1 5432 79 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 2 4145 31 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 3 797 30 CELLULAR SENESCENCE IN OSTEOARTHRITIS PATHOLOGY. CELLULAR SENESCENCE IS A STATE OF STABLE PROLIFERATION ARREST OF CELLS. THE SENESCENCE PATHWAY HAS MANY BENEFICIAL EFFECTS AND IS SEEN TO BE ACTIVATED IN DAMAGED/STRESSED CELLS, AS WELL AS DURING EMBRYONIC DEVELOPMENT AND WOUND HEALING. HOWEVER, THE PERSISTENCE AND ACCUMULATION OF SENESCENT CELLS IN VARIOUS TISSUES CAN ALSO IMPAIR FUNCTION AND HAVE BEEN IMPLICATED IN THE PATHOGENESIS OF MANY AGE-RELATED DISEASES. OSTEOARTHRITIS (OA), A SEVERELY DEBILITATING CHRONIC CONDITION CHARACTERIZED BY PROGRESSIVE TISSUE REMODELING AND LOSS OF JOINT FUNCTION, IS THE MOST PREVALENT DISEASE OF THE SYNOVIAL JOINTS, AND INCREASING AGE IS THE PRIMARY OA RISK FACTOR. THE PROFILE OF INFLAMMATORY AND CATABOLIC MEDIATORS PRESENT DURING THE PATHOGENESIS OF OA IS STRIKINGLY SIMILAR TO THE SECRETORY PROFILE OBSERVED IN 'CLASSICAL' SENESCENT CELLS. DURING OA, CHONDROCYTES (THE SOLE CELL TYPE PRESENT WITHIN ARTICULAR CARTILAGE) EXHIBIT INCREASED LEVELS OF VARIOUS SENESCENCE MARKERS, SUCH AS SENESCENCE-ASSOCIATED BETA-GALACTOSIDASE (SABETAGAL) ACTIVITY, TELOMERE ATTRITION, AND ACCUMULATION OF P16INK4A. THIS SUGGESTS THE HYPOTHESIS THAT SENESCENCE OF CELLS WITHIN JOINT TISSUES MAY PLAY A PATHOLOGICAL ROLE IN THE CAUSATION OF OA. IN THIS REVIEW, WE DISCUSS THE MECHANISMS BY WHICH SENESCENT CELLS MAY PREDISPOSE SYNOVIAL JOINTS TO THE DEVELOPMENT AND/OR PROGRESSION OF OA, AS WELL AS TOUCHING UPON VARIOUS EPIGENETIC ALTERATIONS ASSOCIATED WITH BOTH OA AND SENESCENCE. 2017 4 4377 25 MITOCHONDRIAL AGING: FOCUS ON MITOCHONDRIAL DNA DAMAGE IN ATHEROSCLEROSIS - A MINI-REVIEW. ATHEROSCLEROSIS IS A COMPLEX DISEASE WHICH CAN BE DESCRIBED AS AN EXCESSIVE FIBROFATTY, PROLIFERATIVE, INFLAMMATORY RESPONSE TO DAMAGE TO THE ARTERY WALL INVOLVING SEVERAL CELL TYPES SUCH AS SMOOTH MUSCLE CELLS, MONOCYTE-DERIVED MACROPHAGES, LYMPHOCYTES, DENDRITIC CELLS AND PLATELETS. ON THE OTHER HAND, ATHEROSCLEROSIS IS A TYPICAL AGE-RELATED DEGENERATIVE PATHOLOGY, WHICH IS CHARACTERIZED BY SIGNS OF CELL SENESCENCE IN THE ARTERIAL WALL INCLUDING REDUCED CELL PROLIFERATION, IRREVERSIBLE GROWTH ARREST AND APOPTOSIS, INCREASED DNA DAMAGE, THE PRESENCE OF EPIGENETIC MODIFICATIONS, SHORTENING OF TELOMERE LENGTH AND MITOCHONDRIAL DYSFUNCTION. THE MOST PROMINENT CHARACTERISTICS OF MITOCHONDRIAL AGING ARE THEIR STRUCTURAL ALTERATIONS AND MITOCHONDRIAL DNA DAMAGE. THE MECHANISMS OF MITOCHONDRIAL GENOME DAMAGE IN THE DEVELOPMENT OF CHRONIC AGE-RELATED DISEASES SUCH AS ATHEROSCLEROSIS ARE NOT YET WELL UNDERSTOOD. THIS REVIEW FOCUSES ON THE LATEST FINDINGS FROM STUDIES OF THOSE MUTATIONS OF THE MITOCHONDRIAL GENOME WHICH MAY PLAY AN IMPORTANT ROLE IN THE DEVELOPMENT OF ATHEROSCLEROSIS AND WHICH ARE, AT THE SAME TIME, ALSO MARKERS OF MITOCHONDRIAL AGING AND CELL SENESCENCE. 