1 1558 98 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 2 4425 44 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 3 1523 33 DNA METHYLATION CHANGES AND INFLAMMAGING IN AGING-ASSOCIATED DISEASES. AGING AS AN INEVITABLE PHENOMENON IS ASSOCIATED WITH PERVASIVE CHANGES IN PHYSIOLOGICAL FUNCTIONS. THERE IS A RELATIONSHIP BETWEEN AGING AND THE INCREASE OF SEVERAL CHRONIC DISEASES. MOST AGE-RELATED DISORDERS ARE ACCOMPANIED BY AN UNDERLYING CHRONIC INFLAMMATORY STATE, AS DEMONSTRATED BY LOCAL INFILTRATION OF INFLAMMATORY CELLS AND GREATER LEVELS OF PROINFLAMMATORY CYTOKINES IN THE BLOODSTREAM. WITHIN INFLAMMAGING, MANY EPIGENETIC EVENTS, ESPECIALLY DNA METHYLATION, CHANGE. DURING THE AGING PROCESS, DUE TO ABERRATIONS OF DNA METHYLATION, BIOLOGICAL PROCESSES ARE DISRUPTED, LEADING TO THE EMERGENCE OR PROGRESSION OF A VARIETY OF HUMAN DISEASES, INCLUDING CANCER, NEURODEGENERATIVE DISORDERS, CARDIOVASCULAR DISEASE AND DIABETES. THE FOCUS OF THIS REVIEW IS ON DNA METHYLATION, WHICH IS INVOLVED IN INFLAMMAGING-RELATED ACTIVITIES, AND HOW ITS DYSREGULATION LEADS TO HUMAN DISORDERS. 2022 4 3102 46 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 5 6109 36 THE EPIGENETIC AGING, OBESITY, AND LIFESTYLE. THE PREVALENCE OF OBESITY HAS DRAMATICALLY INCREASED WORLDWIDE OVER THE PAST DECADES. AGING-RELATED CHRONIC CONDITIONS, SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, ARE MORE PREVALENT IN INDIVIDUALS WITH OBESITY, THUS REDUCING THEIR LIFESPAN. EPIGENETIC CLOCKS, THE NEW METRICS OF BIOLOGICAL AGE BASED ON DNA METHYLATION PATTERNS, COULD BE CONSIDERED A REFLECTION OF THE STATE OF ONE'S HEALTH. SEVERAL ENVIRONMENTAL EXPOSURES AND LIFESTYLE FACTORS CAN INDUCE EPIGENETIC AGING ACCELERATIONS, INCLUDING OBESITY, THUS LEADING TO AN INCREASED RISK OF AGE-RELATED DISEASES. THE INSIGHT INTO THE COMPLEX LINK BETWEEN OBESITY AND AGING MIGHT HAVE SIGNIFICANT IMPLICATIONS FOR THE PROMOTION OF HEALTH AND THE MITIGATION OF FUTURE DISEASE RISK. THE PRESENT NARRATIVE REVIEW TAKES INTO ACCOUNT THE INTERACTION BETWEEN EPIGENETIC AGING AND OBESITY, SUGGESTING THAT EPIGENOME MAY BE AN INTRIGUING TARGET FOR AGE-RELATED PHYSIOLOGICAL CHANGES AND THAT ITS MODIFICATION COULD INFLUENCE AGING AND PROLONG A HEALTHY LIFESPAN. THEREFORE, WE HAVE FOCUSED ON DNA METHYLATION AGE AS A CLINICAL BIOMARKER, AS WELL AS ON THE POTENTIAL REVERSAL OF EPIGENETIC AGE USING A PERSONALIZED DIET- AND LIFESTYLE-BASED INTERVENTION. 