1 3181 84 HALLMARKS OF AGING: AN EXPANDING UNIVERSE. AGING IS DRIVEN BY HALLMARKS FULFILLING THE FOLLOWING THREE PREMISES: (1) THEIR AGE-ASSOCIATED MANIFESTATION, (2) THE ACCELERATION OF AGING BY EXPERIMENTALLY ACCENTUATING THEM, AND (3) THE OPPORTUNITY TO DECELERATE, STOP, OR REVERSE AGING BY THERAPEUTIC INTERVENTIONS ON THEM. WE PROPOSE THE FOLLOWING TWELVE HALLMARKS OF AGING: GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, LOSS OF PROTEOSTASIS, DISABLED MACROAUTOPHAGY, DEREGULATED NUTRIENT-SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, ALTERED INTERCELLULAR COMMUNICATION, CHRONIC INFLAMMATION, AND DYSBIOSIS. THESE HALLMARKS ARE INTERCONNECTED AMONG EACH OTHER, AS WELL AS TO THE RECENTLY PROPOSED HALLMARKS OF HEALTH, WHICH INCLUDE ORGANIZATIONAL FEATURES OF SPATIAL COMPARTMENTALIZATION, MAINTENANCE OF HOMEOSTASIS, AND ADEQUATE RESPONSES TO STRESS. 2023 2 182 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 3 5322 27 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 4 5629 28 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 5 303 32 AIR POLLUTION STRESS AND THE AGING PHENOTYPE: THE TELOMERE CONNECTION. AGING IS A COMPLEX PHYSIOLOGICAL PHENOMENON. THE QUESTION WHY SOME SUBJECTS GROW OLD WHILE REMAINING FREE FROM DISEASE WHEREAS OTHERS PREMATURELY DIE REMAINS LARGELY UNANSWERED. WE FOCUS HERE ON THE ROLE OF AIR POLLUTION IN BIOLOGICAL AGING. HALLMARKS OF AGING CAN BE GROUPED INTO THREE MAIN CATEGORIES: GENOMIC INSTABILITY, TELOMERE ATTRITION, AND EPIGENETIC ALTERATIONS LEADING TO ALTERED MITOCHONDRIAL FUNCTION AND CELLULAR SENESCENCE. AT BIRTH, THE INITIAL TELOMERE LENGTH OF A PERSON IS LARGELY DETERMINED BY ENVIRONMENTAL FACTORS. TELOMERE LENGTH SHORTENS WITH EACH CELL DIVISION AND EXPOSURE TO AIR POLLUTION AS WELL AS LOW RESIDENTIAL GREENS SPACE EXPOSURE IS ASSOCIATED WITH SHORTER TELOMERE LENGTH. RECENT STUDIES SHOW THAT THE ESTIMATED EFFECTS OF PARTICULATE AIR POLLUTION EXPOSURE ON THE TELOMERE MITOCHONDRIAL AXIS OF AGING MAY PLAY AN IMPORTANT ROLE IN CHRONIC HEALTH EFFECTS OF AIR POLLUTION. THE EXPOSOME ENCOMPASSES ALL EXPOSURES OVER AN ENTIRE LIFE. AS TELOMERES CAN BE CONSIDERED AS THE CELLULAR MEMORIES OF EXPOSURE TO OXIDATIVE STRESS AND INFLAMMATION, TELOMERE MAINTENANCE MAY BE A PROXY FOR ASSESSING THE "EXPOSOME". IF TELOMERES ARE CAUSALLY RELATED TO THE AGING PHENOTYPE AND ENVIRONMENTAL AIR POLLUTION IS AN IMPORTANT DETERMINANT OF TELOMERE LENGTH, THIS MIGHT PROVIDE NEW AVENUES FOR FUTURE PREVENTIVE STRATEGIES. 