2015 5 5632 29 SENESCENT CELLS: SASPECTED DRIVERS OF AGE-RELATED PATHOLOGIES. THE PROGRESSION OF PHYSIOLOGICAL AGEING IS DRIVEN BY INTRACELLULAR ABERRATIONS INCLUDING TELOMERE ATTRITION, GENOMIC INSTABILITY, EPIGENETIC ALTERATIONS AND LOSS OF PROTEOSTASIS. THESE IN TURN DAMAGE CELLS AND COMPROMISE THEIR FUNCTIONALITY. CELLULAR SENESCENCE, A STABLE IRREVERSIBLE CELL-CYCLE ARREST, IS ELICITED IN DAMAGED CELLS AND PREVENTS THEIR PROPAGATION IN THE ORGANISM. UNDER NORMAL CONDITIONS, SENESCENT CELLS RECRUIT THE IMMUNE SYSTEM WHICH FACILITATES THEIR REMOVAL FROM TISSUES. NEVERTHELESS, DURING AGEING, TISSUE-RESIDING SENESCENT CELLS TEND TO ACCUMULATE, AND MIGHT NEGATIVELY IMPACT THEIR MICROENVIRONMENT VIA PROFOUND SECRETORY PHENOTYPE WITH PRO-INFLAMMATORY CHARACTERISTICS, TERMED SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP). INDEED, SENESCENT CELLS ARE MOSTLY ABUNDANT AT SITES OF AGE-RELATED PATHOLOGIES, INCLUDING DEGENERATIVE DISORDERS AND MALIGNANCIES. INTERESTINGLY, STUDIES ON PROGEROID MICE INDICATE THAT SELECTIVE ELIMINATION OF SENESCENT CELLS CAN DELAY AGE-RELATED DETERIORATION. THIS SUGGESTS THAT CHRONIC INFLAMMATION INDUCED BY SENESCENT CELLS MIGHT BE A MAIN DRIVER OF THESE PATHOLOGIES. IMPORTANTLY, SENESCENT CELLS ACCUMULATE AS A RESULT OF DEFICIENT IMMUNE SURVEILLANCE, AND THEIR REMOVAL IS INCREASED UPON THE USE OF IMMUNE STIMULATORY AGENTS. INSIGHTS INTO MECHANISMS OF SENESCENCE SURVEILLANCE COULD BE COMBINED WITH CURRENT APPROACHES FOR CANCER IMMUNOTHERAPY TO PROPOSE NEW PREVENTIVE AND THERAPEUTIC STRATEGIES FOR AGE-RELATED DISEASES. 2014 6 6258 33 THE MOLECULAR MECHANISM OF POLYPHENOLS IN THE REGULATION OF AGEING HALLMARKS. AGEING IS A COMPLEX PROCESS CHARACTERIZED MAINLY BY A DECLINE IN THE FUNCTION OF CELLS, TISSUES, AND ORGANS, RESULTING IN AN INCREASED RISK OF MORTALITY. THIS PROCESS INVOLVES SEVERAL CHANGES, DESCRIBED AS HALLMARKS OF AGEING, WHICH INCLUDE GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL DEPLETION, AND ALTERED INTRACELLULAR COMMUNICATION. THE DETERMINING ROLE THAT ENVIRONMENTAL FACTORS SUCH AS DIET AND LIFESTYLE PLAY ON HEALTH, LIFE EXPECTANCY, AND SUSCEPTIBILITY TO DISEASES, INCLUDING CANCER AND NEURODEGENERATIVE DISEASES, IS WELLESTABLISHED. IN VIEW OF THE GROWING INTEREST IN THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN THE PREVENTION OF CHRONIC DISEASES, SEVERAL STUDIES HAVE BEEN CONDUCTED, AND THEY STRONGLY SUGGEST THAT THE INTAKE OF