1 5968 79 TERPENOID TREATMENT IN OSTEOPOROSIS: THIS IS WHERE WE HAVE COME IN RESEARCH. LOWER BONE RESISTANCE TO LOAD IS DUE TO THE IMBALANCE OF BONE HOMEOSTASIS, WHERE EXCESSIVE BONE RESORPTION, COMPARED WITH BONE FORMATION, DETERMINES A PROGRESSIVE OSTEOPENIA, LEADING TO A HIGH RISK OF FRACTURES AND CONSEQUENT PAIN AND FUNCTIONAL LIMITATIONS. TERPENOIDS, WITH THEIR ACTIVITIES AGAINST BONE RESORPTION, HAVE RECENTLY RECEIVED INCREASED ATTENTION FROM RESEARCHERS. THEY ARE POTENTIALLY MORE SUITABLE FOR LONG-TERM USE COMPARED WITH TRADITIONAL THERAPEUTICS. IN THIS REVIEW OF THE LITERATURE OF THE PAST 5 YEARS, WE PROVIDE COMPREHENSIVE INFORMATION ON TERPENOIDS, WITH THEIR ANTI-OSTEOPOROTIC EFFECTS, HIGHLIGHTING MOLECULAR MECHANISMS THAT ARE OFTEN IN EPIGENETIC KEY AND A POSSIBLE PHARMACOLOGICAL USE IN OSTEOPOROSIS PREVENTION AND TREATMENT. 2021 2 2824 61 FLAVONOIDS IN BONE EROSIVE DISEASES: PERSPECTIVES IN OSTEOPOROSIS TREATMENT. IMBALANCE OF BONE HOMEOSTASIS, WITH EXCESSIVE BONE RESORPTION COMPARED WITH BONE FORMATION, LEADS TO THE DEVELOPMENT OF PROGRESSIVE OSTEOPENIA LEADING TO LOWER BONE RESISTANCE TO LOAD, WITH CONSEQUENT PAIN AND FUNCTIONAL LIMITATIONS. PHYTOCHEMICALS WITH THERAPEUTIC AND PREVENTIVE EFFECTS AGAINST BONE RESORPTION HAVE RECENTLY RECEIVED INCREASING ATTENTION SINCE THEY ARE POTENTIALLY MORE SUITABLE FOR LONG-TERM USE THAN TRADITIONAL THERAPEUTIC CHEMICAL COMPOUNDS. IN THIS SYSTEMATIC REVIEW OF THE LITERATURE OF THE PAST 5 YEARS, COMPREHENSIVE INFORMATION IS PROVIDED ON FLAVONOIDS WITH POTENTIAL ANTIRESORPTION AND PRO-OSTEOGENIC EFFECTS. IT AIMS TO HIGHLIGHT THE MOLECULAR MECHANISMS OF THESE MOLECULES, OFTEN EPIGENETIC, AND THEIR POSSIBLE PHARMACOLOGICAL USE, WHICH IS OF GREAT IMPORTANCE FOR THE PREVENTION AND TREATMENT OF OSTEOPOROSIS (OP). 2021 3 929 16 CHRONIC INFLAMMATION: ACCELERATOR OF BIOLOGICAL AGING. BIOLOGICAL AGING IS CHARACTERIZED BY A CHRONIC LOW-GRADE INFLAMMATION LEVEL. THIS CHRONIC PHENOMENON HAS BEEN NAMED "INFLAMM-AGING" AND IS A HIGHLY SIGNIFICANT RISK FACTOR FOR MORBIDITY AND MORTALITY IN THE OLDER PERSONS. THE MOST COMMON THEORIES OF INFLAMM-AGING INCLUDE REDOX STRESS, MITOCHONDRIAL DYSFUNCTION, GLYCATION, DEREGULATION OF THE IMMUNE SYSTEM, HORMONAL CHANGES, EPIGENETIC MODIFICATIONS, AND DYSFUNCTION TELOMERE ATTRITION. INFLAMM-AGING PLAYS A ROLE IN THE INITIATION AND PROGRESSION OF AGE-RELATED DISEASES SUCH AS TYPE II DIABETES, ALZHEIMER'S DISEASE, CARDIOVASCULAR DISEASE, FRAILTY, SARCOPENIA, OSTEOPOROSIS, AND CANCER. THIS REVIEW WILL COVER THE IDENTIFICATION OF PATHWAYS THAT CONTROL AGE-RELATED INFLAMMATION ACROSS MULTIPLE SYSTEMS AND ITS POTENTIAL CAUSAL ROLE IN CONTRIBUTING TO ADVERSE HEALTH OUTCOMES. 2017 4 2361 17 EPIGENETIC REGULATION OF SKELETAL TISSUE INTEGRITY AND OSTEOPOROSIS DEVELOPMENT. BONE TURNOVER IS SOPHISTICATEDLY BALANCED BY A DYNAMIC COUPLING OF BONE FORMATION AND RESORPTION AT VARIOUS RATES. THE ORCHESTRATION OF THIS CONTINUOUS REMODELING OF THE SKELETON FURTHER AFFECTS OTHER SKELETAL TISSUES THROUGH ORGAN CROSSTALK. CHRONIC EXCESSIVE BONE RESORPTION COMPROMISES BONE MASS AND ITS POROUS MICROSTRUCTURE AS WELL AS PROPER BIOMECHANICS. THIS ACCELERATES THE DEVELOPMENT