1 5672 128 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 2 5724 39 SKELETAL MUSCLE WASTING AND ITS RELATIONSHIP WITH OSTEOARTHRITIS: A MINI-REVIEW OF MECHANISMS AND CURRENT INTERVENTIONS. PURPOSE OF REVIEW: OSTEOARTHRITIS (OA) IS A SUBSET OF JOINT DISORDERS RESULTING IN DEGENERATION OF SYNOVIAL JOINTS. THIS LEADS TO PAIN, DISABILITY AND LOSS OF INDEPENDENCE. KNEE AND HIP OA ARE EXTREMELY PREVALENT, AND THEIR OCCURRENCE INCREASES WITH AGEING. SIMILARLY, LOSS OF MUSCLE MASS AND FUNCTION, SARCOPENIA, OCCURS DURING AGEING. RECENT FINDINGS: LITTLE IS KNOWN ABOUT THE IMPACT OF MUSCLE WASTING ON OA PROGRESSION; NEVERTHELESS, IT HAS BEEN SUGGESTED THAT MUSCLE WASTING DIRECTLY AFFECTS THE STABILITY OF THE JOINTS AND LOSS OF MOBILITY LEADS TO GRADUAL DEGENERATION OF ARTICULAR CARTILAGE. THE MOLECULAR MECHANISMS UNDERLYING MUSCLE WASTING IN OA ARE NOT WELL UNDERSTOOD; HOWEVER, THESE ARE PROBABLY RELATED TO CHANGES IN GENE EXPRESSION, AS WELL AS EPIGENETIC MODIFICATIONS. IT IS BECOMING CLEAR THAT SKELETAL MUSCLE WASTING PLAYS AN IMPORTANT ROLE IN OA DEVELOPMENT AND/OR PROGRESSION. HERE, WE DISCUSS MECHANISMS, CURRENT INTERVENTIONS, SUCH AS EXERCISE, AND POTENTIALLY NOVEL APPROACHES, SUCH AS MODULATION OF MICRORNAS, AIMING AT AMELIORATING OA SYMPTOMS THROUGH MAINTAINING MUSCLE MASS AND FUNCTION. 2019 3 792 43 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 4 4122 34 MECHANISMS OF DEVELOPMENT OF MULTIMORBIDITY IN THE ELDERLY. IN AGEING POPULATIONS MANY PATIENTS HAVE MULTIPLE DISEASES CHARACTERISED BY ACCELERATION OF THE NORMAL AGEING PROCESS. BETTER UNDERSTANDING OF THE SIGNALLING PATHWAYS AND CELLULAR EVENTS INVOLVED IN AGEING SHOWS THAT THESE ARE CHARACTERISTIC OF MANY CHRONIC DEGENERATIVE DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), CHRONIC CARDIOVASCULAR AND METABOLIC DISEASES, AND NEURODEGENERATION. COMMON MECHANISMS HAVE NOW BEEN IDENTIFIED IN THESE DISEASES, WHICH SHOW EVIDENCE OF CELLULAR SENESCENCE WITH TELOMERE SHORTENING, ACTIVATION OF PI3K-AKT-MTOR SIGNALLING, IMPAIRED AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, STEM CELL EXHAUSTION, EPIGENETIC CHANGES, ABNORMAL MICRORNA PROFILES, IMMUNOSENESCENCE AND LOW GRADE CHRONIC INFLAMMATION ("INFLAMMAGING"). MANY OF THESE PATHWAYS ARE DRIVEN BY CHRONIC OXIDATIVE STRESS. THERE IS ALSO A REDUCTION IN ANTI-AGEING MOLECULES, SUCH AS SIRTUINS AND KLOTHO, WHICH FURTHER ACCELERATES THE AGEING PROCESS. UNDERSTANDING THESE MOLECULAR MECHANISMS HAS IDENTIFIED SEVERAL NOVEL THERAPEUTIC TARGETS AND SEVERAL DRUGS HAVE ALREADY BEEN DEVELOPED THAT MAY SLOW THE AGEING PROCESS, AS WELL AS LIFESTYLE INTERVENTIONS, SUCH AS DIET AND PHYSICAL ACTIVITY. THIS INDICATES THAT IN THE FUTURE NEW TREATMENT APPROACHES MAY TARGET THE COMMON PATHWAYS INVOLVED IN MULTIMORBIDITY AND THIS AREA OF RESEARCH SHOULD BE GIVEN HIGH PRIORITY. THUS, COPD SHOULD BE CONSIDERED AS A COMPONENT OF MULTIMORBIDITY AND COMMON DISEASE PATHWAYS, PARTICULARLY ACCELERATED AGEING, SHOULD BE TARGETED. 