DIETARY POLYPHENOLS MAY BRING NUMEROUS BENEFITS DUE TO THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES, AND THEIR INTAKE HAS BEEN ASSOCIATED WITH IMPAIRED AGEING IN HUMANS. POLYPHENOL INTAKE HAS BEEN SHOWN TO BE EFFECTIVE IN AMELIORATING SEVERAL AGE-RELATED PHENOTYPES, INCLUDING OXIDATIVE STRESS, INFLAMMATORY PROCESSES, IMPAIRED PROTEOSTASIS, AND CELLULAR SENESCENCE, AMONG OTHER FEATURES, WHICH CONTRIBUTE TO AN INCREASED RISK OF AGEING-ASSOCIATED DISEASES. THIS REVIEW AIMS TO ADDRESS, IN A GENERAL WAY, THE MAIN FINDINGS DESCRIBED IN THE LITERATURE ABOUT THE BENEFITS OF POLYPHENOLS IN EACH OF THE HALLMARKS OF AGEING, AS WELL AS THE MAIN REGULATORY MECHANISMS RESPONSIBLE FOR THE OBSERVED ANTIAGEING EFFECTS. 2023 7 5801 20 STIFFNESS AND AGING IN CARDIOVASCULAR DISEASES: THE DANGEROUS RELATIONSHIP BETWEEN FORCE AND SENESCENCE. BIOLOGICAL AGING IS A PROCESS ASSOCIATED WITH A GRADUAL DECLINE IN TISSUES' HOMEOSTASIS BASED ON THE PROGRESSIVE INABILITY OF THE CELLS TO SELF-RENEW. CELLULAR SENESCENCE IS ONE OF THE HALLMARKS OF THE AGING PROCESS, CHARACTERIZED BY AN IRREVERSIBLE CELL CYCLE ARREST DUE TO REACTIVE OXYGEN SPECIES (ROS) PRODUCTION, TELOMERES SHORTENING, CHRONIC INFLAMMATORY ACTIVATION, AND CHROMATIN MODIFICATIONS. IN THIS REVIEW, WE WILL DESCRIBE THE EFFECTS OF SENESCENCE ON TISSUE STRUCTURE, EXTRACELLULAR MATRIX (ECM) ORGANIZATION, AND NUCLEUS ARCHITECTURE, AND SEE HOW THESE CHANGES AFFECT (ARE AFFECTED BY) MECHANO-TRANSDUCTION. IN OUR VIEW, THIS IS ESSENTIAL FOR A DEEPER UNDERSTANDING OF THE PROGRESSIVE PATHOLOGICAL EVOLUTION OF THE CARDIOVASCULAR SYSTEM AND ITS RELATIONSHIP WITH THE DETRIMENTAL EFFECTS OF RISK FACTORS, KNOWN TO ACT AT AN EPIGENETIC LEVEL. 2021 8 4037 19 MACROPHAGE IMMUNOMETABOLISM AND INFLAMMAGING: ROLES OF MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, CD38, AND NAD. AGING IS A COMPLEX PROCESS THAT INVOLVES DYSFUNCTION ON MULTIPLE LEVELS, ALL OF WHICH SEEM TO CONVERGE ON INFLAMMATION. MACROPHAGES ARE INTIMATELY INVOLVED IN INITIATING AND RESOLVING INFLAMMATION, AND THEIR DYSREGULATION WITH AGE IS A PRIMARY CONTRIBUTOR TO INFLAMMAGING-A STATE OF CHRONIC, LOW-GRADE INFLAMMATION THAT DEVELOPS DURING AGING. AMONG THE AGE-RELATED CHANGES THAT OCCUR TO MACROPHAGES ARE A HEIGHTENED STATE OF BASAL INFLAMMATION AND DIMINISHED OR HYPERACTIVE INFLAMMATORY RESPONSES, WHICH SEEM TO BE DRIVEN BY METABOLIC-DEPENDENT EPIGENETIC CHANGES. IN THIS REVIEW ARTICLE WE PROVIDE A BRIEF OVERVIEW OF MITOCHONDRIAL FUNCTIONS AND AGE-RELATED CHANGES THAT OCCUR TO MACROPHAGES, WITH AN EMPHASIS ON HOW THE INFLAMMAGING ENVIRONMENT, SENESCENCE, AND NAD DECLINE CAN AFFECT THEIR METABOLISM, PROMOTE DYSREGULATION, AND CONTRIBUTE TO INFLAMMAGING AND AGE-RELATED PATHOLOGIES. 