2016 6 293 33 AGING HALLMARKS AND THE ROLE OF OXIDATIVE STRESS. AGING IS A COMPLEX BIOLOGICAL PROCESS ACCOMPANIED BY A PROGRESSIVE DECLINE IN THE PHYSICAL FUNCTION OF THE ORGANISM AND AN INCREASED RISK OF AGE-RELATED CHRONIC DISEASES SUCH AS CARDIOVASCULAR DISEASES, CANCER, AND NEURODEGENERATIVE DISEASES. STUDIES HAVE ESTABLISHED THAT THERE EXIST NINE HALLMARKS OF THE AGING PROCESS, INCLUDING (I) TELOMERE SHORTENING, (II) GENOMIC INSTABILITY, (III) EPIGENETIC MODIFICATIONS, (IV) MITOCHONDRIAL DYSFUNCTION, (V) LOSS OF PROTEOSTASIS, (VI) DYSREGULATED NUTRIENT SENSING, (VII) STEM CELL EXHAUSTION, (VIII) CELLULAR SENESCENCE, AND (IX) ALTERED CELLULAR COMMUNICATION. ALL THESE ALTERATIONS HAVE BEEN LINKED TO SUSTAINED SYSTEMIC INFLAMMATION, AND THESE MECHANISMS CONTRIBUTE TO THE AGING PROCESS IN TIMING NOT CLEARLY DETERMINED YET. NEVERTHELESS, MITOCHONDRIAL DYSFUNCTION IS ONE OF THE MOST IMPORTANT MECHANISMS CONTRIBUTING TO THE AGING PROCESS. MITOCHONDRIA IS THE PRIMARY ENDOGENOUS SOURCE OF REACTIVE OXYGEN SPECIES (ROS). DURING THE AGING PROCESS, THERE IS A DECLINE IN ATP PRODUCTION AND ELEVATED ROS PRODUCTION TOGETHER WITH A DECLINE IN THE ANTIOXIDANT DEFENSE. ELEVATED ROS LEVELS CAN CAUSE OXIDATIVE STRESS AND SEVERE DAMAGE TO THE CELL, ORGANELLE MEMBRANES, DNA, LIPIDS, AND PROTEINS. THIS DAMAGE CONTRIBUTES TO THE AGING PHENOTYPE. IN THIS REVIEW, WE SUMMARIZE RECENT ADVANCES IN THE MECHANISMS OF AGING WITH AN EMPHASIS ON MITOCHONDRIAL DYSFUNCTION AND ROS PRODUCTION. 2023 7 5919 36 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 8 3596 38 IMPLICATIONS OF SPHINGOLIPIDS ON AGING AND AGE-RELATED DISEASES. AGING IS A PROCESS LEADING TO A PROGRESSIVE LOSS OF PHYSIOLOGICAL INTEGRITY AND HOMEOSTASIS, AND A PRIMARY RISK FACTOR FOR MANY LATE-ONSET CHRONIC DISEASES. THE MECHANISMS UNDERLYING AGING HAVE LONG PIQUED THE CURIOSITY OF SCIENTISTS. HOWEVER, THE IDEA THAT AGING IS A BIOLOGICAL PROCESS SUSCEPTIBLE TO GENETIC MANIPULATION WAS NOT WELL ESTABLISHED UNTIL THE DISCOVERY THAT THE INHIBITION OF INSULIN/IGF-1 SIGNALING EXTENDED THE LIFESPAN OF C. ELEGANS. ALTHOUGH AGING IS A COMPLEX MULTISYSTEM PROCESS, LOPEZ-OTIN ET AL. DESCRIBED AGING IN REFERENCE TO NINE HALLMARKS OF AGING. THESE NINE 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. DUE TO RECENT ADVANCES IN LIPIDOMIC, INVESTIGATION INTO THE ROLE OF LIPIDS IN BIOLOGICAL AGING HAS INTENSIFIED, PARTICULARLY THE ROLE OF SPHINGOLIPIDS (SL). SLS ARE A DIVERSE GROUP OF LIPIDS ORIGINATING FROM THE ENDOPLASMIC RETICULUM (ER) AND CAN BE MODIFIED TO CREATE A VASTLY DIVERSE GROUP OF BIOACTIVE METABOLITES THAT REGULATE ALMOST EVERY MAJOR CELLULAR PROCESS, INCLUDING CELL CYCLE REGULATION, SENESCENCE, PROLIFERATION, AND APOPTOSIS. ALTHOUGH SL BIOLOGY REACHES ALL NINE HALLMARKS OF AGING, ITS CONTRIBUTION TO EACH HALLMARK IS DISPROPORTIONATE. IN THIS REVIEW, WE WILL DISCUSS IN DETAIL THE MAJOR CONTRIBUTIONS OF SLS TO THE HALLMARKS OF AGING AND AGE-RELATED DISEASES WHILE ALSO SUMMARIZING THE IMPORTANCE OF THEIR OTHER MINOR BUT INTEGRAL CONTRIBUTIONS. 