1 5322 86 PULMONARY DISEASES AND AGEING. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND IDIOPATHIC PULMONARY FIBROSIS ARE REGARDED AS A DISEASES OF ACCELERATED LUNG AGEING AND SHOW ALL OF THE HALLMARKS OF AGEING, INCLUDING TELOMERE SHORTENING, CELLULAR SENESCENCE, ACTIVATION OF PI3 KINASE-MTOR SIGNALING, IMPAIRED AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, STEM CELL EXHAUSTION, EPIGENETIC CHANGES, ABNORMAL MICRORNA PROFILES, IMMUNOSENESCENCE AND A LOW GRADE CHRONIC INFLAMMATION DUE TO SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE (SASP). MANY OF THESE AGEING MECHANISMS ARE DRIVEN BY EXOGENOUS AND ENDOGENOUS OXIDATIVE STRESS. THERE IS ALSO A REDUCTION IN ANTI-AGEING MOLECULES, SUCH AS SIRTUINS AND KLOTHO, WHICH FURTHER ACCELERATE THE AGEING PROCESS. UNDERSTANDING THESE MOLECULAR MECHANISMS HAS IDENTIFIED SEVERAL NOVEL THERAPEUTIC TARGETS AND SEVERAL DRUGS AND DIETARY INTERVENTIONS ARE NOW IN DEVELOPMENT TO TREAT CHRONIC LUNG DISEASE. 2019 2 5629 75 SENESCENCE IN COPD AND ITS COMORBIDITIES. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS REGARDED AS A DISEASE OF ACCELERATED LUNG AGING. THIS AFFLICTION SHOWS ALL OF THE HALLMARKS OF AGING, INCLUDING TELOMERE SHORTENING, CELLULAR SENESCENCE, ACTIVATION OF PI3 KINASE-MTOR SIGNALING, IMPAIRED AUTOPHAGY, MITOCHONDRIAL DYSFUNCTION, STEM CELL EXHAUSTION, EPIGENETIC CHANGES, ABNORMAL MICRORNA PROFILES, IMMUNOSENESCENCE, AND A LOW-GRADE CHRONIC INFLAMMATION (INFLAMMAGING). MANY OF THESE PATHWAYS ARE DRIVEN BY CHRONIC EXOGENOUS AND ENDOGENOUS OXIDATIVE STRESS. THERE IS ALSO A REDUCTION IN ANTIAGING MOLECULES, SUCH AS SIRTUINS AND KLOTHO, WHICH FURTHER ACCELERATE THE AGING PROCESS. COPD IS ASSOCIATED WITH SEVERAL COMORBIDITIES (MULTIMORBIDITY), SUCH AS CARDIOVASCULAR AND METABOLIC DISEASES, THAT SHARE THE SAME PATHWAYS OF ACCELERATED AGING. UNDERSTANDING THESE MECHANISMS HAS HELPED IDENTIFY SEVERAL NOVEL THERAPEUTIC TARGETS, AND SEVERAL DRUGS AND DIETARY INTERVENTIONS ARE NOW IN DEVELOPMENT TO TREAT MULTIMORBIDITY. 2017 3 4122 67 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 4 5916 31 TARGETING AGING PATHWAYS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS BECOME A GLOBAL EPIDEMIC AND IS THE THIRD LEADING CAUSE OF DEATH WORLDWIDE. COPD IS CHARACTERIZED BY CHRONIC AIRWAY INFLAMMATION, LOSS OF ALVEOLAR-CAPILLARY UNITS, AND PROGRESSIVE DECLINE IN LUNG FUNCTION. MAJOR RISK FACTORS FOR COPD ARE CIGARETTE SMOKING AND AGING. COPD-ASSOCIATED PATHOMECHANISMS INCLUDE MULTIPLE AGING PATHWAYS SUCH AS TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, ALTERED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELL SENESCENCE, STEM CELL EXHAUSTION AND CHRONIC INFLAMMATION. IN THIS REVIEW, WE WILL HIGHLIGHT THE CURRENT LITERATURE THAT FOCUSES ON THE ROLE OF AGE AND