1 4799 113 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 2 929 27 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 3 5322 29 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 3181 19 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 5 3922 29 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 6 798 38 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 7 182 25 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 8 6258 41 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 9 6668 40 URGENT NEEDS OF CAREGIVING IN AGEING POPULATIONS WITH ALZHEIMER'S DISEASE AND OTHER CHRONIC CONDITIONS: SUPPORT OUR LOVED ONES. THE AGEING PROCESS BEGINS AT BIRTH. IT IS A LIFE-LONG PROCESS, AND ITS EXACT ORIGINS ARE STILL UNKNOWN. SEVERAL HYPOTHESES ATTEMPT TO DESCRIBE THE NORMAL AGEING PROCESS, INCLUDING HORMONAL IMBALANCE, FORMATION OF REACTIVE OXYGEN SPECIES, DNA METHYLATION & DNA DAMAGE ACCUMULATION, LOSS OF PROTEOSTASIS, EPIGENETIC ALTERATIONS, MITOCHONDRIAL DYSFUNCTION, SENESCENCE, INFLAMMATION, AND STEM CELL DEPLETION. WITH INCREASED LIFESPAN IN ELDERLY INDIVIDUALS, THE PREVALENCE OF AGE-RELATED DISEASES INCLUDING, CANCER, DIABETES, OBESITY, HYPERTENSION, ALZHEIMER'S, ALZHEIMER'S DISEASE AND RELATED DEMENTIAS, PARKINSON'S, AND OTHER MENTAL ILLNESSES ARE INCREASED. THESE INCREASED AGE-RELATED ILLNESSES, PUT TREMENDOUS PRESSURE & BURDEN ON CAREGIVERS, FAMILY MEMBERS, AND FRIENDS WHO ARE LIVING WITH PATIENTS WITH AGE-RELATED DISEASES. AS MEDICAL NEEDS EVOLVE, THE CAREGIVER IS EXPECTED TO EXPERIENCE AN INCREASE IN DUTIES AND CHALLENGES, WHICH MAY RESULT IN STRESS ON THEMSELVES, AND IMPACT THEIR OWN FAMILY LIFE. IN THE CURRENT ARTICLE, WE ASSESS THE BIOLOGICAL MECHANISMS OF AGEING AND ITS EFFECT ON BODY SYSTEMS, EXPLORING LIFESTYLE AND AGEING, WITH A SPECIFIC FOCUS ON AGE-RELATED DISORDERS. WE ALSO DISCUSSED THE HISTORY OF CAREGIVING AND SPECIFIC CHALLENGES FACED BY CAREGIVERS IN THE PRESENCE OF MULTIPLE COMORBIDITIES. WE ALSO ASSESSED INNOVATIVE APPROACHES TO FUNDING CAREGIVING, AND EFFORTS TO IMPROVE THE MEDICAL SYSTEM TO BETTER ORGANIZE CHRONIC CARE EFFORTS, WHILE IMPROVING THE SKILL AND EFFICIENCY OF BOTH INFORMAL AND FORMAL CAREGIVERS. WE ALSO DISCUSSED THE ROLE OF CAREGIVING IN END-OF-LIFE CARE. OUR CRITICAL ANALYSIS STRONGLY SUGGESTS THAT THERE IS AN URGENT NEED FOR CAREGIVING IN AGED POPULATIONS AND SUPPORT FROM LOCAL, STATE, AND FEDERAL AGENCIES. 