2015 5 4410 34 MOLECULAR AND BIOLOGICAL PATHWAYS OF SKELETAL MUSCLE DYSFUNCTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WILL BE A MAJOR LEADING CAUSE OF DEATH WORLDWIDE IN THE NEAR FUTURE. WEAKNESS AND ATROPHY OF THE QUADRICEPS ARE ASSOCIATED WITH A SIGNIFICANTLY POORER PROGNOSIS AND INCREASED MORTALITY IN COPD. DESPITE THAT SKELETAL MUSCLE DYSFUNCTION MAY AFFECT BOTH RESPIRATORY AND LIMB MUSCLE GROUPS IN COPD, THE LATTER ARE FREQUENTLY MORE SEVERELY AFFECTED. THEREFORE, MUSCLE DYSFUNCTION IN COPD IS A COMMON SYSTEMIC MANIFESTATION THAT SHOULD BE EVALUATED ON ROUTINE BASIS IN CLINICAL SETTINGS. IN THE PRESENT REVIEW, SEVERAL ASPECTS OF COPD MUSCLE DYSFUNCTION ARE BEING REVIEWED, WITH SPECIAL EMPHASIS ON THE UNDERLYING BIOLOGICAL MECHANISMS. FIGURES ON THE PREVALENCE OF COPD MUSCLE DYSFUNCTION AND THE MOST RELEVANT ETIOLOGIC CONTRIBUTORS ARE ALSO PROVIDED. DESPITE THAT ONGOING RESEARCH WILL SHED LIGHT INTO THE CONTRIBUTION OF ADDITIONAL MECHANISMS TO COPD MUSCLE DYSFUNCTION, CURRENT KNOWLEDGE POINTS TOWARD THE INVOLVEMENT OF A WIDE SPECTRUM OF CELLULAR AND MOLECULAR EVENTS THAT ARE DIFFERENTIALLY EXPRESSED IN RESPIRATORY AND LIMB MUSCLES. SUCH MECHANISMS ARE THOROUGHLY DESCRIBED IN THE ARTICLE. THE CONTRIBUTION OF EPIGENETIC EVENTS ON COPD MUSCLE DYSFUNCTION IS ALSO REVIEWED. WE CONCLUDE THAT IN VIEW OF THE LATEST DISCOVERIES, FROM NOW, ON NEW AVENUES OF RESEARCH SHOULD BE DESIGNED TO SPECIFICALLY TARGET CELLULAR MECHANISMS AND PATHWAYS THAT IMPAIR MUSCLE MASS AND FUNCTION IN COPD USING PHARMACOLOGICAL STRATEGIES AND/OR EXERCISE TRAINING MODALITIES. 2016 6 6360 36 THE ROLE OF INFLAMMATORY PATHWAYS IN CANCER-ASSOCIATED CACHEXIA AND RADIATION RESISTANCE. DYSREGULATED INFLAMMATORY RESPONSES ARE KEY CONTRIBUTORS TO A MULTITUDE OF CHRONIC AILMENTS, INCLUDING CANCER. EVIDENCE INDICATES THAT DISEASE PROGRESSION IN CANCER IS DEPENDENT ON THE COMPLEX INTERACTION BETWEEN THE TUMOR AND THE HOST MICROENVIRONMENT. MOST RECENTLY, THE INFLAMMATORY RESPONSE HAS BEEN SUGGESTED TO BE CRITICAL, AS BOTH THE TUMOR AND MICROENVIRONMENT COMPARTMENTS PRODUCE CYTOKINES THAT ACT ON NUMEROUS TARGET SITES, WHERE THEY FOSTER A COMPLEX CASCADE OF BIOLOGIC OUTCOMES. PATIENTS WITH CANCER-ASSOCIATED CACHEXIA (CAC) SUFFER FROM A DRAMATIC LOSS OF SKELETAL MUSCLE AND ADIPOSE TISSUE, ULTIMATELY PRECLUDING THEM FROM MANY FORMS OF THERAPEUTIC INTERVENTION, INCLUDING RADIOTHERAPY. THE CYTOKINES THAT HAVE BEEN LINKED TO THE PROMOTION OF THE CACHECTIC RESPONSE MAY ALSO PARTICIPATE IN RADIATION RESISTANCE. THE MAJOR CHANGES AT THE CYTOKINE LEVEL ARE, IN PART, DUE TO TRANSCRIPTIONAL REGULATORY ALTERATIONS POSSIBLY DUE TO EPIGENETIC MODIFICATIONS. HEREIN WE DISCUSS THE ROLE OF INFLAMMATORY PATHWAYS IN CAC AND EXAMINE THE POTENTIAL LINK BETWEEN CACHEXIA INDUCTION AND RADIATION RESISTANCE. 