AGING-ASSOCIATED SIGNALING PATHWAYS AS WELL AS THEIR IMPACT ON CURRENT TREATMENT STRATEGIES IN THE PATHOGENESIS OF COPD. FURTHERMORE, WE WILL DISCUSS ESTABLISHED AND EXPERIMENTAL COPD TREATMENTS INCLUDING SENOLYTIC AND ANTI-AGING THERAPIES AND THEIR POTENTIAL USE AS NOVEL TREATMENT STRATEGIES IN COPD. 2020 5 290 31 AGING AND PULMONARY FIBROSIS. IDIOPATHIC PULMONARY FIBROSIS IS A CHRONIC, PROGRESSIVE, AND USUALLY FATAL LUNG DISORDER OF UNKNOWN ETIOLOGY. THE DISEASE LIKELY RESULTS FROM THE INTERACTION OF GENETIC SUSCEPTIBILITY ARCHITECTURE, ENVIRONMENTAL FACTORS SUCH AS SMOKING, AND AN ABNORMAL EPIGENETIC REPROGRAMMING THAT LEADS TO A COMPLEX PATHOGENESIS. IDIOPATHIC PULMONARY FIBROSIS OCCURS IN MIDDLE-AGED AND MAINLY ELDERLY ADULTS, AND IN THIS CONTEXT AGE HAS EMERGED AS ITS STRONGEST RISK FACTOR. HOWEVER, THE MECHANISMS LINKING IT TO AGING ARE UNCERTAIN. RECENTLY, NINE MOLECULAR AND CELLULAR HALLMARKS OF AGING HAVE BEEN PROPOSED: GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DEREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF THESE MOLECULAR MECHANISMS AND THEIR INVOLVEMENT IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS, WHILE EMPHASIZING THAT THE STUDIES ON THIS DISEASE ARE FEW AND THE FINDINGS ARE NOT DEFINITIVE. 2016 6 182 33 ACCELERATED LUNG AGING AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE PREVALENCE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INCREASES EXPONENTIALLY WITH AGING. ITS PATHOGENESIS, HOWEVER, IS NOT WELL KNOWN AND ASIDE FROM SMOKING CESSATION, THERE ARE NO DISEASE-MODIFYING TREATMENTS FOR THIS DISEASE. AREAS COVERED: COPD IS ASSOCIATED WITH ACCELERATING AGING AND AGING-RELATED DISEASES. IN THIS REVIEW, WE WILL DISCUSS THE HALLMARKS OF AGING INCLUDING GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATION, LOSS OF PROTEOSTASIS, MITOCHONDRIAL DYSFUNCTION, DEREGULATED NUTRIENT SENSING, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION, WHICH MAY BE INVOLVED IN COPD PATHOGENESIS. EXPERT COMMENTARY: COPD AND THE AGING PROCESS SHARE SIMILAR MOLECULAR AND CELLULAR CHANGES. AGING-RELATED MOLECULAR PATHWAYS MAY REPRESENT NOVEL THERAPEUTIC TARGETS AND BIOMARKERS FOR COPD. 2019 7 6880 30 [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 8 5632 27 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 9 971 28 CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND THE HALLMARKS OF AGING. AGING IS CHARACTERIZED BY PROGRESSIVE DETERIORATION OF PHYSIOLOGICAL INTEGRITY, DECLINE IN HOMEOSTASIS, AND DEGENERATION OF THE TISSUES THAT OCCURS AFTER THE REPRODUCTIVE PHASE OF LIFE IS COMPLETE, LEADING TO IMPAIRED FUNCTION. THIS DETERIORATION IS AN IMPORTANT RISK FACTOR FOR CHRONIC LUNG PATHOLOGIES SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). COPD IS A DISEASE THAT DEVELOPS GRADUALLY. EMPHYSEMATOUS