2023 10 285 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 11 5919 28 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 12 5629 33 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 13 4425 40 MOLECULAR BASIS OF AGEING IN CHRONIC METABOLIC DISEASES. AIM: OVER THE LAST DECADES, THE SHIFT IN AGE DISTRIBUTION TOWARDS OLDER AGES AND THE PROGRESSIVE AGEING WHICH HAS OCCURRED IN MOST POPULATIONS HAVE BEEN PARALLELED BY A GLOBAL EPIDEMIC OF OBESITY AND ITS RELATED METABOLIC DISORDERS, PRIMARILY, TYPE 2 DIABETES (T2D). DYSFUNCTION OF THE ADIPOSE TISSUE (AT) IS WIDELY RECOGNIZED AS A SIGNIFICANT HALLMARK OF THE AGEING PROCESS THAT, IN TURN, RESULTS IN SYSTEMIC METABOLIC ALTERATIONS. THESE INCLUDE INSULIN RESISTANCE, ACCUMULATION OF ECTOPIC LIPIDS AND CHRONIC INFLAMMATION, WHICH ARE RESPONSIBLE FOR AN ELEVATED RISK OF OBESITY AND T2D ONSET ASSOCIATED TO AGEING. ON THE OTHER HAND, OBESITY AND T2D, THE PARADIGMS OF AT DYSFUNCTION, SHARE MANY PHYSIOLOGICAL CHARACTERISTICS WITH THE AGEING PROCESS, SUCH AS AN INCREASED BURDEN OF SENESCENT CELLS AND EPIGENETIC ALTERATIONS. THUS, THESE CHRONIC METABOLIC DISORDERS MAY REPRESENT A STATE OF ACCELERATED AGEING. MATERIALS AND METHODS: A MORE PRECISE EXPLANATION OF THE FUNDAMENTAL AGEING MECHANISMS THAT OCCUR IN AT AND A DEEPER UNDERSTANDING OF THEIR ROLE IN THE INTERPLAY BETWEEN ACCELERATED AGEING AND AT DYSFUNCTION CAN BE A FUNDAMENTAL LEAP TOWARDS NOVEL THERAPIES THAT ADDRESS THE CAUSES, NOT JUST THE SYMPTOMS, OF OBESITY AND T2D, UTILIZING STRATEGIES THAT TARGET EITHER SENESCENT CELLS OR DNA METHYLATION. RESULTS: IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE PATHWAYS THAT LEAD TO AT DYSFUNCTION IN THE CHRONOLOGICAL AGEING PROCESS AS WELL AS THE PATHOPHYSIOLOGY OF OBESITY AND T2D, EMPHASIZING THE CRITICAL ROLE OF CELLULAR SENESCENCE AND DNA METHYLATION. CONCLUSION: FINALLY, WE HIGHLIGHT THE NEED FOR FURTHER RESEARCH FOCUSED ON TARGETING THESE MECHANISMS. 2020 14 4122 32 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 15 6188 32 THE IMPACT OF INSOMNIA ON FRAILTY AND THE HALLMARKS OF AGING. THROUGHOUT THE COURSE OF LIFE, THERE ARE AGE-RELATED CHANGES IN SLEEP. DESPITE THESE NORMAL CHANGES, THERE IS A HIGH PERCENTAGE OF OLDER ADULTS THAT REPORT SLEEP DISSATISFACTION WITH A HIGH PERVASIVENESS OF CHRONIC INSOMNIA, THE MOST COMMON SLEEP DISORDER WORLDWIDE, WITH ITS PREVALENCE BEING EXPECTED TO CONTINUOUSLY INCREASE DUE TO THE GROWING RATES OF AGING AND OBESITY. THIS CAN HAVE DIFFERENT ADVERSE HEALTH OUTCOMES, ESPECIALLY BY PROMOTING BOTH PHYSICAL AND COGNITIVE DECLINE, WHICH ULTIMATELY MAY AGGRAVATE FRAILTY IN OLDER ADULTS. MOREOVER, AGE-RELATED FRAILTY AND SLEEP DYSFUNCTION MAY HAVE A COMMON MECHANISM RELATED TO THE HALLMARKS OF CELLULAR AGING. CELLULAR AGING WAS CATEGORIZED INTO NINE HALLMARKS, SUCH AS DNA DAMAGE, TELOMERE ATTRITION AND EPIGENETIC CHANGES. IN THE CONTEXT OF GERIATRIC AND CHRONIC INSOMNIA RESEARCH, THIS REVIEW AIMS AT DISCUSSING THE CURRENT EVIDENCE FROM BOTH ANIMAL MODELS AND HUMAN COHORTS ADDRESSING THE LINK BETWEEN CHRONIC INSOMNIA, THE HALLMARKS OF AGING AND THEIR IMPACT ON FRAILTY. MOREOVER, THE MOST RECENT RESEARCH ABOUT THE PUTATIVE EFFECT OF INSOMNIA THERAPEUTIC APPROACHES ON HALLMARKS OF AGING WILL BE ALSO HIGHLIGHTED. 