2022 6 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 7 1112 38 COMMON PATHOGENETIC MECHANISMS UNDERLYING AGING AND TUMOR AND MEANS OF INTERVENTIONS. RECENTLY, THERE HAS BEEN AN INCREASE IN THE INCIDENCE OF MALIGNANT TUMORS AMONG THE OLDER POPULATION. MOREOVER, THERE IS AN ASSOCIATION BETWEEN AGING AND CANCER. DURING THE PROCESS OF SENESCENCE, THE HUMAN BODY SUFFERS FROM A SERIES OF IMBALANCES, WHICH HAVE BEEN SHOWN TO FURTHER ACCELERATE AGING, TRIGGER TUMORIGENESIS, AND FACILITATE CANCER PROGRESSION. THEREFORE, EXPLORING THE JUNCTIONS OF AGING AND CANCER AND SEARCHING FOR NOVEL METHODS TO RESTORE THE JUNCTIONS IS OF GREAT IMPORTANCE TO INTERVENE AGAINST AGING-RELATED CANCERS. IN THIS REVIEW, WE HAVE IDENTIFIED THE UNDERLYING PATHOGENETIC MECHANISMS OF AGING-RELATED CANCERS BY COMPARING ALTERATIONS IN THE HUMAN BODY CAUSED BY AGING AND THE FACTORS THAT TRIGGER CANCERS. WE FOUND THAT THE COMMON MECHANISMS OF AGING AND CANCER INCLUDE CELLULAR SENESCENCE, ALTERATIONS IN PROTEOSTASIS, MICROBIOTA DISORDERS (DECREASED PROBIOTICS AND INCREASED PERNICIOUS BACTERIA), PERSISTENT CHRONIC INFLAMMATION, EXTENSIVE IMMUNOSENESCENCE, INORDINATE ENERGY METABOLISM, ALTERED MATERIAL METABOLISM, ENDOCRINE DISORDERS, ALTERED GENETIC EXPRESSION, AND EPIGENETIC MODIFICATION. FURTHERMORE, WE HAVE PROPOSED THAT AGING AND CANCER HAVE COMMON MEANS OF INTERVENTION, INCLUDING NOVEL USES OF COMMON MEDICINE (METFORMIN, RESVERATROL, AND RAPAMYCIN), DIETARY RESTRICTION, AND ARTIFICIAL MICROBIOTA INTERVENTION OR SELECTIVELY REPLENISHING SCARCE METABOLITES. IN ADDITION, WE HAVE SUMMARIZED THE RESEARCH PROGRESS OF EACH INTERVENTION AND REVEALED THEIR BIDIRECTIONAL EFFECTS ON CANCER PROGRESSION TO COMPARE THEIR RELIABILITY AND FEASIBILITY. THEREFORE, THE STUDY FINDINGS PROVIDE VITAL INFORMATION FOR ADVANCED RESEARCH STUDIES ON AGE-RELATED CANCERS. HOWEVER, THERE IS A NEED FOR FURTHER OPTIMIZATION OF THE DESCRIBED METHODS AND MORE SUITABLE METHODS FOR COMPLICATED CLINICAL PRACTICES. IN CONCLUSION, TARGETING AGING MAY HAVE POTENTIAL THERAPEUTIC EFFECTS ON AGING-RELATED CANCERS. 2022 8 285 32 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 9 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 10 2855 42 FROM INFLAMMAGING TO HEALTHY AGING BY DIETARY LIFESTYLE CHOICES: IS EPIGENETICS THE KEY TO PERSONALIZED NUTRITION? THE PROGRESSIVELY OLDER POPULATION IN DEVELOPED COUNTRIES IS REFLECTED IN AN INCREASE IN THE NUMBER OF PEOPLE SUFFERING FROM AGE-RELATED CHRONIC INFLAMMATORY DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, HEART AND LUNG DISEASES, CANCER, OSTEOPOROSIS, ARTHRITIS, AND