2013 7 5263 40 PROMISING BIOMARKERS OF HUMAN AGING: IN SEARCH OF A MULTI-OMICS PANEL TO UNDERSTAND THE AGING PROCESS FROM A MULTIDIMENSIONAL PERSPECTIVE. THE AGING PROCESS HAS BEEN LINKED TO THE OCCURRENCE OF CHRONIC DISEASES AND FUNCTIONAL IMPAIRMENTS, INCLUDING CANCER, SARCOPENIA, FRAILTY, METABOLIC, CARDIOVASCULAR, AND NEURODEGENERATIVE DISEASES. NONETHELESS, AGING IS HIGHLY VARIABLE AND HETEROGENEOUS AND REPRESENTS A CHALLENGE FOR ITS CHARACTERIZATION. IN THIS SENSE, INTRINSIC CAPACITY (IC) STANDS AS A NOVEL PERSPECTIVE BY THE WORLD HEALTH ORGANIZATION, WHICH INTEGRATES THE INDIVIDUAL WELLBEING, ENVIRONMENT, AND RISK FACTORS TO UNDERSTAND AGING. HOWEVER, THERE IS A LACK OF QUANTITATIVE AND QUALITATIVE ATTRIBUTES TO DEFINE IT OBJECTIVELY. THEREFORE, IN THIS REVIEW WE ATTEMPT TO SUMMARIZE THE MOST RELEVANT AND PROMISING BIOMARKERS DESCRIBED IN CLINICAL STUDIES AT DATE OVER DIFFERENT MOLECULAR LEVELS, INCLUDING EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS, AND THE MICROBIOME. TO AID GERONTOLOGISTS, GERIATRICIANS, AND BIOMEDICAL RESEARCHERS TO UNDERSTAND THE AGING PROCESS THROUGH THE IC. AGING BIOMARKERS REFLECT THE PHYSIOLOGICAL STATE OF INDIVIDUALS AND THE UNDERLYING MECHANISMS RELATED TO HOMEOSTATIC CHANGES THROUGHOUT AN INDIVIDUAL LIFESPAN; THEY DEMONSTRATED THAT AGING COULD BE MEASURED INDEPENDENTLY OF TIME (THAT MAY EXPLAIN ITS HETEROGENEITY) AND TO BE HELPFUL TO PREDICT AGE-RELATED SYNDROMES AND MORTALITY. IN SUMMARY, WE HIGHLIGHT THE AREAS OF OPPORTUNITY AND GAPS OF KNOWLEDGE THAT MUST BE ADDRESSED TO FULLY INTEGRATE BIOMEDICAL FINDINGS INTO CLINICALLY USEFUL TOOLS AND INTERVENTIONS. 2020 8 3834 38 INVOLVEMENTS OF LONG NONCODING RNAS IN OBESITY-ASSOCIATED INFLAMMATORY DISEASES. OBESITY IS ASSOCIATED WITH CHRONIC LOW-GRADE INFLAMMATION THAT AFFECTS THE PHENOTYPE OF MULTIPLE TISSUES AND THEREFORE IS IMPLICATED IN THE DEVELOPMENT AND PROGRESSION OF SEVERAL AGE-RELATED CHRONIC INFLAMMATORY DISORDERS. IMPORTANTLY, A NEW FAMILY OF NONCODING RNAS, TERMED LONG NONCODING RNAS (LNCRNAS), HAVE BEEN IDENTIFIED AS KEY REGULATORS OF INFLAMMATORY SIGNALLING PATHWAYS THAT CAN MEDIATE BOTH PRETRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL GENE REGULATION. FURTHERMORE, SEVERAL LNCRNAS HAVE BEEN IDENTIFIED, WHICH ARE DIFFERENTIALLY EXPRESSED IN MULTIPLE TISSUE TYPES IN INDIVIDUALS WHO ARE OBESE OR IN PRECLINICAL MODELS OF OBESITY. IN THIS REVIEW, WE EXAMINE THE EVIDENCE FOR THE ROLE OF SEVERAL OF THE MOST WELL-STUDIED LNCRNAS IN THE REGULATION OF INFLAMMATORY PATHWAYS ASSOCIATED WITH OBESITY. WE HIGHLIGHT THE EVIDENCE FOR THEIR DIFFERENTIAL EXPRESSION IN THE OBESE STATE AND IN AGE-RELATED CONDITIONS INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES (T2D), SARCOPENIA, OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS, WHERE OBESITY PLAYS A SIGNIFICANT ROLE. DETERMINING THE EXPRESSION AND FUNCTIONAL ROLE OF LNCRNAS IN MEDIATING OBESITY-ASSOCIATED CHRONIC INFLAMMATION WILL ADVANCE OUR UNDERSTANDING OF THE EPIGENETIC REGULATORY PATHWAYS THAT UNDERLIE AGE-RELATED INFLAMMATORY DISEASES AND MAY ALSO ULTIMATELY IDENTIFY NEW TARGETS FOR THERAPEUTIC INTERVENTION. 