CHANGES IN THE LUNG TAKE YEARS TO DEVELOP AFTER EXPOSURE TO CIGARETTE SMOKE; HENCE, THE VAST MAJORITY OF PATIENTS ARE ELDERLY. THERE HAS BEEN A DRAMATIC INCREASE IN THE LIFE EXPECTANCY OF THE GENERAL POPULATION, RESULTING IN AN INCREASED BURDEN OF CHRONIC LUNG DISEASES. THERE IS GROWING EVIDENCE THAT MOLECULAR MECHANISMS INVOLVED IN AGING MAY ALSO PLAY A ROLE IN COPD PATHOGENESIS. RECENTLY, THE NINE HALLMARKS OF AGING WERE IDENTIFIED. IN THIS ARTICLE, WE WILL REVIEW THE NINE HALLMARKS OF AGING AND HOW EACH HALLMARK CONTRIBUTES TO THE PATHOGENESIS OF COPD. 2018 10 1894 32 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 11 4953 39 PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INDUCED BY CIGARETTE SMOKE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON RESPIRATORY DISEASE THAT IS CHARACTERIZED BY FUNCTIONAL AND STRUCTURAL ALTERATIONS PRIMARILY CAUSED BY LONG-TERM INHALATION OF HARMFUL PARTICLES. CIGARETTE SMOKE (CS) INDUCES AIRWAY INFLAMMATION IN COPD, WHICH IS KNOWN TO PERSIST EVEN AFTER SMOKING CESSATION. THIS REVIEW DISCUSSES THE BASIC PATHOGENESIS OF COPD, WITH PARTICULAR FOCUS ON AN ENDOGENOUS PROTECTIVE MECHANISM AGAINST OXIDATIVE STRESS VIA NRF2, ALTERED IMMUNE RESPONSE OF THE AIRWAY INFLAMMATORY CELLS, EXAGGERATED CELLULAR SENESCENCE OF THE LUNG STRUCTURAL CELLS, AND CELL DEATH WITH EXPANDED INFLAMMATION. RECENTLY, CS-INDUCED MITOCHONDRIA AUTOPHAGY IS REPORTED TO INITIATE PROGRAMMED NECROSIS (NECROPTOSIS). NECROPTOSIS IS A NEW CONCEPT OF CELL DEATH WHICH IS DRIVEN BY A DEFINED MOLECULAR PATHWAY ALONG WITH EXAGGERATED INFLAMMATION. THIS NEW CELL DEATH MECHANISM IS OF IMPORTANCE DUE TO ITS ABILITY TO PRODUCE MORE INFLAMMATORY SUBSTANCES DURING THE PROCESS OF EPITHELIAL DEATH, CONTRIBUTING TO PERSISTENT AIRWAY INFLAMMATION THAT CANNOT BE EXPLAINED BY APOPTOSIS-DERIVED CELL DEATH. AUTOPHAGY IS AN AUTO-CELL COMPONENT DEGRADATION SYSTEM EXECUTED BY LYSOSOMES THAT CONTROLS PROTEIN AND ORGANELLE DEGRADATION FOR SUCCESSFUL HOMEOSTASIS. AS WELL AS IN THE PROCESS OF NECROPTOSIS, AUTOPHAGY IS ALSO OBSERVED DURING CELLULAR SENESCENCE. AGING OF THE LUNGS RESULTS IN THE ACQUISITION OF SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES (SASP) THAT ARE KNOWN TO SECRETE INFLAMMATORY CYTOKINES, CHEMOKINES, GROWTH FACTORS, AND MATRIX METALLOPROTEINASES RESULTING IN CHRONIC LOW-GRADE INFLAMMATION. IN FUTURE RESEARCH, WE INTEND TO HIGHLIGHT THE GENETIC AND EPIGENETIC APPROACHES THAT CAN FACILITATE THE UNDERSTANDING OF DISEASE SUSCEPTIBILITY. THE GOAL OF PRECISION MEDICINE IS TO ESTABLISH MORE ACCURATE DIAGNOSIS AND TREATMENT METHODS BASED ON THE PATIENT-SPECIFIC PATHOGENIC CHARACTERISTICS. THIS REVIEW PROVIDES INSIGHTS INTO CS-INDUCED COPD PATHOGENESIS, WHICH CONTRIBUTES TO A VERY COMPLEX DISEASE. INVESTIGATING THE MECHANISM OF DEVELOPING COPD, ALONG WITH THE AVAILABILITY OF THE PARTICULAR INHIBITORS, WILL LEAD TO NEW THERAPEUTIC APPROACHES IN COPD TREATMENT. 