OF OSTEOPOROTIC DISORDERS, A LEADING CAUSE OF SKELETAL DEGENERATION-ASSOCIATED DISABILITY AND PREMATURE DEATH. BONE-FORMING CELLS PLAY IMPORTANT ROLES IN MAINTAINING BONE DEPOSIT AND OSTEOCLASTIC RESORPTION. A POOR ORGANELLE MACHINERY, SUCH AS MITOCHONDRIAL DYSFUNCTION, ENDOPLASMIC RETICULUM STRESS, AND DEFECTIVE AUTOPHAGY, ETC., DYSREGULATES GROWTH FACTOR SECRETION, MINERALIZATION MATRIX PRODUCTION, OR OSTEOCLAST-REGULATORY CAPACITY IN OSTEOBLASTIC CELLS. A PLETHORA OF EPIGENETIC PATHWAYS REGULATE BONE FORMATION, SKELETAL INTEGRITY, AND THE DEVELOPMENT OF OSTEOPOROSIS. MICRORNAS INHIBIT PROTEIN TRANSLATION BY BINDING THE 3'-UNTRANSLATED REGION OF MRNAS OR PROMOTE TRANSLATION THROUGH POST-TRANSCRIPTIONAL PATHWAYS. DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATION OF HISTONES ALTER THE CHROMATIN STRUCTURE, HINDERING HISTONE ENRICHMENT IN PROMOTER REGIONS. MICRORNA-PROCESSING ENZYMES AND DNA AS WELL AS HISTONE MODIFICATION ENZYMES CATALYZE THESE MODIFYING REACTIONS. GAIN AND LOSS OF THESE EPIGENETIC MODIFIERS IN BONE-FORMING CELLS AFFECT THEIR EPIGENETIC LANDSCAPES, INFLUENCING BONE HOMEOSTASIS, MICROARCHITECTURAL INTEGRITY, AND OSTEOPOROTIC CHANGES. THIS ARTICLE CONVEYS PRODUCTIVE INSIGHTS INTO BIOLOGICAL ROLES OF DNA METHYLATION, MICRORNA, AND HISTONE MODIFICATION AND HIGHLIGHTS THEIR INTERACTIONS DURING SKELETAL DEVELOPMENT AND BONE LOSS UNDER PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS. 2020 5 4870 19 OSTEOPOROSIS: A LIFECOURSE APPROACH. IT IS BECOMING INCREASINGLY APPARENT THAT THE RISK OF DEVELOPING OSTEOPOROSIS IS ACCRUED THROUGHOUT THE ENTIRE LIFECOURSE, EVEN FROM AS EARLY AS CONCEPTION. THUS EARLY GROWTH IS ASSOCIATED WITH BONE MASS AT PEAK AND IN OLDER AGE, AND RISK OF HIP FRACTURE. NOVEL FINDINGS FROM MOTHER-OFFSPRING COHORTS HAVE YIELDED GREATER UNDERSTANDING OF RELATIONSHIPS BETWEEN PATTERNS OF INTRAUTERINE AND POSTNATAL GROWTH IN THE CONTEXT OF LATER BONE DEVELOPMENT. STUDY OF BIOLOGICAL SAMPLES FROM THESE POPULATIONS HAS HELPED CHARACTERIZE POTENTIAL MECHANISTIC UNDERPINNINGS, SUCH AS EPIGENETIC PROCESSES. GLOBAL POLICY HAS RECOGNIZED THE IMPORTANCE OF EARLY GROWTH AND NUTRITION TO THE RISK OF DEVELOPING ADULT CHRONIC NONCOMMUNICABLE DISEASES SUCH AS OSTEOPOROSIS; TESTING OF PREGNANCY INTERVENTIONS AIMED AT OPTIMIZING OFFSPRING BONE HEALTH IS NOW UNDERWAY. IT IS HOPED THAT THROUGH SUCH PROGRAMS, NOVEL PUBLIC HEALTH STRATEGIES MAY BE ESTABLISHED WITH THE ULTIMATE GOAL OF REDUCING THE BURDEN OF OSTEOPOROTIC FRACTURE IN OLDER AGE. 2014 6 5432 18 REJUVENATION OF MESENCHYMAL STEM CELLS TO AMELIORATE SKELETAL AGING. ADVANCED AGE IS A SHARED RISK FACTOR FOR MANY CHRONIC AND DEBILITATING SKELETAL DISEASES INCLUDING OSTEOPOROSIS AND PERIODONTITIS. MESENCHYMAL STEM CELLS DEVELOP VARIOUS AGING PHENOTYPES INCLUDING THE ONSET OF SENESCENCE, INTRINSIC LOSS OF REGENERATIVE POTENTIAL AND EXACERBATION OF INFLAMMATORY MICROENVIRONMENT VIA SECRETORY FACTORS. THIS REVIEW ELABORATES ON THE EMERGING CONCEPTS ON THE MOLECULAR AND EPIGENETIC MECHANISMS OF MSC SENESCENCE, SUCH AS THE ACCUMULATION OF OXIDATIVE STRESS, DNA DAMAGE AND MITOCHONDRIAL DYSFUNCTION. SENESCENT MSCS AGGRAVATE LOCAL INFLAMMATION, DISRUPT BONE REMODELING AND BONE-FAT BALANCE, THEREBY CONTRIBUTING TO THE PROGRESSION OF AGE-RELATED BONE DISEASES. VARIOUS REJUVENATION STRATEGIES TO TARGET SENESCENT MSCS COULD PRESENT A PROMISING PARADIGM TO RESTORE SKELETAL AGING. 