2021 9 2855 56 FROM INFLAMMAGING TO HEALTHY AGING BY DIETARY LIFESTYLE CHOICES: IS EPIGENETICS THE KEY TO PERSONALIZED NUTRITION? THE PROGRESSIVELY OLDER POPULATION IN DEVELOPED COUNTRIES IS REFLECTED IN AN INCREASE IN THE NUMBER OF PEOPLE SUFFERING FROM AGE-RELATED CHRONIC INFLAMMATORY DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, HEART AND LUNG DISEASES, CANCER, OSTEOPOROSIS, ARTHRITIS, AND DEMENTIA. THE HETEROGENEITY IN BIOLOGICAL AGING, CHRONOLOGICAL AGE, AND AGING-ASSOCIATED DISORDERS IN HUMANS HAVE BEEN ASCRIBED TO DIFFERENT GENETIC AND ENVIRONMENTAL FACTORS (I.E., DIET, POLLUTION, STRESS) THAT ARE CLOSELY LINKED TO SOCIOECONOMIC FACTORS. THE COMMON DENOMINATOR OF THESE FACTORS IS THE INFLAMMATORY RESPONSE. CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION DURING PHYSIOLOGICAL AGING AND IMMUNOSENESCENCE ARE INTERTWINED IN THE PATHOGENESIS OF PREMATURE AGING ALSO DEFINED AS 'INFLAMMAGING.' THE LATTER HAS BEEN ASSOCIATED WITH FRAILTY, MORBIDITY, AND MORTALITY IN ELDERLY SUBJECTS. HOWEVER, IT IS UNKNOWN TO WHAT EXTENT INFLAMMAGING OR LONGEVITY IS CONTROLLED BY EPIGENETIC EVENTS IN EARLY LIFE. TODAY, HUMAN DIET IS BELIEVED TO HAVE A MAJOR INFLUENCE ON BOTH THE DEVELOPMENT AND PREVENTION OF AGE-RELATED DISEASES. MOST PLANT-DERIVED DIETARY PHYTOCHEMICALS AND MACRO- AND MICRONUTRIENTS MODULATE OXIDATIVE STRESS AND INFLAMMATORY SIGNALING AND REGULATE METABOLIC PATHWAYS AND BIOENERGETICS THAT CAN BE TRANSLATED INTO STABLE EPIGENETIC PATTERNS OF GENE EXPRESSION. THEREFORE, DIET INTERVENTIONS DESIGNED FOR HEALTHY AGING HAVE BECOME A HOT TOPIC IN NUTRITIONAL EPIGENOMIC RESEARCH. INCREASING EVIDENCE HAS REVEALED THAT COMPLEX INTERACTIONS BETWEEN FOOD COMPONENTS AND HISTONE MODIFICATIONS, DNA METHYLATION, NON-CODING RNA EXPRESSION, AND CHROMATIN REMODELING FACTORS INFLUENCE THE INFLAMMAGING PHENOTYPE AND AS SUCH MAY PROTECT OR PREDISPOSE AN INDIVIDUAL TO MANY AGE-RELATED DISEASES. REMARKABLY, HUMANS PRESENT A BROAD RANGE OF RESPONSES TO SIMILAR DIETARY CHALLENGES DUE TO BOTH GENETIC AND EPIGENETIC MODULATIONS OF THE EXPRESSION OF TARGET PROTEINS AND KEY GENES INVOLVED IN THE METABOLISM AND DISTRIBUTION OF THE DIETARY CONSTITUENTS. HERE, WE WILL SUMMARIZE THE EPIGENETIC ACTIONS OF DIETARY COMPONENTS, INCLUDING PHYTOCHEMICALS, AND MACRO- AND MICRONUTRIENTS AS WELL AS METABOLITES, THAT CAN ATTENUATE INFLAMMAGING. WE WILL DISCUSS THE CHALLENGES FACING PERSONALIZED NUTRITION TO TRANSLATE HIGHLY VARIABLE INTERINDIVIDUAL EPIGENETIC DIET RESPONSES TO POTENTIAL INDIVIDUAL HEALTH BENEFITS/RISKS RELATED TO AGING DISEASE. 2015 10 1871 39 EMERGING ROLE OF EPIGENETICS IN EXPLAINING RELATIONSHIP OF PERIODONTITIS AND CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES SUCH AS ISCHEMIC HEART DISEASES OR STROKE ARE AMONG THE LEADING CAUSE OF DEATHS GLOBALLY, AND EVIDENCE SUGGESTS THAT THESE DISEASES ARE MODULATED BY A MULTIFACTORIAL AND COMPLEX INTERPLAY OF GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. GENETIC PREDISPOSITION AND CHRONIC EXPOSURE TO MODIFIABLE RISK FACTORS HAVE BEEN EXPLORED TO BE INVOLVED IN THE PATHOPHYSIOLOGY OF CVD. ENVIRONMENTAL FACTORS