2023 16 5632 34 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 17 284 27 AGEING WITH HIV: CHALLENGES AND BIOMARKERS. THE ANTIRETROVIRAL TREATMENT (ART) DEVELOPED TO CONTROL HIV INFECTION LED TO A REVOLUTION IN THE PROGNOSIS OF PEOPLE LIVING WITH HIV (PLWH). PLWH UNDERWENT FROM SUFFERING SEVERE DISEASE AND OFTEN FATAL COMPLICATIONS AT YOUNG AGES TO HAVING A CHRONIC CONDITION AND A LIFE EXPECTANCY CLOSE TO THE GENERAL POPULATION. NEVERTHELESS, CHRONIC AGE-RELATED DISEASES INCREASE AS PLWH AGE. THE HARMFUL EFFECT OF HIV INFECTION ON THE INDIVIDUAL'S IMMUNE SYSTEM ADDS TO ITS DETERIORATION DURING AGEING, EXACERBATING COMORBIDITIES. IN ADDITION, PLWH ARE MORE EXPOSED TO RISK FACTORS AFFECTING AGEING, SUCH AS COINFECTIONS OR HARMFUL LIFESTYLES. THE ART INITIATION REVERSES THE BIOLOGICAL AGEING PROCESS BUT ONLY PARTIALLY, AND ADDITIONALLY CAN HAVE SOME TOXICITIES THAT INFLUENCE AGEING. OBSERVATIONAL STUDIES SUGGEST PREMATURE AGEING IN PLWH. THEREFORE, THERE IS CONSIDERABLE INTEREST IN THE EARLY PREDICTION OF UNHEALTHY AGEING THROUGH VALIDATED BIOMARKERS, EASY TO IMPLEMENT IN HIV-CLINICAL SETTINGS. THE MOST PROMISING BIOMARKERS ARE SECOND-GENERATION EPIGENETIC CLOCKS AND INTEGRATIVE ALGORITHMS. 2022 18 28 30 A BIOMIMETIC NATURAL SCIENCES APPROACH TO UNDERSTANDING THE MECHANISMS OF AGEING IN BURDEN OF LIFESTYLE DISEASES. THE WORLDWIDE LANDSCAPE OF AN AGEING POPULATION AND AGE-RELATED DISEASE BRINGS WITH IT HUGE SOCIO-ECONOMIC AND PUBLIC HEALTHCARE CONCERNS ACROSS NATIONS. CORRESPONDINGLY, MONUMENTAL HUMAN AND FINANCIAL RESOURCES HAVE BEEN INVESTED IN BIOMEDICAL RESEARCH, WITH A MISSION TO DECODE THE MECHANISMS OF AGEING AND HOW THESE CONTRIBUTE TO AGE-RELATED DISEASE. MULTIPLE HALLMARKS OF AGEING HAVE BEEN IDENTIFIED THAT ARE COMMON ACROSS TAXA, HIGHLIGHTING THEIR FUNDAMENTAL IMPORTANCE. THESE INCLUDE DYSREGULATED MITOCHONDRIAL METABOLISM AND TELOMERES BIOLOGY, EPIGENETIC MODIFICATIONS, CELL-MATRIX INTERACTIONS, PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, STEM CELL EXHAUSTION, INFLAMMAGEING AND IMMUNO-SENESCENCE. WHILE OUR UNDERSTANDING OF THE MOLECULAR BASIS OF AGEING IS IMPROVING, IT REMAINS A COMPLEX AND MULTIFACTORIAL PROCESS THAT REMAINS TO BE FULLY UNDERSTOOD. A KEY ASPECT OF THE SHORTFALL IN OUR UNDERSTANDING OF THE AGEING PROCESS LIES IN TRANSLATING DATA