2021 9 5956 21 TELOMERE AND TELOMERASE: BIOLOGICAL MARKERS OF ORGANIC VITAL FORCE STATE AND HOMEOPATHIC TREATMENT EFFECTIVENESS. BACKGROUND: PHILOSOPHICAL-SCIENTIFIC CORRELATIONS DESCRIBED IN PREVIOUS STUDIES SUGGEST THAT THE GENOME CAN BE THE BIOLOGICAL REPRESENTATION OF THE VITAL FORCE, WHILST THE DISEASE-PROMOTING EPIGENETIC ALTERATIONS WOULD BE THE BIOLOGICAL REPRESENTATION OF THE CHRONIC MIASMAS. IN THIS STUDY, WE EXPAND THE FUNCTIONAL CORRELATION BETWEEN VITAL FORCE AND CHROMOSOMES, DESCRIBING THE MECHANISM OF ACTION OF THE TELOMERE-TELOMERASE COMPLEX IN THE CONTEXT OF PHYSIOLOGICAL BALANCE. AIMS: THE AIM OF THE WORK IS TO STUDY THE ROLE OF THE TELOMERE-TELOMERASE COMPLEX IN CELL VITALITY, BIOLOGICAL AGING, AND THE HEALTH-DISEASE PROCESS, WITH THE GOAL OF PROPOSING THE USE OF TELOMERE LENGTH AS A BIOMARKER OF THE VITAL FORCE STATE AND THE EFFECTIVENESS OF HOMEOPATHIC TREATMENT. RESULTS: SIMILAR TO THE VITAL FORCE, TELOMERE LENGTH AND TELOMERASE ENZYME ACTIVITY PLAY AN IMPORTANT ROLE IN MAINTAINING CELLULAR VITALITY, BIOLOGICAL LONGEVITY, AND PHYSIOLOGICAL HOMEOSTASIS. TELOMERE SHORTENING FUNCTIONS AS A BIOMARKER OF VITAL IMBALANCE AND IS ASSOCIATED WITH NUMEROUS DISEASES AND HEALTH DISORDERS. ON THE OTHER HAND, HEALTH-PROMOTION PRACTICES NEUTRALIZE THE PATHOLOGICAL SHORTENING OF THE TELOMERES, ACTING THERAPEUTICALLY IN DISEASES OR AGE-DEPENDENT HEALTH DISORDERS. CONCLUSIONS: AS A HYPOTHETICAL BIOMARKER OF THE VITAL FORCE STATE, AN INTRA-INDIVIDUAL ANALYSIS OF THE MEAN LEUKOCYTE TELOMERE LENGTH BEFORE, DURING, AND AFTER HOMEOPATHIC TREATMENT CAN BE USED AS A BIOMARKER OF THERAPEUTIC EFFECTIVENESS. 2021 10 5959 19 TELOMERE LENGTH AS A MARKER OF BIOLOGICAL AGE: STATE-OF-THE-ART, OPEN ISSUES, AND FUTURE PERSPECTIVES. TELOMERE SHORTENING IS A WELL-KNOWN HALLMARK OF BOTH CELLULAR SENESCENCE AND ORGANISMAL AGING. AN ACCELERATED RATE OF TELOMERE ATTRITION IS ALSO A COMMON FEATURE OF AGE-RELATED DISEASES. THEREFORE, TELOMERE LENGTH (TL) HAS BEEN RECOGNIZED FOR A LONG TIME AS ONE OF THE BEST BIOMARKERS OF AGING. RECENT RESEARCH FINDINGS, HOWEVER, INDICATE THAT TL PER SE CAN ONLY ALLOW A ROUGH ESTIMATE OF AGING RATE AND CAN HARDLY BE REGARDED AS A CLINICALLY IMPORTANT RISK MARKER FOR AGE-RELATED PATHOLOGIES AND MORTALITY. EVIDENCE IS OBTAINED THAT OTHER INDICATORS SUCH AS CERTAIN IMMUNE PARAMETERS, INDICES OF EPIGENETIC AGE, ETC., COULD BE STRONGER PREDICTORS OF THE HEALTH STATUS AND THE RISK OF CHRONIC DISEASE. HOWEVER, DESPITE THESE ISSUES AND LIMITATIONS, TL REMAINS TO BE VERY INFORMATIVE MARKER IN ACCESSING THE BIOLOGICAL AGE WHEN USED ALONG WITH OTHER MARKERS SUCH AS INDICES OF HOMEOSTATIC DYSREGULATION, FRAILTY INDEX, EPIGENETIC CLOCK, ETC. THIS REVIEW ARTICLE IS AIMED AT DESCRIBING