2023 7 4396 23 MODULATION OF CHRONIC INFLAMMATION BY QUERCETIN: THE BENEFICIAL EFFECTS ON OBESITY. OBESITY HAS BECOME A MAJOR RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. MOREOVER, OBESITY INDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE VASCULAR SYSTEM. QUERCETIN IS THE MAJOR REPRESENTATIVE OF THE FLAVONOID SUBCLASS OF FLAVONOLS, WHICH IS UBIQUITOUSLY CONTAINED WITHIN NATURAL PLANTS SUCH AS GREEN TEA, AND VEGETABLES, INCLUDING ONIONS AND APPLES. RESEARCHERS HAVE FOCUSED GREATER ATTENTION TO THE BENEFICIAL PHYSIOLOGICAL ROLES OF QUERCETIN, WHICH HAS ANTI-OXIDATIVE, ANTI-INFLAMMATORY, AND ANTI-FIBROTIC EFFECTS ON INSULIN RESISTANCE AND ATHEROSCLEROSIS IN OBESITY-RELATED DISEASES. ALSO, THE ANTI-INFLAMMATORY EFFECTS OF QUERCETIN ON INTESTINAL MICROBIOTA HAVE BEEN DEMONSTRATED IN OBESITY. IN ADDITION, THERE IS INCREASING EVIDENCE THAT QUERCETIN IS ASSOCIATED WITH EPIGENETIC ACTIVITIES IN CANCER, AND IN MATERNAL UNDERNUTRITION DURING GESTATION AND LACTATION. IN THIS REVIEW, WE FOCUS ON THE CHEMICAL PROPERTIES OF QUERCETIN, ITS DIETARY SOURCES IN OBESITY, AND ITS ANTI-INFLAMMATORY EFFECTS ON INSULIN RESISTANCE, ATHEROSCLEROSIS, INTESTINAL MICROBIOTA, AND MATERNAL UNDER-NUTRITION WITH EPIGENETIC ACTIVITY. 2020 8 4211 20 METFORMIN FOR CARDIOVASCULAR PROTECTION, INFLAMMATORY BOWEL DISEASE, OSTEOPOROSIS, PERIODONTITIS, POLYCYSTIC OVARIAN SYNDROME, NEURODEGENERATION, CANCER, INFLAMMATION AND SENESCENCE: WHAT IS NEXT? DIABETES IS ACCOMPANIED BY SEVERAL COMPLICATIONS. HIGHER PREVALENCE OF CANCERS, CARDIOVASCULAR DISEASES, CHRONIC KIDNEY DISEASE (CKD), OBESITY, OSTEOPOROSIS, AND NEURODEGENERATIVE DISEASES HAS BEEN REPORTED AMONG PATIENTS WITH DIABETES. METFORMIN IS THE OLDEST ORAL ANTIDIABETIC DRUG AND CAN IMPROVE COEXISTING COMPLICATIONS OF DIABETES. CLINICAL TRIALS AND OBSERVATIONAL STUDIES UNCOVERED THAT METFORMIN CAN REMARKABLY PREVENT OR ALLEVIATE CARDIOVASCULAR DISEASES, OBESITY, POLYCYSTIC OVARIAN SYNDROME (PCOS), OSTEOPOROSIS, CANCER, PERIODONTITIS, NEURONAL DAMAGE AND NEURODEGENERATIVE DISEASES, INFLAMMATION, INFLAMMATORY BOWEL DISEASE (IBD), TUBERCULOSIS, AND COVID-19. IN ADDITION, METFORMIN HAS BEEN PROPOSED AS AN ANTIAGING AGENT. NUMEROUS MECHANISMS WERE SHOWN TO BE INVOLVED IN THE PROTECTIVE EFFECTS OF METFORMIN. METFORMIN ACTIVATES THE LKB1/AMPK PATHWAY TO INTERACT WITH SEVERAL INTRACELLULAR SIGNALING PATHWAYS AND MOLECULAR MECHANISMS. THE DRUG MODIFIES THE BIOLOGIC FUNCTION OF NF-KAPPAB, PI3K/AKT/MTOR, SIRT1/PGC-1ALPHA, NLRP3, ERK, P38 MAPK, WNT/BETA-CATENIN, NRF2, JNK, AND OTHER MAJOR MOLECULES IN THE INTRACELLULAR SIGNALING NETWORK. IT ALSO REGULATES THE EXPRESSION OF NONCODING RNAS. THEREBY, METFORMIN CAN REGULATE METABOLISM, GROWTH, PROLIFERATION, INFLAMMATION, TUMORIGENESIS, AND SENESCENCE. ADDITIONALLY, METFORMIN MODULATES IMMUNE RESPONSE, AUTOPHAGY, MITOPHAGY, ENDOPLASMIC RETICULUM (ER) STRESS, AND APOPTOSIS AND EXERTS EPIGENETIC EFFECTS. FURTHERMORE, METFORMIN