CONTRIBUTE TO AN INDIVIDUAL'S PROPENSITY TO DEVELOP MAJOR CARDIOVASCULAR RISK FACTORS THROUGH EPIGENETIC MODIFICATIONS OF DNA AND HISTONES VIA MIRNA REGULATION OF PROTEIN TRANSLATION THAT ARE TYPES OF EPIGENETIC MECHANISMS AND PARTICIPATE IN DISEASE DEVELOPMENT. PERIODONTAL DISEASE (PD) IS ONE OF THE MOST COMMON ORAL DISEASES IN HUMANS THAT IS CHARACTERIZED BY LOW-GRADE INFLAMMATION AND HAS BEEN SHOWN TO INCREASE THE RISK OF CVDS. RISK FACTORS INVOLVED IN PD AND CVD ARE DETERMINED BOTH GENETICALLY AND BEHAVIORALLY. PERIODONTAL DISEASES SUCH AS CHRONIC INFLAMMATION PROMOTE DNA METHYLATION. EPIGENETIC MODIFICATIONS INVOLVED IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS PLAY AN ESSENTIAL ROLE IN PLAQUE DEVELOPMENT AND VULNERABILITY. EPIGENETICS HAS OPENED A NEW WORLD TO UNDERSTAND AND MANAGE HUMAN DISEASES, INCLUDING CVDS AND PERIODONTAL DISEASES. GENETIC MEDICINE HAS STARTED A NEW ERA OF EPIGENETICS TO OVERCOME HUMAN DISEASES WITH VARIOUS NEW METHODOLOGY. EPIGENETIC PROFILING MAY AID IN BETTER DIAGNOSIS AND STRATIFICATION OF PATIENTS SHOWING POTENTIAL PREDISPOSED STATES FOR DISEASE. A BETTER UNDERSTANDING OF THE EXACT REGULATORY MECHANISMS OF EPIGENETIC PATHWAYS DRIVING INFLAMMATION IS SLOWLY EMERGING AND WILL AID IN DEVELOPING NOVEL TOOLS FOR THE TREATMENT OF DISEASE. 2021 11 2333 35 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 12 4425 43 MOLECULAR BASIS OF AGEING IN CHRONIC METABOLIC DISEASES. AIM: OVER THE LAST DECADES, THE SHIFT IN AGE DISTRIBUTION TOWARDS OLDER AGES AND THE PROGRESSIVE AGEING WHICH HAS OCCURRED IN MOST POPULATIONS HAVE BEEN PARALLELED BY A GLOBAL EPIDEMIC OF OBESITY AND ITS RELATED METABOLIC DISORDERS, PRIMARILY, TYPE 2 DIABETES (T2D). DYSFUNCTION OF THE ADIPOSE TISSUE (AT) IS WIDELY RECOGNIZED AS A SIGNIFICANT HALLMARK OF THE AGEING PROCESS THAT, IN TURN, RESULTS IN SYSTEMIC METABOLIC ALTERATIONS. THESE INCLUDE INSULIN RESISTANCE, ACCUMULATION OF ECTOPIC LIPIDS AND CHRONIC INFLAMMATION, WHICH ARE RESPONSIBLE FOR AN ELEVATED RISK OF OBESITY AND T2D ONSET ASSOCIATED TO AGEING. ON THE OTHER HAND, OBESITY AND T2D, THE PARADIGMS OF AT DYSFUNCTION, SHARE MANY PHYSIOLOGICAL CHARACTERISTICS WITH THE AGEING PROCESS, SUCH AS AN INCREASED BURDEN OF SENESCENT CELLS AND EPIGENETIC ALTERATIONS. THUS, THESE CHRONIC METABOLIC DISORDERS MAY REPRESENT A STATE OF ACCELERATED AGEING. MATERIALS AND METHODS: A MORE PRECISE EXPLANATION OF THE FUNDAMENTAL AGEING MECHANISMS THAT OCCUR IN AT AND A DEEPER UNDERSTANDING OF THEIR ROLE IN THE INTERPLAY BETWEEN ACCELERATED AGEING AND AT DYSFUNCTION CAN BE A FUNDAMENTAL LEAP TOWARDS NOVEL THERAPIES THAT ADDRESS THE CAUSES, NOT JUST THE SYMPTOMS, OF OBESITY AND T2D, UTILIZING STRATEGIES THAT TARGET EITHER SENESCENT CELLS OR DNA METHYLATION. RESULTS: IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE PATHWAYS THAT LEAD TO AT DYSFUNCTION IN THE CHRONOLOGICAL AGEING PROCESS AS WELL AS THE PATHOPHYSIOLOGY OF OBESITY AND T2D, EMPHASIZING THE CRITICAL ROLE OF CELLULAR SENESCENCE AND DNA METHYLATION. CONCLUSION: FINALLY, WE HIGHLIGHT THE NEED FOR FURTHER RESEARCH FOCUSED ON TARGETING THESE MECHANISMS. 