2020 9 6880 28 [RESEARCH PROGRESS OF LUNG AGING IN CHRONIC RESPIRATORY DISEASES]. CELL AGING IS AN EXTREMELY COMPLEX PROCESS, WHICH IS CHARACTERIZED BY MITOCHONDRIAL STRUCTURAL DYSFUNCTION, TELOMERE SHORTENING, INFLAMMATORY MICROENVIRONMENT, PROTEIN HOMEOSTASIS IMBALANCE, EPIGENETIC CHANGES, ABNORMAL DNA DAMAGE AND REPAIR, ETC. AGING IS USUALLY ACCOMPANIED BY STRUCTURAL AND FUNCTIONAL DAMAGE OF TISSUES AND ORGANS WHICH FURTHER INDUCES THE OCCURRENCE AND DEVELOPMENT OF AGING-RELATED DISEASES. AGING INCLUDES PHYSIOLOGICAL AGING CAUSED BY INCREASED AGE AND PATHOLOGICAL AGING INDUCED BY A VARIETY OF FACTORS. NOTEWORTHY, AS A TARGET ORGAN DIRECTLY CONTACTING WITH THE OUTSIDE AIR, LUNG IS MORE PRONE TO VARIOUS STIMULI, CAUSING PATHOLOGICAL PREMATURE AGING WHICH IS LUNG AGING. STUDIES HAVE FOUND THAT THERE IS A CERTAIN PROPORTION OF SENESCENT CELLS IN THE LUNGS OF MOST CHRONIC RESPIRATORY DISEASES. HOWEVER, THE UNDERLYING MECHANISM BY WHICH THESE SENESCENT CELLS INDUCE LUNG SENESCENCE AND THEIR ROLE IN CHRONIC RESPIRATORY DISEASES IS STILL OBSCURE. THIS PAPER FOCUSES ON THE CAUSES AND CLASSIFICATION OF LUNG AGING, THE INTERNAL MECHANISM OF LUNG AGING INVOLVED IN CHRONIC RESPIRATORY DISEASES, AND THE APPLICATION OF ANTI-AGING TREATMENTS IN CHRONIC RESPIRATORY DISEASES. WE HOPE TO PROVIDE NEW RESEARCH IDEAS AND THEORETICAL BASIS FOR THE CLINICAL PREVENTION AND TREATMENT IN CHRONIC RESPIRATORY DISEASES. 2022 10 1027 23 CIRCULATING MIRNAS IN SUCCESSFUL AND UNSUCCESSFUL AGING. A MINI-REVIEW. AGING IS A MULTIFACTORIAL PROCESS THAT AFFECTS THE ORGANISMS AT GENETIC, MOLECULAR AND CELLULAR LEVELS. THIS PROCESS MODIFIES SEVERAL TISSUES WITH A NEGATIVE IMPACT ON CELLS PHYSIOLOGY, TISSUES AND ORGANS FUNCTIONALITY, ALTERING THEIR REGENERATION CAPACITY. THE CHRONIC LOW-GRADE INFLAMMATION TYPICAL OF AGING, DEFINED AS INFLAMMAGING, IS A COMMON BIOLOGICAL FACTOR RESPONSIBLE FOR THE DECLINE AND BEGINNING OF THE DISEASE IN AGE. A MURINE PARABIOSIS MODEL THAT COMBINES THE VASCULAR SYSTEM OF OLD AND YOUNG ANIMALS, SUGGESTS THAT SOLUBLE FACTORS RELEASED BY YOUNG INDIVIDUALS MAY IMPROVE THE REGENERATIVE POTENTIAL OF OLD TISSUE. THEREFORE, CIRCULATING FACTORS HAVE A KEY ROLE IN THE INDUCTION OF AGING PHENOTYPE. MOREOVER, LIFESTYLE CAN INFLUENCE THE PHYSIOLOGICAL STATUS OF MULTIPLE ORGANS, VIA EPIGENETIC MECHANISMS. RECENTLY, MICRORNAS ARE CONSIDERED POTENTIAL SENSORS OF AGING. 