PROTECTS AGAINST OXIDATIVE STRESS AND GENOMIC INSTABILITY, PRESERVES TELOMERE LENGTH, AND PREVENTS STEM CELL EXHAUSTION. IN THIS REVIEW, THE PROTECTIVE EFFECTS OF METFORMIN ON EACH DISEASE WILL BE DISCUSSED USING THE RESULTS OF RECENT META-ANALYSES, CLINICAL TRIALS, AND OBSERVATIONAL STUDIES. THEREAFTER, IT WILL BE METICULOUSLY EXPLAINED HOW METFORMIN REPROGRAMS INTRACELLULAR SIGNALING PATHWAYS AND ALTERS MOLECULAR AND CELLULAR INTERACTIONS TO MODIFY THE CLINICAL PRESENTATIONS OF SEVERAL DISEASES. 2021 9 5919 15 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 5634 24 SENOLYTICS AND SENOMORPHICS: NATURAL AND SYNTHETIC THERAPEUTICS IN THE TREATMENT OF AGING AND CHRONIC DISEASES. CELLULAR SENESCENCE IS A HETEROGENEOUS PROCESS GUIDED BY GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS, CHARACTERIZING MANY TYPES OF SOMATIC CELLS. IT HAS BEEN SUGGESTED AS AN AGING HALLMARK THAT IS BELIEVED TO CONTRIBUTE TO AGING AND CHRONIC DISEASES. SENESCENT CELLS (SC) EXHIBIT A SPECIFIC SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP), MAINLY CHARACTERIZED BY THE PRODUCTION OF PROINFLAMMATORY AND MATRIX-DEGRADING MOLECULES. WHEN SC ACCUMULATE, A CHRONIC, SYSTEMIC, LOW-GRADE INFLAMMATION, KNOWN AS INFLAMMAGING, IS INDUCED. IN TURN, THIS CHRONIC IMMUNE SYSTEM ACTIVATION RESULTS IN REDUCED SC CLEARANCE THUS ESTABLISHING A VICIOUS CIRCLE THAT FUELS INFLAMMAGING. SC ACCUMULATION REPRESENTS A CAUSAL FACTOR FOR VARIOUS AGE-RELATED PATHOLOGIES. TARGETING OF SEVERAL AGING HALLMARKS HAS BEEN SUGGESTED AS A STRATEGY TO AMELIORATE HEALTHSPAN AND POSSIBLY LIFESPAN. CONSEQUENTLY, SC AND SASP ARE VIEWED AS POTENTIAL THERAPEUTIC TARGETS EITHER THROUGH THE SELECTIVE KILLING OF SC OR THE SELECTIVE SASP BLOCKAGE, THROUGH NATURAL OR SYNTHETIC COMPOUNDS. THESE COMPOUNDS ARE MEMBERS OF A FAMILY OF AGENTS CALLED SENOTHERAPEUTICS DIVIDED INTO SENOLYTICS AND SENOMORPHICS. FEW OF THEM ARE ALREADY IN CLINICAL TRIALS, POSSIBLY REPRESENTING A FUTURE TREATMENT OF AGE-RELATED PATHOLOGIES INCLUDING DISEASES SUCH AS ATHEROSCLEROSIS, OSTEOARTHRITIS, OSTEOPOROSIS, CANCER, DIABETES, NEURODEGENERATIVE DISEASES SUCH AS ALZHEIMER'S DISEASE, CARDIOVASCULAR DISEASES, HEPATIC STEATOSIS, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, IDIOPATHIC PULMONARY FIBROSIS AND AGE-RELATED MACULAR DEGENERATION. IN THIS REVIEW, WE PRESENT THE ALREADY IDENTIFIED SENOLYTICS AND SENOMORPHICS FOCUSING ON THEIR REDOX-SENSITIVE PROPERTIES. WE DESCRIBE THE STUDIES THAT REVEALED THEIR EFFECTS ON CELLULAR SENESCENCE AND ENABLED THEIR NOMINATION AS NOVEL ANTI-AGING AGENTS. WE REFER TO THE SENOLYTICS THAT ARE ALREADY IN CLINICAL TRIALS AND WE PRESENT VARIOUS ADVERSE EFFECTS EXHIBITED BY SENOTHERAPEUTICS SO FAR. FINALLY, WE DISCUSS ASPECTS OF THE SENOTHERAPEUTICS THAT NEED IMPROVEMENT AND WE SUGGEST THE DESIGN OF FUTURE SENOTHERAPEUTICS TO TARGET SPECIFIC REDOX-REGULATED SIGNALING PATHWAYS IMPLICATED EITHER IN THE REGULATION OF SASP OR IN THE ELIMINATION OF SC. 2021 11 6786 24 [CONSENSUS AND CONTROVERSY ON RESEARCH PROGRESS AND CLINICAL PRACTICE OF VASCULAR CALCIFICATION]. VASCULAR CALCIFICATION IS AN ACTIVE AND COMPLEX PATHOLOGICAL PROCESS REGULATED BY SEVERAL FACTORS. VASCULAR