2019 12 4377 29 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 13 5801 25 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 14 5484 35 REVEALING THE PATHOGENIC AND AGING-RELATED MECHANISMS OF THE ENIGMATIC IDIOPATHIC PULMONARY FIBROSIS. AN INTEGRAL MODEL. A GROWING BODY OF EVIDENCE INDICATES THAT ABERRANT ACTIVATION OF ALVEOLAR EPITHELIAL CELLS AND FIBROBLASTS IN AN AGING LUNG PLAYS A CRITICAL ROLE IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS (IPF). HOWEVER, THE BIOPATHOLOGICAL PROCESSES LINKING AGING WITH IPF AND THE MECHANISMS RESPONSIBLE FOR THE ABNORMAL ACTIVATION OF EPITHELIAL CELLS AND FIBROBLASTS HAVE NOT BEEN ELUCIDATED. MANY OF THE HALLMARKS OF AGING (E.G., GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, MITOCHONDRIAL DYSFUNCTION, AND CELLULAR SENESCENCE) HAVE BEEN PROPOSED AS ESSENTIAL MECHANISMS FOR THE DEVELOPMENT OF IPF; HOWEVER, THESE DISTURBANCES ARE NOT RESTRICTED TO IPF AND ALSO OCCUR IN OTHER AGING-RELATED LUNG DISORDERS, PRIMARILY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THEREFORE, AN UNANSWERED QUESTION IS WHY A CURRENT/FORMER SMOKER OF ABOUT 60 YEARS OF AGE WITH SHORTER TELOMERES, ALVEOLAR EPITHELIAL SENESCENCE, EXCESSIVE OXIDATIVE STRESS, AND MITOCHONDRIAL DYSFUNCTION DEVELOPS IPF AND NOT COPD; IN OTHER WORDS, WHAT MAKES OLD LUNGS SPECIFICALLY SUSCEPTIBLE TO DEVELOP IPF? IN THIS PERSPECTIVE, WE PROPOSE AN INTEGRAL MODEL IN WHICH THE COMBINATION OF SOME GENE VARIANTS AND/OR GENE EXPRESSION IN THE AGING LUNG RESULTS IN THE LOSS OF EPITHELIAL INTEGRITY AND CONSEQUENTLY IN THE FAILURE OF THE ALVEOLI TO CORRECTLY RESPOND TO INJURY AND TO FACE THE STRESS ASSOCIATED WITH MECHANICAL STRETCH. AFTERWARD, A DISTINCTIVE EPIGENETIC "REPROGRAMMING" THAT AFFECTS BOTH EPITHELIAL CELLS AND FIBROBLASTS PROVOKES, AMONG OTHERS, THE RECAPITULATION OF DEVELOPMENTAL PATHWAYS AND THE ABERRANT ACTIVATION AND MISCOMMUNICATION BETWEEN BOTH CELL TYPES, RESULTING IN THE EXAGGERATED PRODUCTION AND ACCUMULATION OF EXTRACELLULAR MATRIX AND THE SUBSEQUENT DESTRUCTION OF THE LUNG ARCHITECTURE. 2014 15 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 16 5630 32 SENESCENCE IN PULMONARY FIBROSIS: BETWEEN AGING AND EXPOSURE. TO DATE, CHRONIC PULMONARY PATHOLOGIES REPRESENT THE THIRD LEADING CAUSE OF DEATH IN THE ELDERLY POPULATION. EVIDENCE-BASED PROJECTIONS SUGGEST THAT >65 (YEARS OLD) INDIVIDUALS WILL ACCOUNT FOR APPROXIMATELY A QUARTER OF THE WORLD POPULATION BEFORE THE TURN OF THE CENTURY. GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DEREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, AND ALTERED INTERCELLULAR COMMUNICATION, ARE DESCRIBED AS THE NINE "HALLMARKS" THAT GOVERN