2019 11 798 28 CELLULAR SENESCENCE, SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE, AND CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS INCREASINGLY BEING ACCEPTED AS A TYPE OF RENAL AGEING. THE KIDNEY UNDERGOES AGE-RELATED ALTERATIONS IN BOTH STRUCTURE AND FUNCTION. TO DATE, A COMPREHENSIVE ANALYSIS OF CELLULAR SENESCENCE AND SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP) IN CKD IS LACKING. HENCE, THIS REVIEW MAINLY DISCUSSES THE RELATIONSHIP BETWEEN THE TWO PHENOMENA TO SHOW THE STRIKING SIMILARITIES BETWEEN SASP AND CKD-ASSOCIATED SECRETORY PHENOTYPE (CASP). IT HAS BEEN REPORTED THAT REPLICATIVE SENESCENCE, STRESS-INDUCED PREMATURE AGEING, AND EPIGENETIC ABNORMALITIES PARTICIPATE IN THE OCCURRENCE AND DEVELOPMENT OF CKD. GENOMIC DAMAGE AND EXTERNAL ENVIRONMENTAL STIMULI CAUSE INCREASED LEVELS OF OXIDATIVE STRESS AND A CHRONIC INFLAMMATORY STATE AS A RESULT OF IRREVERSIBLE CELL CYCLE ARREST AND LOW DOSES OF SASP. SIMILAR TO SASP, CASP FACTORS ACTIVATE TISSUE REPAIR BY MULTIPLE MECHANISMS. ONCE TISSUE REPAIR FAILS, THE ACCUMULATED SASP OR CASP SPECIES AGGRAVATE DNA DAMAGE RESPONSE (DDR) AND CAUSE THE SENESCENT CELLS TO SECRETE MORE SASP FACTORS, ACCELERATING THE PROCESS OF CELLULAR AGEING AND EVENTUALLY LEADING TO VARIOUS AGEING-RELATED CHANGES. IT IS CONCLUDED THAT CELLULAR SENESCENCE AND SASP PARTICIPATE IN THE PATHOLOGICAL PROCESS OF CKD, AND CORRESPONDINGLY CKD ACCELERATED THE PROGRESSION OF CELL SENESCENCE AND THE SECRETION OF SASP. THESE RESULTS WILL FACILITATE THE INTEGRATION OF THESE MECHANISMS INTO THE CARE AND MANAGEMENT OF CKD AND OTHER AGE-RELATED DISEASES. 2017 12 5932 23 TARGETING EPIGENETIC REGULATORS FOR INFLAMMATION: MECHANISMS AND INTERVENTION THERAPY. EMERGING EVIDENCE INDICATES THAT RESOLUTION OF INFLAMMATION IS A CRITICAL AND DYNAMIC ENDOGENOUS PROCESS FOR HOST TISSUES DEFENDING AGAINST EXTERNAL INVASIVE PATHOGENS OR INTERNAL TISSUE INJURY. IT HAS LONG BEEN KNOWN THAT AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATORY DISORDERS ARE CHARACTERIZED BY DYSREGULATED IMMUNE RESPONSES, LEADING TO EXCESSIVE AND UNCONTROL TISSUE INFLAMMATION. THE DYSREGULATION OF EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION, POSTTRANSLATIONAL MODIFICATIONS TO HISTONE PROTEINS, AND NONCODING RNA EXPRESSION HAS BEEN IMPLICATED IN A HOST OF INFLAMMATORY DISORDERS AND THE IMMUNE SYSTEM. THE INFLAMMATORY RESPONSE IS CONSIDERED AS A CRITICAL TRIGGER OF EPIGENETIC ALTERATIONS THAT IN TURN INTERCEDE INFLAMMATORY ACTIONS. THUS, UNDERSTANDING THE MOLECULAR MECHANISM THAT DICTATES THE OUTCOME OF TARGETING EPIGENETIC REGULATORS FOR INFLAMMATORY DISEASE IS REQUIRED FOR INFLAMMATION RESOLUTION. IN THIS ARTICLE, WE ELUCIDATE THE CRITICAL ROLE OF THE NUCLEAR FACTOR-KAPPAB SIGNALING PATHWAY, JAK/STAT SIGNALING PATHWAY, AND THE NLRP3 INFLAMMASOME IN CHRONIC INFLAMMATORY DISEASES. AND WE FORMULATE THE RELATIONSHIP BETWEEN INFLAMMATION, CORONAVIRUS DISEASE 2019, AND HUMAN CANCERS. ADDITIONALLY, WE REVIEW THE MECHANISM OF EPIGENETIC MODIFICATIONS INVOLVED IN INFLAMMATION AND INNATE IMMUNE CELLS. ALL THAT MATTERS IS THAT WE PROPOSE AND DISCUSS THE REJUVENATION POTENTIAL OF INTERVENTIONS THAT TARGET EPIGENETIC REGULATORS AND REGULATORY MECHANISMS FOR CHRONIC INFLAMMATION-ASSOCIATED DISEASES TO IMPROVE THERAPEUTIC OUTCOMES. 