND HEART FAILURE BUT ARE ALSO INVOLVED IN TISSUE REPAIR, REMODELING, AND REGENERATION. IN THIS REVIEW, WE SUMMARIZE THE KEY EPIGENETIC MODIFICATIONS THAT INFLUENCE MACROPHAGE POLARIZATION AND CONTRIBUTE TO THE PATHOPHYSIOLOGY OF CVDS, AND HIGHLIGHT THEIR POTENTIAL FOR THE DEVELOPMENT OF ADVANCED EPIGENETIC THERAPIES. 2023 17 4120 40 MECHANISMS OF CARDIOVASCULAR DISORDERS IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A PROCESS RELATED TO ACCELERATED SENESCENCE. CARDIOVASCULAR DISEASES (CVDS), ESPECIALLY THOSE INVOLVING A SYSTEMIC INFLAMMATORY PROCESS SUCH AS ATHEROSCLEROSIS, REMAIN THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD). CKD IS A SYSTEMIC CONDITION AFFECTING APPROXIMATELY 10% OF THE GENERAL POPULATION. THE PREVALENCE OF CKD HAS INCREASED OVER THE PAST DECADES BECAUSE OF THE AGING OF THE POPULATION WORLDWIDE. INDEED, CVDS IN PATIENTS WITH CKD CONSTITUTE A PREMATURE FORM OF CVD OBSERVED IN THE GENERAL POPULATION. MULTIPLE STUDIES INDICATE THAT PATIENTS WITH RENAL DISEASE UNDERGO ACCELERATED AGING, WHICH PRECIPITATES THE APPEARANCE OF PATHOLOGIES, INCLUDING CVDS, USUALLY ASSOCIATED WITH ADVANCED AGE. IN THIS REVIEW, WE DISCUSS SEVERAL ASPECTS THAT CHARACTERIZE CKD-ASSOCIATED CVDS, SUCH AS ETIOPATHOGENIC ELEMENTS THAT CKD PATIENTS SHARE WITH THE GENERAL POPULATION, CHANGES IN THE CELLULAR BALANCE OF REACTIVE OXYGEN SPECIES (ROS), AND THE ASSOCIATED PROCESS OF CELLULAR SENESCENCE. UREMIA-ASSOCIATED AGING IS LINKED WITH NUMEROUS CHANGES AT THE CELLULAR AND MOLECULAR LEVEL. THESE CHANGES ARE SIMILAR TO THOSE OBSERVED IN THE NORMAL PROCESS OF PHYSIOLOGIC AGING. WE ALSO DISCUSS NEW PERSPECTIVES IN THE STUDY OF CKD-ASSOCIATED CVDS AND EPIGENETIC ALTERATIONS IN INTERCELLULAR SIGNALING, MEDIATED BY MICRORNAS AND/OR EXTRACELLULAR VESICLES (EVS), WHICH PROMOTE VASCULAR DAMAGE AND SUBSEQUENT DEVELOPMENT OF CVD. UNDERSTANDING THE PROCESSES AND FACTORS INVOLVED IN ACCELERATED SENESCENCE AND OTHER ABNORMAL INTERCELLULAR SIGNALING WILL IDENTIFY NEW THERAPEUTIC TARGETS AND LEAD TO IMPROVED METHODS OF DIAGNOSIS AND MONITORING FOR PATIENTS WITH CKD-ASSOCIATED CVDS. 2020 18 6607 55 TYPE 2 DIABETES MELLITUS AND CARDIOVASCULAR DISEASE: GENETIC AND EPIGENETIC LINKS. TYPE 2 DIABETES MELLITUS (DM) IS A COMMON METABOLIC DISORDER PREDISPOSING TO DIABETIC CARDIOMYOPATHY AND ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (CVD), WHICH COULD LEAD TO HEART FAILURE THROUGH A VARIETY OF MECHANISMS, INCLUDING MYOCARDIAL INFARCTION AND CHRONIC PRESSURE OVERLOAD. PATHOGENETIC MECHANISMS, MAINLY LINKED TO HYPERGLYCEMIA AND CHRONIC SUSTAINED HYPERINSULINEMIA, INCLUDE CHANGES IN METABOLIC PROFILES, INTRACELLULAR SIGNALING PATHWAYS, ENERGY PRODUCTION, REDOX STATUS, INCREASED SUSCEPTIBILITY TO ISCHEMIA, AND EXTRACELLULAR MATRIX REMODELING. THE CLOSE RELATIONSHIP BETWEEN TYPE 2 DM AND CVD HAS LED TO THE COMMON SOIL HYPOTHESIS, POSTULATING THAT BOTH CONDITIONS SHARE COMMON GENETIC AND ENVIRONMENTAL FACTORS INFLUENCING THIS ASSOCIATION. HOWEVER, ALTHOUGH THE COMMON RISK FACTORS OF BOTH CVD AND TYPE 2 DM, SUCH AS OBESITY, INSULIN RESISTANCE, DYSLIPIDEMIA, INFLAMMATION, AND THROMBOPHILIA, CAN BE IDENTIFIED IN THE MAJORITY OF AFFECTED PATIENTS, LESS IS KNOWN ABOUT HOW THESE FACTORS INFLUENCE BOTH CONDITIONS, SO THAT EFFORTS ARE STILL NEEDED FOR A MORE COMPREHENSIVE UNDERSTANDING OF THIS