2020 13 2570 32 EPIGENETICS OF CHRONIC INFLAMMATORY DISEASES. CHRONIC, NONCOMMUNICABLE, AND INFLAMMATION-ASSOCIATED DISEASES REMAIN THE LARGEST CAUSE OF MORBIDITY AND MORTALITY GLOBALLY AND WITHIN THE UNITED STATES. THIS IS MAINLY DUE TO OUR LIMITED UNDERSTANDING OF THE MOLECULAR MECHANISMS THAT UNDERLIE THESE COMPLEX PATHOLOGIES. THE AVAILABLE EVIDENCE INDICATES THAT STUDIES OF EPIGENETICS (TRADITIONALLY DEFINED AS THE HERITABLE CHANGES TO GENE EXPRESSION THAT ARE INDEPENDENT OF CHANGES TO DNA) ARE SIGNIFICANTLY ADVANCING OUR KNOWLEDGE OF THESE INFLAMMATORY CONDITIONS. THIS REVIEW WILL FOCUS ON EPIGENETIC STUDIES OF THREE DISEASES, THAT ARE AMONG THE MOST BURDENSOME GLOBALLY: CARDIOVASCULAR DISEASE, THE NUMBER ONE CAUSE OF DEATHS WORLDWIDE, TYPE 2 DIABETES AND, ALZHEIMER'S DISEASE. THE CURRENT STATUS OF EPIGENETIC RESEARCH, INCLUDING THE ABILITY TO PREDICT DISEASE RISK, AND KEY PATHOPHYSIOLOGICAL DEFECTS ARE DISCUSSED. THE SIGNIFICANCE OF DEFINING THE CONTRIBUTION OF EPIGENETIC DEFECTS TO NONRESOLVING INFLAMMATION AND AGING, EACH ASSOCIATED WITH THESE DISEASES, IS HIGHLIGHTED, AS THESE ARE LIKELY TO PROVIDE NEW INSIGHTS INTO INFLAMMATORY DISEASE PATHOGENESIS. 2019 14 4928 35 PARP-1 AND PARP-2 ACTIVITY IN CANCER-INDUCED CACHEXIA: POTENTIAL THERAPEUTIC IMPLICATIONS. SKELETAL MUSCLE DYSFUNCTION AND MASS LOSS IS A CHARACTERISTIC FEATURE IN PATIENTS WITH CHRONIC DISEASES INCLUDING CANCER AND ACUTE CONDITIONS SUCH AS CRITICAL ILLNESS. MAINTENANCE OF AN ADEQUATE MUSCLE MASS IS CRUCIAL FOR THE PATIENTS' PROGNOSIS IRRESPECTIVE OF THE UNDERLYING CONDITION. MOREOVER, AGING-RELATED SARCOPENIA MAY FURTHER AGGRAVATE THE MUSCLE WASTING PROCESS ASSOCIATED WITH CHRONIC DISEASES AND CANCER. POLY(ADENOSINE DIPHOSPHATE-RIBOSE) POLYMERASE (PARP) ACTIVATION HAS BEEN DEMONSTRATED TO CONTRIBUTE TO THE PATHOPHYSIOLOGY OF MUSCLE MASS LOSS AND DYSFUNCTION IN ANIMAL MODELS OF CANCER-INDUCED CACHEXIA. GENETIC INHIBITION OF PARP ACTIVITY ATTENUATED THE DELETERIOUS EFFECTS SEEN ON DEPLETED MUSCLES IN MOUSE MODELS OF ONCOLOGIC CACHEXIA. IN THE PRESENT MINIREVIEW THE MECHANISMS WHEREBY PARP ACTIVITY INHIBITION MAY IMPROVE MUSCLE MASS AND PERFORMANCE IN MODELS OF CANCER-INDUCED CACHEXIA ARE DISCUSSED. SPECIFICALLY, THE BENEFICIAL EFFECTS OF INHIBITION OF PARP ACTIVITY ON ATTENUATION OF INCREASED OXIDATIVE STRESS, PROTEIN CATABOLISM, POOR MUSCLE ANABOLISM AND MITOCHONDRIAL CONTENT AND EPIGENETIC MODULATION OF MUSCLE PHENOTYPE ARE REVIEWED IN THIS ARTICLE. FINALLY, THE POTENTIAL THERAPEUTIC STRATEGIES OF PHARMACOLOGICAL PARP ACTIVITY INHIBITION FOR THE TREATMENT OF CANCER-INDUCED CACHEXIA ARE ALSO BEING DESCRIBED IN THIS REVIEW. 