2022 13 115 24 A STEM CELL AGING FRAMEWORK, FROM MECHANISMS TO INTERVENTIONS. STEM CELLS PLAY CENTRAL ROLES IN TISSUE DEVELOPMENT, HOMEOSTASIS, AND REGENERATION. DECADES OF SCIENTIFIC RESEARCH HAVE UNCOVERED PROCESSES OF STEM CELL DECLINE IN TISSUE AND ORGANISMAL AGING, AND MORE RECENTLY, PIONEERING TECHNOLOGIES PERMIT THE DISSECTION OF ITS UNDERLYING MECHANISMS AND INFORM THERAPEUTIC DEVELOPMENT FOR AGING AND AGING-ASSOCIATED DISORDERS. IN THIS REVIEW, WE ELUCIDATE AGING-RELATED FEATURES ACROSS DIFFERENT SOMATIC STEM CELL TYPES, WITH A SPECIFIC FOCUS ON EPIGENETIC CHANGES, LOSS OF PROTEIN HOMEOSTASIS, AND SYSTEMIC INFLUENCING FACTORS, INCLUDING CHRONIC INFLAMMATION, CIRCADIAN RHYTHM DYSREGULATION, AND METABOLIC DISORDER. OUR SURVEY OF ORGANISMAL STEM CELL AGING SUMMARIZES ITS UNDERLYING BIOLOGICAL IMPLICATIONS, POINTS TO POTENTIAL BIOMARKERS OF STEM CELL AGING, AND DISCUSSES STEM CELL-BASED THERAPEUTIC STRATEGIES WITH THE POTENTIAL FOR PROMOTING HEALTHY AGING AND COMBATING AGING AND AGE-RELATED DISEASES. 2022 14 278 21 AGE-RELATED INFLAMMATION: THE CONTRIBUTION OF DIFFERENT ORGANS, TISSUES AND SYSTEMS. HOW TO FACE IT FOR THERAPEUTIC APPROACHES. A TYPICAL FEATURE OF AGEING IS A CHRONIC, LOW-GRADE INFLAMMATION CHARACTERIZED BY A GENERAL INCREASE IN THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND INFLAMMATORY MARKERS ("INFLAMM-AGEING"). THIS STATUS MAY SLOWLY DAMAGE ONE OR SEVERAL ORGANS, ESPECIALLY WHEN UNFAVORABLE GENETIC POLYMORPHISMS AND EPIGENETIC ALTERATIONS ARE CONCOMITANT, LEADING TO AN INCREASED RISK OF FRAILTY TOGETHER WITH THE ONSET OF AGE-RELATED CHRONIC DISEASES. THE CONTRIBUTION OF DIFFERENT TISSUES (ADIPOSE TISSUE, MUSCLE), ORGANS (BRAIN, LIVER), IMMUNE SYSTEM AND ECOSYSTEMS (GUT MICROBIOTA) TO AGE-RELATED INFLAMMATION ("INFLAMM-AGEING") WILL BE DISCUSSED IN THIS REVIEW IN THE CONTEXT OF ITS ONSET/PROGRESSION LEADING TO SITE-RESTRICTED AND SYSTEMIC EFFECTS. MOREOVER, SOME OF THE POSSIBLE STRATEGIES AND THERAPIES TO COUNTERACT THE DIFFERENT SOURCES OF MOLECULAR MEDIATORS WHICH LEAD TO THE AGE-RELATED INFLAMMATORY PHENOTYPE WILL BE PRESENTED. 