CALCIFICATION IS CLOSELY RELATED TO THE INCIDENCE AND MORTALITY OF THE CARDIOVASCULAR DISEASE, CHRONIC KIDNEY DISEASE AND OTHER DISEASES, WHICH AFFECTS MULTIPLE ORGANS AND SYSTEMS, THUS AFFECTING PEOPLE'S HEALTH. THEREFORE, MORE AND MORE ATTENTION IS PAID TO VASCULAR CALCIFICATION. AT PRESENT, THE PATHOGENESIS AND CLINICAL PRACTICE OF VASCULAR CALCIFICATION HAVE BEEN CONTINUOUSLY IMPROVED, WHICH MAINLY INCLUDES CALCIUM AND PHOSPHORUS IMBALANCE THEORY, VASCULAR SMOOTH MUSCLE CELL TRANSDIFFERENTIATION THEORY, BONE HOMEOSTASIS IMBALANCE THEORY, EPIGENETIC REGULATION THEORY, INFLAMMATION THEORY, EXTRACELLULAR MATRIX THEORY, NEW CELL FATE THEORY AND SO ON. HOWEVER, THERE ARE STILL MANY UNSOLVED PROBLEMS. SINCE THE OCCURRENCE AND DEVELOPMENT OF VASCULAR CALCIFICATION AFFECT MULTIPLE ORGANS AND SYSTEMS, THIS EXPERT CONSENSUS GATHERED CLINICIANS AND BASIC RESEARCH EXPERTS ENGAGED IN THE STUDY OF VASCULAR CALCIFICATION IN ORDER TO SUMMARIZE THE PROGRESS OF VARIOUS DISCIPLINES RELATED TO VASCULAR CALCIFICATION IN RECENT YEARS. THE PURPOSE OF THIS CONSENSUS IS TO SYSTEMATICALLY SUMMARIZE THE LATEST RESEARCH PROGRESS, TREATMENT CONSENSUS AND CONTROVERSY OF VASCULAR CALCIFICATION FROM THE ASPECTS OF EPIDEMIOLOGY, PATHOGENESIS, PREVENTION AND TREATMENT, SO AS TO PROVIDE THEORETICAL BASIS AND CLINICAL ENLIGHTENMENT FOR IN-DEPTH RESEARCH IN THIS FIELD. 2022 12 6412 30 THE SPECTRUM OF FUNDAMENTAL BASIC SCIENCE DISCOVERIES CONTRIBUTING TO ORGANISMAL AGING. AGING RESEARCH HAS UNDERGONE UNPRECEDENTED ADVANCES AT AN ACCELERATING RATE IN RECENT YEARS, LEADING TO EXCITEMENT IN THE FIELD AS WELL AS OPPORTUNITIES FOR IMAGINATION AND INNOVATION. NOVEL INSIGHTS INDICATE THAT, RATHER THAN RESULTING FROM A PREPROGRAMMED SERIES OF EVENTS, THE AGING PROCESS IS PREDOMINANTLY DRIVEN BY FUNDAMENTAL NON-ADAPTIVE MECHANISMS THAT ARE INTERCONNECTED, LINKED, AND OVERLAP. TO VARYING DEGREES, THESE MECHANISMS ALSO MANIFEST WITH AGING IN BONE WHERE THEY CAUSE SKELETAL FRAGILITY. BECAUSE THESE MECHANISMS OF AGING CAN BE MANIPULATED, IT MIGHT BE POSSIBLE TO SLOW, DELAY, OR ALLEVIATE MULTIPLE AGE-RELATED DISEASES AND THEIR COMPLICATIONS BY TARGETING CONSERVED GENETIC SIGNALING PATHWAYS, CONTROLLED FUNCTIONAL NETWORKS, AND BASIC BIOCHEMICAL PROCESSES. INDEED, FINDINGS IN VARIOUS MAMMALIAN SPECIES SUGGEST THAT TARGETING FUNDAMENTAL AGING MECHANISMS (EG, VIA EITHER LOSS-OF-FUNCTION OR GAIN-OF-FUNCTION MUTATIONS OR ADMINISTRATION OF PHARMACOLOGICAL THERAPIES) CAN EXTEND HEALTHSPAN; IE, THE HEALTHY PERIOD OF LIFE FREE OF CHRONIC DISEASES. IN THIS REVIEW, WE SUMMARIZE THE EVIDENCE SUPPORTING THE ROLE OF THE SPECTRUM OF FUNDAMENTAL BASIC SCIENCE DISCOVERIES CONTRIBUTING TO ORGANISMAL AGING, WITH EMPHASIS ON MAMMALIAN STUDIES AND IN PARTICULAR AGING MECHANISMS IN BONE THAT DRIVE SKELETAL FRAGILITY. THESE MECHANISMS OR AGING HALLMARKS INCLUDE: GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DEREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION. BECAUSE THESE MECHANISMS ARE LINKED, INTERVENTIONS THAT AMELIORATE ONE HALLMARK CAN IN THEORY AMELIORATE OTHERS. IN THE FIELD OF BONE AND MINERAL RESEARCH, CURRENT CHALLENGES INCLUDE DEFINING THE RELATIVE