FROM STANDARD ANIMAL MODELS TO HUMANS. CONSEQUENTLY, WE SUGGEST THAT A 'BIOMIMETIC' AND COMPARATIVE APPROACH, INTEGRATING KNOWLEDGE FROM SPECIES IN THE WILD, AS OPPOSED TO INBRED GENETICALLY HOMOGENOUS LABORATORY ANIMALS, CAN PROVIDE POWERFUL INSIGHTS INTO HUMAN AGEING PROCESSES. HERE WE DISCUSS SOME PARTICULARITIES AND COMPARATIVE PATTERNS AMONG SEVERAL SPECIES FROM THE ANIMAL KINGDOM, ENDOWED WITH LONGEVITY OR SHORT LIFESPANS AND UNIQUE METABOLIC PROFILES THAT COULD BE POTENTIALLY EXPLOITED TO THE UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES. BASED UPON LESSONS FROM NATURE, WE ALSO HIGHLIGHT SEVERAL AVENUES FOR RENEWED FOCUS IN THE PATHOPHYSIOLOGY OF AGEING AND AGE-RELATED DISEASE (I.E. DIET-MICROBIOME-HEALTH AXIS, OXIDATIVE PROTEIN DAMAGE, ADAPTIVE HOMOEOSTASIS AND PLANETARY HEALTH). WE PROPOSE THAT A BIOMIMETIC ALLIANCE WITH COLLABORATIVE RESEARCH FROM DIFFERENT DISCIPLINES CAN IMPROVE OUR UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES WITH LONG-TERM SUSTAINABLE UTILITY. 2021 19 4145 29 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 20 5945 25 TARGETING THE "HALLMARKS OF AGING" TO SLOW AGING AND TREAT AGE-RELATED DISEASE: FACT OR FICTION? AGING IS A MAJOR RISK FACTOR FOR A NUMBER OF CHRONIC DISEASES, INCLUDING NEURODEGENERATIVE AND CEREBROVASCULAR DISORDERS. AGING PROCESSES HAVE THEREFORE BEEN DISCUSSED AS POTENTIAL TARGETS FOR THE DEVELOPMENT OF NOVEL AND BROADLY EFFECTIVE PREVENTATIVES OR THERAPEUTICS FOR AGE-RELATED DISEASES, INCLUDING THOSE AFFECTING THE BRAIN. MECHANISMS THOUGHT TO CONTRIBUTE TO AGING HAVE BEEN SUMMARIZED UNDER THE TERM THE "HALLMARKS OF AGING" AND INCLUDE A LOSS OF PROTEOSTASIS, MITOCHONDRIAL DYSFUNCTION, ALTERED NUTRIENT SENSING, TELOMERE ATTRITION, GENOMIC INSTABILITY, CELLULAR SENESCENCE, STEM CELL EXHAUSTION, EPIGENETIC ALTERATIONS AND ALTERED INTERCELLULAR COMMUNICATION. WE HERE EXAMINE KEY CLAIMS ABOUT THE "HALLMARKS OF AGING". OUR ANALYSIS REVEALS IMPORTANT WEAKNESSES THAT PRECLUDE STRONG AND DEFINITIVE CONCLUSIONS CONCERNING A POSSIBLE ROLE OF THESE PROCESSES IN SHAPING ORGANISMAL AGING RATE. SIGNIFICANT AMBIGUITY ARISES FROM THE OVERRELIANCE ON LIFESPAN AS A PROXY MARKER FOR AGING, THE USE OF MODELS WITH UNCLEAR RELEVANCE FOR ORGANISMAL AGING, AND THE USE OF STUDY DESIGNS THAT DO NOT ALLOW TO PROPERLY ESTIMATE INTERVENTION EFFECTS ON AGING RATE. WE ALSO DISCUSS FUTURE RESEARCH DIRECTIONS THAT SHOULD BE TAKEN TO CLARIFY IF AND TO WHAT EXTENT PUTATIVE AGING REGULATORS DO IN FACT INTERACT WITH AGING. THESE INCLUDE MULTIDIMENSIONAL ANALYTICAL FRAMEWORKS AS WELL AS DESIGNS THAT FACILITATE THE PROPER ASSESSMENT OF INTERVENTION EFFECTS ON AGING RATE. 2023