2010 15 285 25 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 16 5765 22 SOURCE OF CHRONIC INFLAMMATION IN AGING. AGING IS A COMPLEX PROCESS THAT RESULTS FROM A COMBINATION OF ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS. A CHRONIC PRO-INFLAMMATORY STATUS IS A PERVASIVE FEATURE OF AGING. THIS CHRONIC LOW-GRADE INFLAMMATION OCCURRING IN THE ABSENCE OF OVERT INFECTION HAS BEEN DEFINED AS "INFLAMMAGING" AND REPRESENTS A SIGNIFICANT RISK FACTOR FOR MORBIDITY AND MORTALITY IN THE ELDERLY. THE LOW-GRADE INFLAMMATION PERSISTS EVEN AFTER REVERSING PRO-INFLAMMATORY STIMULI SUCH AS LDL CHOLESTEROL AND THE RENIN-ANGIOTENSIN SYSTEM (RAS). RECENTLY, SEVERAL POSSIBLE SOURCES OF CHRONIC LOW-GRADE INFLAMMATION OBSERVED DURING AGING AND AGE-RELATED DISEASES HAVE BEEN PROPOSED. CELL SENESCENCE AND DYSREGULATION OF INNATE IMMUNITY IS ONE SUCH MECHANISM BY WHICH PERSISTENT PROLONGED INFLAMMATION OCCURS EVEN AFTER THE INITIAL STIMULUS HAS BEEN REMOVED. ADDITIONALLY, THE COAGULATION FACTOR THAT ACTIVATES INFLAMMATORY SIGNALING BEYOND ITS ROLE IN THE COAGULATION SYSTEM HAS BEEN IDENTIFIED. THIS SIGNAL COULD BE A NEW SOURCE OF CHRONIC INFLAMMATION AND CELL SENESCENCE. HERE, WE SUMMARIZED THE FACTORS AND CELLULAR PATHWAYS/PROCESSES THAT ARE KNOWN TO REGULATE LOW-GRADE PERSISTENT INFLAMMATION IN AGING AND AGE-RELATED DISEASE. 2018 17 1894 28 ENDOTHELIAL CELL SENESCENCE AND INFLAMMAGING: MICRORNAS AS BIOMARKERS AND INNOVATIVE THERAPEUTIC TOOLS. AGING IS ACCOMPANIED BY A PROGRESSIVE DECLINE OF ENDOTHELIAL FUNCTION AND A PROGRESSIVE DRIFT TOWARD A SYSTEMIC PRO-INFLAMMATORY STATUS THAT HAS BEEN DESIGNATED "INFLAMMAGING". BOTH PHENOMENA ARE ACCELERATED AND EXACERBATED IN PATIENTS WITH THE MOST COMMON AGE-RELATED DISEASES (ARDS), INCLUDING CANCER. THE FINDING THAT CHRONIC CELL STRESS ACTIVATES A PRO-INFLAMMATORY PROGRAM LEADING TO ACQUISITION OF THE SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP) AND TO THE PROPAGATION OF SENESCENCE TO SURROUNDING CELLS THROUGH THE SECRETOME, SUGGESTS THAT CELL SENESCENCE MAY HAVE A ROLE IN BOTH PROCESSES. HERE WE: I) DESCRIBE THE ROLE OF CELL SENESCENCE IN ENDOTHELIAL DYSFUNCTION, II) EMPHASIZE THE CONTRIBUTION OF THE ENDOTHELIAL CELL SASP TO INFLAMMAGING, AND III) SUGGEST THAT SELECTIVE REMOVAL OF SENESCENT ENDOTHELIAL CELLS MAY NOT ONLY HINDER SUCH HARMFUL PROCESSES, BUT ALSO REDUCE THE RISK OF DEVELOPING ARDS AND THEIR COMPLICATIONS. ALTHOUGH IN VIVO DETECTION AND TARGETING OF SENESCENT ENDOTHELIAL CELLS ARE STILL BEING INVESTIGATED, IT IS LIKELY THAT THERAPEUTIC STRATEGIES BASED ON ANTIOXIDANT AND ANTI-INFLAMMATORY COMPOUNDS WOULD INVOLVE GENERALIZED ANTI-AGING EFFECTS ALSO BENEFITING ENDOTHELIAL CELLS. MICRORNA (MIRNAS) - SINGLE-STRANDED, NON-CODING RNAS EXPRESSED BY ALL LIVING CELLS AND INVOLVED IN THE EPIGENETIC MODULATION OF ALL TRANSCRIPTIONAL PROGRAMS - MAY CONSTITUTE AN INNOVATIVE, VALUABLE TOOL TO DETECT AND TARGET SENESCENT ENDOTHELIAL CELLS AND TO DEVISE TREATMENTS THAT CAN SLOW DOWN THE PRO-INFLAMMATORY PROGRAM ACTIVATED IN SENESCENT ENDOTHELIAL CELLS. 