CONTRIBUTIONS OF EACH AGING HALLMARK TO THE NATURAL SKELETAL AGING PROCESS, BETTER UNDERSTANDING THE COMPLEX INTERCONNECTIONS AMONG THE HALLMARKS, AND IDENTIFYING THE MOST EFFECTIVE THERAPEUTIC STRATEGIES TO SAFELY TARGET MULTIPLE HALLMARKS. BASED ON THEIR INTERCONNECTIONS, IT MAY BE FEASIBLE TO SIMULTANEOUSLY INTERFERE WITH SEVERAL FUNDAMENTAL AGING MECHANISMS TO ALLEVIATE A WIDE SPECTRUM OF AGE-RELATED CHRONIC DISEASES, INCLUDING OSTEOPOROSIS. (C) 2018 AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH. 2018 13 5136 21 POTENTIAL MECHANISMS LINKING PSYCHOLOGICAL STRESS TO BONE HEALTH. CHRONIC PSYCHOLOGICAL STRESS AFFECTS MANY BODY SYSTEMS, INCLUDING THE SKELETON, THROUGH VARIOUS MECHANISMS. THIS REVIEW AIMS TO PROVIDE AN OVERVIEW OF THE FACTORS MEDIATING THE RELATIONSHIP BETWEEN PSYCHOLOGICAL STRESS AND BONE HEALTH. THESE FACTORS CAN BE DIVIDED INTO PHYSIOLOGICAL AND BEHAVIOURAL CHANGES INDUCED BY PSYCHOLOGICAL STRESS. THE PHYSIOLOGICAL FACTORS INVOLVE ENDOCRINOLOGICAL CHANGES, SUCH AS INCREASED GLUCOCORTICOIDS, PROLACTIN, LEPTIN AND PARATHYROID HORMONE LEVELS AND REDUCED GONADAL HORMONES. LOW-GRADE INFLAMMATION AND HYPERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM DURING PSYCHOLOGICAL STRESS ARE ALSO PHYSIOLOGICAL CHANGES DETRIMENTAL TO BONE HEALTH. THE BEHAVIOURAL CHANGES DURING MENTAL STRESS, SUCH AS ALTERED DIETARY PATTERN, CIGARETTE SMOKING, ALCOHOLISM AND PHYSICAL INACTIVITY, ALSO THREATEN THE SKELETAL SYSTEM. PSYCHOLOGICAL STRESS MAY BE PARTLY RESPONSIBLE FOR EPIGENETIC REGULATION OF SKELETAL DEVELOPMENT. IT MAY ALSO MEDIATE THE RELATIONSHIP BETWEEN SOCIOECONOMIC STATUS AND BONE HEALTH. HOWEVER, MORE DIRECT EVIDENCE IS REQUIRED TO PROVE THESE HYPOTHESES. IN CONCLUSION, CHRONIC PSYCHOLOGICAL STRESS SHOULD BE RECOGNISED AS A RISK FACTOR OF OSTEOPOROSIS AND STRESS-COPING METHODS SHOULD BE INCORPORATED AS PART OF THE COMPREHENSIVE OSTEOPOROSIS-PREVENTING STRATEGY. 2021 14 6872 29 [POLYPHENOLS AS PROMISING BIOACTIVE COMPOUNDS]. POLYPHENOLS ARE DIVERSE AND WIDESPREAD BIOACTIVE PLANT-BASED COMPOUNDS. THESE COMPOUNDS ARE FOUND IN VARIOUS FOODS SUCH AS BERRIES, FRUITS, VEGETABLES, CEREALS, NUTS, COFFEE, CACAO, SPICES, SEEDS. THEY ARE DIVIDED INTO PHENOLIC ACIDS, STILBENES, FLAVONOIDS, LIGNANS DEPENDING ON THEIR MOLECULAR STRUCTURE. THEY ATTRACT THE ATTENTION OF RESEARCHERS DUE TO WIDE RANGE OF BIOLOGICAL EFFECTS ON HUMAN BODY. THE PURPOSE OF THIS WORK WAS TO ANALYZE MODERN SCIENTIFIC PUBLICATIONS ON THE BIOLOGICAL EFFECTS OF POLYPHENOLS. MATERIAL AND METHODS. THE REVIEW IS BASED ON PUBLICATIONS PRESENTED IN THE PUBMED, GOOGLE SCHOLAR, RESEARCHGATE, ELSEVIER, ELIBRARY, CYBERLENINKA DATABASES USING "POLYPHENOLS", "FLAVONOIDS", "RESVERATROL", "QUERCETIN", "CATECHINS" AS KEY WORDS. PREFERENCE WAS GIVEN TO ORIGINAL RESEARCHES OVER THE PAST 10 YEARS PUBLISHED IN REFEREED JOURNALS. RESULTS. OXIDATIVE STRESS, CHRONIC INFLAMMATION, MICROBIOME DISORDERS, INSULIN RESISTANCE, EXCESSIVE PROTEIN GLYCATION, AND GENOTOXIC EFFECTS ARE AT THE HEART OF THE PATHOGENESIS OF MANY DISEASES, INCLUDING THOSE ASSOCIATED WITH AGE. A LARGE AMOUNT OF MATERIAL HAS BEEN ACCUMULATED ON THE ANTIOXIDANT, ANTICARCINOGENIC, EPIGENETIC, METABOLIC, GEROPROTECTIVE, ANTI-INFLAMMATORY