THE CURRENT STATE OF THE ART IN THE FIELD AND AT DISCUSSING RECENT RESEARCH FINDINGS AND DIVERGENT VIEWPOINTS REGARDING THE USEFULNESS OF LEUKOCYTE TL FOR ESTIMATING THE HUMAN BIOLOGICAL AGE. 2020 11 285 30 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 12 6189 25 THE IMPACT OF LIFE STRESS ON HALLMARKS OF AGING AND ACCELERATED SENESCENCE: CONNECTIONS IN SICKNESS AND IN HEALTH. CHRONIC STRESS IS A RISK FACTOR FOR NUMEROUS AGING-RELATED DISEASES AND HAS BEEN SHOWN TO SHORTEN LIFESPAN IN HUMANS AND OTHER SOCIAL MAMMALS. YET HOW LIFE STRESS CAUSES SUCH A VAST RANGE OF DISEASES IS STILL LARGELY UNCLEAR. IN RECENT YEARS, THE IMPACT OF STRESS ON HEALTH AND AGING HAS BEEN INCREASINGLY ASSOCIATED WITH THE DYSREGULATION OF THE SO-CALLED HALLMARKS OF AGING. THESE ARE BASIC BIOLOGICAL MECHANISMS THAT INFLUENCE INTRINSIC CELLULAR FUNCTIONS AND WHOSE ALTERATION CAN LEAD TO ACCELERATED AGING. HERE, WE REVIEW CORRELATIONAL AND EXPERIMENTAL LITERATURE (PRIMARILY FOCUSING ON EVIDENCE FROM HUMANS AND MURINE MODELS) ON THE CONTRIBUTION OF LIFE STRESS - PARTICULARLY STRESS DERIVED FROM ADVERSE SOCIAL ENVIRONMENTS - TO TRIGGER HALLMARKS OF AGING, INCLUDING CELLULAR SENESCENCE, STERILE INFLAMMATION, TELOMERE SHORTENING, PRODUCTION OF REACTIVE OXYGEN SPECIES, DNA DAMAGE, AND EPIGENETIC CHANGES. WE ALSO EVALUATE THE VALIDITY OF STRESS-INDUCED SENESCENCE AND ACCELERATED AGING AS AN ETIOPATHOLOGICAL PROPOSITION. FINALLY, WE HIGHLIGHT CURRENT GAPS OF KNOWLEDGE AND FUTURE DIRECTIONS FOR THE FIELD, AND DISCUSS PERSPECTIVES FOR TRANSLATIONAL GEROSCIENCE. 2023 13 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 14 4799 19 OBESITY AND AGEING: TWO SIDES OF THE SAME COIN. CONDITIONS AND COMORBIDITIES OF OBESITY MIRROR THOSE OF AGEING AND AGE-RELATED DISEASES. OBESITY AND AGEING SHARE A SIMILAR SPECTRUM OF PHENOTYPES SUCH AS COMPROMISED GENOMIC INTEGRITY, IMPAIRED MITOCHONDRIAL FUNCTION, ACCUMULATION OF INTRACELLULAR MACROMOLECULES, WEAKENED IMMUNITY, SHIFTS IN TISSUE AND BODY COMPOSITION, AND ENHANCED SYSTEMIC INFLAMMATION. MOREOVER, IT HAS BEEN SHOWN THAT OBESITY REDUCES LIFE EXPECTANCY BY 5.8 YEARS IN MEN AND 7.1 YEARS IN WOMEN AFTER THE AGE OF 40. SHORTER LIFE EXPECTANCY COULD BE BECAUSE OBESITY HOLISTICALLY ACCELERATES AGEING AT MULTIPLE LEVELS. BESIDES JEOPARDIZING NUCLEAR DNA AND MITOCHONDRIAL DNA INTEGRITY, OBESITY MODIFIES THE DNA METHYLATION PATTERN, WHICH IS ASSOCIATED WITH EPIGENETIC AGEING IN DIFFERENT TISSUES. ADDITIONALLY, OTHER SIGNS OF AGEING ARE SEEN IN INDIVIDUALS WITH OBESITY INCLUDING TELOMERE SHORTENING, SYSTEMIC INFLAMMATION, AND FUNCTIONAL DECLINES. THIS REVIEW AIMS TO SHOW HOW OBESITY AND AGEING ARE "TWO SIDES OF THE SAME COIN" THROUGH DISCUSSING HOW OBESITY PREDISPOSES AN INDIVIDUAL TO AGE-RELATED CONDITIONS, ILLNESS, AND DISEASE. WE WILL FURTHER DEMONSTRATE HOW THE MECHANISMS THAT PERPETUATE THE EARLY-ONSET OF CHRONIC DISEASES IN OBESITY PARALLEL THOSE OF AGEING. 