CELLULAR FITNESS. ANY DEVIATION FROM THE NORMAL PATTERN INITIATES A COMPLEX CASCADE OF EVENTS CULMINATING TO A DISEASE STATE. THIS BLUEPRINT, ORIGINALLY EMPLOYED TO DESCRIBE ABERRANT CHANGES IN CANCER CELLS, CAN BE ALSO USED TO DESCRIBE AGING AND FIBROSIS. PULMONARY FIBROSIS (PF) IS THE RESULT OF A PROGRESSIVE DECLINE IN INJURY RESOLUTION PROCESSES STEMMING FROM ENDOGENOUS (PHYSIOLOGICAL DECLINE OR SOMATIC MUTATIONS) OR EXOGENOUS STRESS. ENVIRONMENTAL, DIETARY OR OCCUPATIONAL EXPOSURE ACCELERATES THE PATHOGENESIS OF A SENESCENT PHENOTYPE BASED ON (1) WINDOW OF EXPOSURE; (2) DOSE, DURATION, RECURRENCE; AND (3) CELLS TYPE BEING TARGETED. AS THE LUNG AGES, THE THRESHOLD TO GENERATE AN IRREVERSIBLY SENESCENT PHENOTYPE IS LOWERED. HOWEVER, WE DO NOT HAVE SUFFICIENT KNOWLEDGE TO MAKE ACCURATE PREDICTIONS. IN THIS REVIEW, WE PROVIDE AN ASSESSMENT OF THE LITERATURE THAT INTERROGATES LUNG EPITHELIAL, MESENCHYMAL, AND IMMUNE SENESCENCE AT THE INTERSECTION OF AGING, ENVIRONMENTAL EXPOSURE AND PULMONARY FIBROSIS. 2020 17 285 31 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 18 797 27 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 19 6258 37 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 20 5471 31 RESPIRATORY MUSCLE SENESCENCE IN AGEING AND CHRONIC LUNG DISEASES. AGEING IS A PROGRESSIVE CONDITION THAT USUALLY LEADS TO THE LOSS OF PHYSIOLOGICAL PROPERTIES. THIS PROCESS IS ALSO PRESENT IN RESPIRATORY MUSCLES, WHICH ARE AFFECTED BY BOTH SENESCENT CHANGES OCCURRING IN THE WHOLE ORGANISM AND THOSE THAT ARE MORE SPECIFIC FOR MUSCLES. THE MECHANISMS OF THE LATTER CHANGES INCLUDE OXIDATIVE STRESS, DECREASE IN NEUROTROPHIC FACTORS AND DNA ABNORMALITIES. AGEING NORMALLY COEXISTS WITH COMORBIDITIES, INCLUDING RESPIRATORY DISEASES, WHICH FURTHER DETERIORATE THE STRUCTURE AND FUNCTION OF RESPIRATORY MUSCLES. IN THIS CONTEXT, CHANGES INTRINSIC TO AGEING BECOME ENHANCED BY MORE SPECIFIC FACTORS SUCH AS THE IMPAIRMENT IN LUNG MECHANICS AND GAS EXCHANGE, EXACERBATIONS AND HYPOXIA. HYPOXIA IN PARTICULAR HAS A DIRECT EFFECT ON MUSCLES, MAINLY THROUGH THE EXPRESSION OF INDUCIBLE FACTORS (HYPOXIC-INDUCIBLE FACTOR), AND CAN RESULT IN OXIDATIVE STRESS AND CHANGES IN DNA, DECREASE IN MITOCHONDRIAL BIOGENESIS AND DEFECTS IN THE TISSUE REPAIR MECHANISMS. INTENSE EXERCISE CAN ALSO CAUSE DAMAGE IN RESPIRATORY MUSCLES OF ELDERLY RESPIRATORY PATIENTS, BUT THIS CAN BE FOLLOWED BY TISSUE REPAIR AND REMODELLING. HOWEVER, AGEING INTERFERES WITH MUSCLE REPAIR BY TAMPERING WITH THE FUNCTION OF SATELLITE CELLS, MAINLY DUE TO OXIDATIVE STRESS, DNA DAMAGE AND EPIGENETIC MECHANISMS. IN ADDITION TO THE NORMAL PROCESS OF AGEING, STRESS-INDUCED PREMATURE SENESCENCE CAN ALSO OCCUR, INVOLVING CHANGES IN THE EXPRESSION OF MULTIPLE GENES BUT WITHOUT MODIFICATIONS IN TELOMERE LENGTH. 2020