AND ANTIVIRAL EFFECTS OF POLYPHENOLS. THIS GIVES REASONS TO CONSIDER POLYPHENOLS AS VERY PROMISING MICRONUTRIENTS, WHICH INCLUSION IN THE DIET CAN REDUCE THE RISK OF DEVELOPING CARDIOVASCULAR, ONCOLOGICAL, NEURODEGENERATIVE DISEASES, DIABETES MELLITUS, OBESITY, METABOLIC SYNDROME, PREMATURE AGING, THAT IS, THE MAIN CAUSES OF DEATH, A DECREASE IN THE DURATION AND QUALITY OF LIFE OF A MODERN PERSON. CONCLUSION. EXPANDING THE RANGE OF PRODUCTS ENRICHED WITH POLYPHENOLS WITH THEIR HIGH BIOAVAILABILITY IS A PROMISING AREA OF SCIENTIFIC RESEARCH AND DEVELOPMENT OF PRODUCTION IN ORDER TO PREVENT SOCIALLY SIGNIFICANT AGE-ASSOCIATED DISEASES. 2023 15 1388 16 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE. 2021 16 285 20 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 17 4145 22 MECHANISMS OF VASCULAR AGING. AGING OF THE VASCULATURE PLAYS A CENTRAL ROLE IN MORBIDITY AND MORTALITY OF OLDER PEOPLE. TO DEVELOP NOVEL TREATMENTS FOR AMELIORATION OF UNSUCCESSFUL VASCULAR AGING AND PREVENTION OF AGE-RELATED VASCULAR PATHOLOGIES, IT IS ESSENTIAL TO UNDERSTAND THE CELLULAR AND FUNCTIONAL CHANGES THAT OCCUR IN THE VASCULATURE DURING AGING. IN THIS REVIEW, THE PATHOPHYSIOLOGICAL ROLES OF FUNDAMENTAL CELLULAR AND MOLECULAR MECHANISMS OF AGING, INCLUDING OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, IMPAIRED RESISTANCE TO MOLECULAR STRESSORS, CHRONIC LOW-GRADE INFLAMMATION, GENOMIC INSTABILITY, CELLULAR SENESCENCE, EPIGENETIC ALTERATIONS, LOSS OF PROTEIN HOMEOSTASIS, DEREGULATED NUTRIENT SENSING, AND STEM CELL DYSFUNCTION IN THE VASCULAR SYSTEM ARE CONSIDERED IN TERMS OF THEIR CONTRIBUTION TO THE PATHOGENESIS OF BOTH MICROVASCULAR AND MACROVASCULAR DISEASES ASSOCIATED WITH OLD AGE. THE IMPORTANCE OF PROGERONIC AND ANTIGERONIC CIRCULATING FACTORS IN RELATION TO DEVELOPMENT OF VASCULAR AGING PHENOTYPES ARE DISCUSSED. FINALLY, FUTURE DIRECTIONS AND OPPORTUNITIES TO DEVELOP NOVEL INTERVENTIONS TO PREVENT/DELAY AGE-RELATED VASCULAR PATHOLOGIES BY TARGETING FUNDAMENTAL CELLULAR AND MOLECULAR AGING PROCESSES ARE PRESENTED. 2018 18 4467 20 MOLECULAR MECHANISMS OF VASCULAR HEALTH: INSIGHTS FROM VASCULAR AGING AND CALCIFICATION. CARDIOVASCULAR DISEASE IS THE MOST COMMON CAUSE OF DEATH WORLDWIDE, ESPECIALLY BEYOND THE AGE OF 65 YEARS, WITH THE VAST MAJORITY OF MORBIDITY AND MORTALITY DUE TO MYOCARDIAL INFARCTION AND STROKE. VASCULAR PATHOLOGY STEMS FROM A COMBINATION OF GENETIC RISK, ENVIRONMENTAL FACTORS, AND THE BIOLOGIC CHANGES ASSOCIATED WITH AGING. THE PATHOGENESIS UNDERLYING THE DEVELOPMENT OF VASCULAR AGING, AND VASCULAR CALCIFICATION WITH AGING, IN PARTICULAR, IS STILL NOT FULLY UNDERSTOOD. ACCUMULATING DATA SUGGESTS THAT GENETIC RISK, LIKELY COMPOUNDED BY EPIGENETIC MODIFICATIONS, ENVIRONMENTAL FACTORS, INCLUDING DIABETES AND CHRONIC KIDNEY DISEASE, AND THE PLASTICITY OF VASCULAR SMOOTH MUSCLE CELLS TO ACQUIRE AN OSTEOGENIC PHENOTYPE ARE MAJOR DETERMINANTS OF AGE-ASSOCIATED VASCULAR CALCIFICATION. UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING GENETIC AND MODIFIABLE RISK FACTORS IN REGULATING AGE-ASSOCIATED VASCULAR PATHOLOGY MAY INSPIRE STRATEGIES TO PROMOTE HEALTHY VASCULAR AGING. THIS ARTICLE SUMMARIZES CURRENT KNOWLEDGE OF CONCEPTS AND MECHANISMS OF AGE-ASSOCIATED VASCULAR DISEASE, WITH AN EMPHASIS ON VASCULAR CALCIFICATION. 