2020 15 3102 37 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 16 929 20 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 17 798 21 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 18 1558 20 DNA METHYLATION MODULATES AGING PROCESS IN ADIPOCYTES. AGING HAS BEEN RECOGNIZED TO BE A HIGHLY COMPLEX BIOLOGICAL HEALTH PROBLEM WITH A HIGH RISK OF CHRONIC DISEASES, INCLUDING TYPE 2 DIABETES, ATHEROSCLEROSIS, CHRONIC BRONCHITIS OR EMPHYSEMA, CANCER AND ALZHEIMER'S DISEASE. PARTICULARLY, AGE-RELATED TURNOVER IN ADIPOSE TISSUE IS A MAJOR CONTRIBUTOR TO METABOLIC SYNDROMES AND SHORTENED LIFESPAN. ADIPOCYTES UNDERGO SENESCENCE IN EARLY STAGE, WHICH RESULTS IN ADIPOSE TISSUE METABOLIC DYSFUNCTION, REDISTRIBUTION, AND INFLAMMATION. THE WELL-ESTABLISHED ASSOCIATION BETWEEN DNA METHYLATION (DNAM) AND AGING HAS BEEN OBSERVED IN THE PAST FEW DECADES. INDEED, AGE-RELATED ALTERATION IN DNAM IS HIGHLY TISSUE-SPECIFIC. THIS REVIEW INTENDS TO SUMMARIZE THE ADVANCEMENTS HOW DNAM CHANGES COUPLED WITH AGING PROCESS IN ADIPOSE TISSUE, BY WHICH DNAM REGULATES CELLULAR SENESCENCE, METABOLIC FUNCTION, ADIPOKINE SECRETION AND BEIGING PROCESS IN ADIPOCYTES. ELUCIDATION OF THE EFFECT OF DNAM ON ADIPOSE AGING WOULD HAVE GREAT POTENTIAL TO THE DEVELOPMENT OF EPIGENETIC THERAPEUTIC STRATEGIES AGAINST AGING-RELATED DISEASES IN CLINICAL SETTINGS. 2022 19 6880 23 [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 20 4183 34 META-HALLMARKS OF AGING AND CANCER. BOTH AGING AND CANCER ARE CHARACTERIZED BY A SERIES OF PARTIALLY OVERLAPPING "HALLMARKS" THAT WE SUBJECT HERE TO A META-ANALYSIS. SEVERAL HALLMARKS OF AGING (I.E., GENOMIC INSTABILITY, EPIGENETIC ALTERATIONS, CHRONIC INFLAMMATION, AND DYSBIOSIS) ARE VERY SIMILAR TO SPECIFIC CANCER HALLMARKS AND HENCE CONSTITUTE COMMON "META-HALLMARKS," WHILE OTHER FEATURES OF AGING (I.E., TELOMERE ATTRITION AND STEM CELL EXHAUSTION) ACT LIKELY TO SUPPRESS ONCOGENESIS AND HENCE CAN BE VIEWED AS PREPONDERANTLY "ANTAGONISTIC HALLMARKS." DISABLED MACROAUTOPHAGY AND CELLULAR SENESCENCE ARE TWO HALLMARKS OF AGING THAT EXERT CONTEXT-DEPENDENT ONCOSUPPRESSIVE AND PRO-TUMORIGENIC EFFECTS. SIMILARLY, THE EQUIVALENCE OR ANTAGONISM BETWEEN AGING-ASSOCIATED DEREGULATED NUTRIENT-SENSING AND CANCER-RELEVANT ALTERATIONS OF CELLULAR METABOLISM IS COMPLEX. THE AGONISTIC AND ANTAGONISTIC RELATIONSHIP BETWEEN THE PROCESSES THAT DRIVE AGING AND CANCER HAS BEARINGS FOR THE AGE-RELATED INCREASE AND OLDEST AGE-RELATED DECREASE OF CANCER MORBIDITY AND MORTALITY, AS WELL AS FOR THE THERAPEUTIC MANAGEMENT OF MALIGNANT DISEASE IN THE ELDERLY. 2023