RELATIONSHIP. THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL BACKGROUNDS OF BOTH TYPE 2 DM AND CVD HAVE BEEN MORE RECENTLY STUDIED AND UPDATED. HOWEVER, THE UNDERLYING PATHOGENETIC MECHANISMS HAVE SELDOM BEEN INVESTIGATED WITHIN THE BROADER SHARED BACKGROUND, BUT RATHER STUDIED IN THE SPECIFIC CONTEXT OF TYPE 2 DM OR CVD, SEPARATELY. AS THE PRECISE PATHOPHYSIOLOGICAL LINKS BETWEEN TYPE 2 DM AND CVD ARE NOT ENTIRELY UNDERSTOOD AND MANY ASPECTS STILL REQUIRE ELUCIDATION, AN INTEGRATED DESCRIPTION OF THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL INFLUENCES INVOLVED IN THE CONCOMITANT DEVELOPMENT OF BOTH DISEASES IS OF PARAMOUNT IMPORTANCE TO SHED NEW LIGHT ON THE INTERLINKS BETWEEN TYPE 2 DM AND CVD. THIS REVIEW ADDRESSES THE CURRENT KNOWLEDGE OF OVERLAPPING GENETIC AND EPIGENETIC ASPECTS IN TYPE 2 DM AND CVD, INCLUDING MICRORNAS AND LONG NON-CODING RNAS, WHOSE ABNORMAL REGULATION HAS BEEN IMPLICATED IN BOTH DISEASE CONDITIONS, EITHER ETIOLOGICALLY OR AS CAUSE FOR THEIR PROGRESSION. UNDERSTANDING THE LINKS BETWEEN THESE DISORDERS MAY HELP TO DRIVE FUTURE RESEARCH TOWARD AN INTEGRATED PATHOPHYSIOLOGICAL APPROACH AND TO PROVIDE FUTURE DIRECTIONS IN THE FIELD. 2018 19 6413 24 THE STATE OF ART OF REGENERATIVE THERAPY IN CARDIOVASCULAR ISCHEMIC DISEASE: BIOLOGY, SIGNALING PATHWAYS, AND EPIGENETICS OF ENDOTHELIAL PROGENITOR CELLS. ISCHEMIC HEART DISEASE IS CURRENTLY A MAJOR CAUSE OF MORTALITY AND MORBIDITY WORLDWIDE. NEVERTHELESS, THE ACTUAL THERAPEUTIC SCENARIO DOES NOT TARGET MYOCARDIAL CELL REGENERATION AND CONSEQUENTLY, THE PROGRESSION TOWARD THE LATE STAGE OF CHRONIC HEART FAILURE IS COMMON. ENDOTHELIAL PROGENITOR CELLS (EPCS) ARE BONE MARROW-DERIVED STEM CELLS THAT CONTRIBUTE TO THE HOMEOSTASIS OF THE ENDOTHELIAL WALL IN ACUTE AND CHRONIC ISCHEMIC DISEASE. CALCIUM MODULATION AND OTHER MOLECULAR PATHWAYS (NOTCH, VEGFR, AND CXCR4) CONTRIBUTE TO EPC PROLIFERATION AND DIFFERENTIATION. THE PRESENT REVIEW PROVIDES A SUMMARY OF EPC BIOLOGY WITH A PARTICULAR FOCUS ON THE REGULATORY PATHWAYS OF EPCS AND DESCRIBES PROMISING APPLICATIONS FOR CARDIOVASCULAR CELL THERAPY. 2020 20 4715 32 NON-CODING RNA REGULATION OF T CELL BIOLOGY: IMPLICATIONS FOR AGE-ASSOCIATED CARDIOVASCULAR DISEASES. PREVALENCE OF AGE-ASSOCIATED CARDIOVASCULAR DISEASES (CVD) HAS DRAMATICALLY INCREASED AS A RESULT OF IMPROVEMENTS IN LIFE EXPECTANCY. CHRONIC INFLAMMATION IS A SHARED PATHOPHYSIOLOGICAL FEATURE OF AGE-ASSOCIATED CVDS, INDICATING A ROLE FOR THE IMMUNE SYSTEM IN THE ONSET AND DEVELOPMENT OF CVDS. INDEED, AGEING ELICITS PROFOUND CHANGES IN BOTH THE CARDIOVASCULAR AND IMMUNE SYSTEM, ESPECIALLY IN THE T CELL COMPARTMENT. ALTHOUGH SUCH CHANGES HAVE BEEN WELL DESCRIBED AT THE CELLULAR LEVEL, THE MOLECULAR MECHANISMS UNDERLYING IMMUNE-MEDIATED CARDIOVASCULAR AGEING REMAIN LARGELY UNEXPLORED. NON-CODING RNAS (NCRNAS) COMPRISE A HETEROGENEOUS FAMILY OF RNA TRANSCRIPTS THAT REGULATE GENE EXPRESSION AT THE EPIGENETIC, TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND POST-TRANSLATIONAL LEVELS. NON-CODING RNAS HAVE RECENTLY EMERGED AS MASTER MODULATORS OF T CELL IMMUNITY. IN THIS REVIEW, THE STATE-OF-THE-ART KNOWLEDGE ON NCRNA REGULATORY EFFECTS OVER T CELL DIFFERENTIATION, FUNCTION, AND AGEING IN THE CONTEXT OF AGE-ASSOCIATED CVDS, SUCH AS ATHEROSCLEROSIS, ACUTE CORONARY SYNDROMES, AND HEART FAILURE, IS DISCUSSED. 2018