2016 18 3102 30 GENOMIC INSTABILITIES, CELLULAR SENESCENCE, AND AGING: IN VITRO, IN VIVO AND AGING-LIKE HUMAN SYNDROMES. AS AVERAGE LIFE SPAN AND ELDERLY PEOPLE PREVALENCE IN THE WESTERN WORLD POPULATION IS GRADUALLY INCREASING, THE INCIDENCE OF AGE-RELATED DISEASES SUCH AS CANCER, HEART DISEASES, DIABETES, AND DEMENTIA IS INCREASING, BEARING SOCIAL AND ECONOMIC CONSEQUENCES WORLDWIDE. UNDERSTANDING THE MOLECULAR BASIS OF AGING-RELATED PROCESSES CAN HELP EXTEND THE ORGANISM'S HEALTH SPAN, I.E., THE LIFE PERIOD IN WHICH THE ORGANISM IS FREE OF CHRONIC DISEASES OR DECREASE IN BASIC BODY FUNCTIONS. DURING THE LAST FEW DECADES, IMMENSE PROGRESS WAS MADE IN THE UNDERSTANDING OF MAJOR COMPONENTS OF AGING AND HEALTHY AGING BIOLOGY, INCLUDING GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, PROTEOSTASIS, NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND INTRACELLULAR COMMUNICATIONS. THIS PROGRESS HAS BEEN MADE BY THREE SPEAR-HEADED STRATEGIES: IN VITRO (CELL AND TISSUE CULTURE FROM VARIOUS SOURCES), IN VIVO (INCLUDES DIVERSE MODEL AND NON-MODEL ORGANISMS), BOTH CAN BE MANIPULATED AND TRANSLATED TO HUMAN BIOLOGY, AND THE STUDY OF AGING-LIKE HUMAN SYNDROMES AND HUMAN POPULATIONS. HEREIN, WE WILL FOCUS ON CURRENT REPOSITORY OF GENOMIC "SENESCENCE" STAGE OF AGING, WHICH INCLUDES HEALTH DECLINE, STRUCTURAL CHANGES OF THE GENOME, FAULTY DNA DAMAGE RESPONSE AND DNA DAMAGE, TELOMERE SHORTENING, AND EPIGENETIC ALTERATIONS. ALTHOUGH AGING IS A COMPLEX PROCESS, MANY OF THE "HALLMARKS" OF AGING ARE DIRECTLY RELATED TO DNA STRUCTURE AND FUNCTION. THIS REVIEW WILL ILLUSTRATE THE VARIETY OF THESE STUDIES, DONE IN IN VITRO, IN VIVO AND HUMAN LEVELS, AND HIGHLIGHT THE UNIQUE POTENTIAL AND CONTRIBUTION OF EACH RESEARCH LEVEL AND EVENTUALLY THE LINK BETWEEN THEM. 2018 19 4122 22 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 20 3539 19 IMMUNE SENESCENCE, EPIGENETICS AND AUTOIMMUNITY. AGING OF THE IMMUNE SYSTEM IN HUMANS AND ANIMALS IS CHARACTERIZED BY A DECLINE IN BOTH ADAPTIVE AND INNATE IMMUNE RESPONSES. PARADOXICALLY, AGING IS ALSO ASSOCIATED WITH A STATE OF CHRONIC INFLAMMATION ("INFLAMMAGING") AND AN INCREASED LIKELIHOOD OF DEVELOPING AUTOIMMUNE DISEASES. EPIGENETIC CHANGES IN NON-DIVIDING AND DIVIDING CELLS, INCLUDING IMMUNE CELLS, DUE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO THE INFLAMMATION AND AUTOIMMUNITY THAT CHARACTERIZE BOTH THE STATE AND DISEASES OF AGING. HERE, WE REVIEW THE EPIGENETIC MECHANISMS INVOLVED IN THE DEVELOPMENT OF IMMUNE SENESCENCE AND AUTOIMMUNITY IN OLD AGE. 2018