2023 19 2835 17 FOOD AS MEDICINE: TARGETING THE URAEMIC PHENOTYPE IN CHRONIC KIDNEY DISEASE. THE OBSERVATION THAT UNHEALTHY DIETS (THOSE THAT ARE LOW IN WHOLE GRAINS, FRUITS AND VEGETABLES, AND HIGH IN SUGAR, SALT, SATURATED FAT AND ULTRA-PROCESSED FOODS) ARE A MAJOR RISK FACTOR FOR POOR HEALTH OUTCOMES HAS BOOSTED INTEREST IN THE CONCEPT OF 'FOOD AS MEDICINE'. THIS CONCEPT IS ESPECIALLY RELEVANT TO METABOLIC DISEASES, SUCH AS CHRONIC KIDNEY DISEASE (CKD), IN WHICH DIETARY APPROACHES ARE ALREADY USED TO AMELIORATE METABOLIC AND NUTRITIONAL COMPLICATIONS. INCREASED AWARENESS THAT TOXIC URAEMIC METABOLITES ORIGINATE NOT ONLY FROM INTERMEDIARY METABOLISM BUT ALSO FROM GUT MICROBIAL METABOLISM, WHICH IS DIRECTLY INFLUENCED BY DIET, HAS FUELLED INTEREST IN THE POTENTIAL OF 'FOOD AS MEDICINE' APPROACHES IN CKD BEYOND THE CURRENT STRATEGIES OF PROTEIN, SODIUM AND PHOSPHATE RESTRICTION. BIOACTIVE NUTRIENTS CAN ALTER THE COMPOSITION AND METABOLISM OF THE MICROBIOTA, ACT AS MODULATORS OF TRANSCRIPTION FACTORS INVOLVED IN INFLAMMATION AND OXIDATIVE STRESS, MITIGATE MITOCHONDRIAL DYSFUNCTION, ACT AS SENOLYTICS AND IMPACT THE EPIGENOME BY ALTERING ONE-CARBON METABOLISM. AS GUT DYSBIOSIS, INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, PREMATURE AGEING AND EPIGENETIC CHANGES ARE COMMON FEATURES OF CKD, THESE FINDINGS SUGGEST THAT TAILORED, HEALTHY DIETS THAT INCLUDE BIOACTIVE NUTRIENTS AS PART OF THE FOODOME COULD POTENTIALLY BE USED TO PREVENT AND TREAT CKD AND ITS COMPLICATIONS. 2021 20 3922 24 LIPIDS AND THE HALLMARKS OF AGEING: FROM PATHOLOGY TO INTERVENTIONS. LIPIDS ARE CRITICAL STRUCTURAL AND FUNCTIONAL ARCHITECTS OF CELLULAR HOMEOSTASIS. CHANGE IN SYSTEMIC LIPID PROFILE IS A CLINICAL INDICATOR OF UNDERLYING METABOLIC PATHOLOGIES, AND EMERGING EVIDENCE IS NOW DEFINING NOVEL ROLES OF LIPIDS IN MODULATING ORGANISMAL AGEING. CHARACTERISTIC ALTERATIONS IN LIPID METABOLISM CORRELATE WITH AGE, AND IMPAIRED SYSTEMIC LIPID PROFILE CAN ALSO ACCELERATE THE DEVELOPMENT OF AGEING PHENOTYPE. THE PRESENT WORK PROVIDES A COMPREHENSIVE REVIEW OF THE EXTENT OF LIPIDS AS REGULATORS OF THE MODERN HALLMARKS OF AGEING VIZ., CELLULAR SENESCENCE, CHRONIC INFLAMMATION, GUT DYSBIOSIS, TELOMERE ATTRITION, GENOME INSTABILITY, PROTEOSTASIS AND AUTOPHAGY, EPIGENETIC ALTERATIONS, AND STEM CELLS DYSFUNCTIONS. CURRENT EVIDENCE ON THE MODULATION OF EACH OF THESE HALLMARKS HAS BEEN DISCUSSED WITH EMPHASIS ON INHERENT AGE-DEPENDENT DEFICIENCIES IN LIPID METABOLISM AS WELL AS EXOGENOUS LIPID CHANGES. THERE APPEARS TO BE SUFFICIENT EVIDENCE TO CONSIDER IMPAIRED LIPID METABOLISM AS KEY DRIVER OF THE AGEING PROCESS ALTHOUGH MUCH OF KNOWLEDGE IS YET FRAGMENTED. CONSIDERING DIETARY LIPIDS, THE TYPE AND QUANTITY OF LIPIDS IN THE DIET IS A SIGNIFICANT, BUT OFTEN OVERLOOKED DETERMINANT THAT GOVERNS THE EFFECTS OF LIPIDS ON AGEING. FURTHER RESEARCH USING INTEGRATIVE APPROACHES AMIDST THE KNOWN AGING HALLMARKS IS HIGHLY DESIRABLE FOR UNDERSTANDING THE THERAPEUTICS OF LIPIDS ASSOCIATED WITH AGEING. 2023