2018 15 6629 26 UNDERSTANDING THE HUMAN AGING PROTEOME USING EPIDEMIOLOGICAL MODELS. HUMAN AGING IS A COMPLEX MULTIFACTORIAL PROCESS ASSOCIATED WITH A DECLINE OF PHYSICAL AND COGNITIVE FUNCTION AND HIGH SUSCEPTIBILITY TO CHRONIC DISEASES, INFLUENCED BY GENETIC, EPIGENETIC, ENVIRONMENTAL, AND DEMOGRAPHIC FACTORS. THIS CHAPTER WILL PROVIDE AN OVERVIEW ON THE USE OF EPIDEMIOLOGICAL MODELS WITH PROTEOMICS DATA AS A METHOD THAT CAN BE USED TO IDENTIFY FACTORS THAT MODULATE THE AGING PROCESS IN HUMANS. THIS IS DEMONSTRATED WITH PROTEOMICS DATA FROM HUMAN PLASMA AND SKELETAL MUSCLE, WHERE THE COMBINATION WITH EPIDEMIOLOGICAL MODELS IDENTIFIED A SET OF MITOCHONDRIAL, SPLICEOSOME, AND SENESCENCE PROTEINS AS WELL AS THE ROLE OF ENERGETIC PATHWAYS SUCH AS GLYCOLYSIS, AND ELECTRON TRANSPORT PATHWAYS THAT REGULATE THE AGING PROCESS. 2022 16 2505 45 EPIGENETICS AND MUSCLE DYSFUNCTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON, PREVENTABLE, AND TREATABLE DISEASE AND A MAJOR LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. IN COPD, COMORBIDITIES, ACUTE EXACERBATIONS, AND SYSTEMIC MANIFESTATIONS NEGATIVELY INFLUENCE DISEASE SEVERITY AND PROGRESSION REGARDLESS OF THE RESPIRATORY CONDITION. SKELETAL MUSCLE DYSFUNCTION, WHICH IS ONE OF THE COMMONEST SYSTEMIC MANIFESTATIONS IN PATIENTS WITH COPD, HAS A TREMENDOUS IMPACT ON THEIR EXERCISE CAPACITY AND QUALITY OF LIFE. SEVERAL PATHOPHYSIOLOGICAL AND MOLECULAR UNDERLYING MECHANISMS INCLUDING EPIGENETICS (THE PROCESS WHEREBY GENE EXPRESSION IS REGULATED BY HERITABLE MECHANISMS THAT DO NOT AFFECT DNA SEQUENCE) HAVE BEEN SHOWN TO PARTICIPATE IN THE ETIOLOGY OF COPD MUSCLE DYSFUNCTION. THE EPIGENETIC MODIFICATIONS IDENTIFIED SO FAR IN CELLS INCLUDE DNA METHYLATION, HISTONE ACETYLATION AND METHYLATION, AND NONCODING RNAS SUCH AS MICRORNAS. HEREIN, WE FIRST REVIEW THE ROLE OF EPIGENETIC MECHANISMS IN MUSCLE DEVELOPMENT AND ADAPTATION TO ENVIRONMENTAL FACTORS IN SEVERAL MODELS. MOREOVER, THE EPIGENETIC EVENTS REPORTED SO FAR TO BE POTENTIALLY INVOLVED IN MUSCLE DYSFUNCTION AND MASS LOSS OF PATIENTS WITH COPD ARE ALSO DISCUSSED. FURTHERMORE, THE DIFFERENT EXPRESSION PROFILE OF SEVERAL MUSCLE-ENRICHED MICRORNAS IN THE DIAPHRAGM AND VASTUS LATERALIS MUSCLES OF PATIENTS WITH COPD ARE ALSO REVIEWED FROM RESULTS RECENTLY OBTAINED IN OUR GROUP. THE ROLE OF PROTEIN HYPERACETYLATION IN ENHANCED MUSCLE PROTEIN CATABOLISM OF LIMB MUSCLES IS ALSO DISCUSSED. FUTURE RESEARCH SHOULD FOCUS ON THE FULL ELUCIDATION OF THE TRIGGERS OF EPIGENETIC MECHANISMS AND THEIR SPECIFIC DOWNSTREAM BIOLOGICAL PATHWAYS IN COPD MUSCLE DYSFUNCTION AND WASTING. 2015 17 183 30 ACCELERATED VASCULAR AGING IN CHRONIC KIDNEY DISEASE: THE POTENTIAL FOR NOVEL THERAPIES. THE PATHOPHYSIOLOGY OF VASCULAR DISEASE IS LINKED TO ACCELERATED BIOLOGICAL AGING AND A COMBINATION OF GENETIC, LIFESTYLE, BIOLOGICAL, AND ENVIRONMENTAL RISK FACTORS. WITHIN THE SCENARIO OF UNCONTROLLED ARTERY WALL AGING PROCESSES, CKD (CHRONIC KIDNEY DISEASE) STANDS OUT AS A VALID MODEL FOR DETAILED STRUCTURAL, FUNCTIONAL, AND MOLECULAR STUDIES OF THIS PROCESS. THE CARDIORENAL SYNDROME RELATES TO THE DETRIMENTAL BIDIRECTIONAL INTERPLAY BETWEEN THE KIDNEY AND THE CARDIOVASCULAR SYSTEM. IN ADDITION TO ESTABLISHED RISK FACTORS, THIS GROUP OF PATIENTS IS SUBJECTED TO A PLETHORA OF OTHER EMERGING VASCULAR RISK FACTORS, SUCH AS INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VITAMIN K DEFICIENCY, CELLULAR SENESCENCE, SOMATIC MUTATIONS, EPIGENETIC MODIFICATIONS, AND INCREASED APOPTOSIS. A BETTER UNDERSTANDING OF THE MOLECULAR MECHANISMS THROUGH WHICH THE UREMIC MILIEU TRIGGERS AND MAINTAINS EARLY VASCULAR AGING PROCESSES, HAS PROVIDED IMPORTANT NEW CLUES ON INFLAMMATORY PATHWAYS AND EMERGING RISK FACTORS ALIKE, AND TO THE ALTERED BEHAVIOR OF CELLS IN THE ARTERIAL WALL. ADVANCES IN THE UNDERSTANDING OF THE BIOLOGY OF UREMIC EARLY VASCULAR AGING OPENS AVENUES TO NOVEL PHARMACOLOGICAL AND NUTRITIONAL THERAPEUTIC INTERVENTIONS. SUCH STRATEGIES HOLD PROMISE TO IMPROVE FUTURE PREVENTION AND TREATMENT OF EARLY VASCULAR AGING NOT ONLY IN CKD BUT ALSO IN THE ELDERLY GENERAL POPULATION. 2023 18 1112 39 COMMON PATHOGENETIC MECHANISMS UNDERLYING AGING AND TUMOR AND MEANS OF INTERVENTIONS. RECENTLY, THERE HAS BEEN AN INCREASE IN THE INCIDENCE OF MALIGNANT TUMORS AMONG THE OLDER POPULATION. MOREOVER, THERE IS AN ASSOCIATION BETWEEN AGING AND CANCER. DURING THE PROCESS OF SENESCENCE, THE HUMAN BODY SUFFERS FROM A SERIES OF IMBALANCES, WHICH HAVE BEEN SHOWN TO FURTHER ACCELERATE AGING, TRIGGER TUMORIGENESIS, AND FACILITATE CANCER PROGRESSION. THEREFORE, EXPLORING THE JUNCTIONS OF AGING AND CANCER AND SEARCHING FOR NOVEL METHODS TO RESTORE THE JUNCTIONS IS OF GREAT IMPORTANCE TO INTERVENE AGAINST AGING-RELATED CANCERS. IN THIS REVIEW, WE HAVE IDENTIFIED THE UNDERLYING PATHOGENETIC MECHANISMS OF AGING-RELATED CANCERS BY COMPARING ALTERATIONS IN THE HUMAN BODY CAUSED BY AGING AND THE FACTORS THAT TRIGGER CANCERS. WE FOUND THAT THE COMMON MECHANISMS OF AGING AND CANCER INCLUDE CELLULAR SENESCENCE, ALTERATIONS IN PROTEOSTASIS, MICROBIOTA DISORDERS (DECREASED PROBIOTICS AND INCREASED PERNICIOUS BACTERIA), PERSISTENT CHRONIC INFLAMMATION, EXTENSIVE IMMUNOSENESCENCE, INORDINATE ENERGY METABOLISM, ALTERED MATERIAL METABOLISM, ENDOCRINE DISORDERS, ALTERED GENETIC EXPRESSION, AND EPIGENETIC MODIFICATION. FURTHERMORE, WE HAVE PROPOSED THAT AGING AND CANCER HAVE COMMON MEANS OF INTERVENTION, INCLUDING NOVEL USES OF COMMON MEDICINE (METFORMIN, RESVERATROL, AND RAPAMYCIN), DIETARY RESTRICTION, AND ARTIFICIAL MICROBIOTA INTERVENTION OR SELECTIVELY REPLENISHING SCARCE METABOLITES. IN ADDITION, WE HAVE SUMMARIZED THE RESEARCH PROGRESS OF EACH INTERVENTION AND REVEALED THEIR BIDIRECTIONAL EFFECTS ON CANCER PROGRESSION TO COMPARE THEIR RELIABILITY AND FEASIBILITY. THEREFORE, THE STUDY FINDINGS PROVIDE VITAL INFORMATION FOR ADVANCED RESEARCH STUDIES ON AGE-RELATED CANCERS. HOWEVER, THERE IS A NEED FOR FURTHER OPTIMIZATION OF THE DESCRIBED METHODS AND MORE SUITABLE METHODS FOR COMPLICATED CLINICAL PRACTICES. IN CONCLUSION, TARGETING AGING MAY HAVE POTENTIAL THERAPEUTIC EFFECTS ON AGING-RELATED CANCERS. 2022 19 4273 34 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 20 6204 39 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023