DEMENTIA. THE HETEROGENEITY IN BIOLOGICAL AGING, CHRONOLOGICAL AGE, AND AGING-ASSOCIATED DISORDERS IN HUMANS HAVE BEEN ASCRIBED TO DIFFERENT GENETIC AND ENVIRONMENTAL FACTORS (I.E., DIET, POLLUTION, STRESS) THAT ARE CLOSELY LINKED TO SOCIOECONOMIC FACTORS. THE COMMON DENOMINATOR OF THESE FACTORS IS THE INFLAMMATORY RESPONSE. CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION DURING PHYSIOLOGICAL AGING AND IMMUNOSENESCENCE ARE INTERTWINED IN THE PATHOGENESIS OF PREMATURE AGING ALSO DEFINED AS 'INFLAMMAGING.' THE LATTER HAS BEEN ASSOCIATED WITH FRAILTY, MORBIDITY, AND MORTALITY IN ELDERLY SUBJECTS. HOWEVER, IT IS UNKNOWN TO WHAT EXTENT INFLAMMAGING OR LONGEVITY IS CONTROLLED BY EPIGENETIC EVENTS IN EARLY LIFE. TODAY, HUMAN DIET IS BELIEVED TO HAVE A MAJOR INFLUENCE ON BOTH THE DEVELOPMENT AND PREVENTION OF AGE-RELATED DISEASES. MOST PLANT-DERIVED DIETARY PHYTOCHEMICALS AND MACRO- AND MICRONUTRIENTS MODULATE OXIDATIVE STRESS AND INFLAMMATORY SIGNALING AND REGULATE METABOLIC PATHWAYS AND BIOENERGETICS THAT CAN BE TRANSLATED INTO STABLE EPIGENETIC PATTERNS OF GENE EXPRESSION. THEREFORE, DIET INTERVENTIONS DESIGNED FOR HEALTHY AGING HAVE BECOME A HOT TOPIC IN NUTRITIONAL EPIGENOMIC RESEARCH. INCREASING EVIDENCE HAS REVEALED THAT COMPLEX INTERACTIONS BETWEEN FOOD COMPONENTS AND HISTONE MODIFICATIONS, DNA METHYLATION, NON-CODING RNA EXPRESSION, AND CHROMATIN REMODELING FACTORS INFLUENCE THE INFLAMMAGING PHENOTYPE AND AS SUCH MAY PROTECT OR PREDISPOSE AN INDIVIDUAL TO MANY AGE-RELATED DISEASES. REMARKABLY, HUMANS PRESENT A BROAD RANGE OF RESPONSES TO SIMILAR DIETARY CHALLENGES DUE TO BOTH GENETIC AND EPIGENETIC MODULATIONS OF THE EXPRESSION OF TARGET PROTEINS AND KEY GENES INVOLVED IN THE METABOLISM AND DISTRIBUTION OF THE DIETARY CONSTITUENTS. HERE, WE WILL SUMMARIZE THE EPIGENETIC ACTIONS OF DIETARY COMPONENTS, INCLUDING PHYTOCHEMICALS, AND MACRO- AND MICRONUTRIENTS AS WELL AS METABOLITES, THAT CAN ATTENUATE INFLAMMAGING. WE WILL DISCUSS THE CHALLENGES FACING PERSONALIZED NUTRITION TO TRANSLATE HIGHLY VARIABLE INTERINDIVIDUAL EPIGENETIC DIET RESPONSES TO POTENTIAL INDIVIDUAL HEALTH BENEFITS/RISKS RELATED TO AGING DISEASE. 2015 11 5765 30 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 12 6629 23 UNDERSTANDING THE HUMAN AGING PROTEOME USING EPIDEMIOLOGICAL MODELS. HUMAN AGING IS A COMPLEX MULTIFACTORIAL PROCESS ASSOCIATED WITH A DECLINE OF PHYSICAL AND COGNITIVE FUNCTION AND HIGH SUSCEPTIBILITY TO CHRONIC DISEASES, INFLUENCED BY GENETIC, EPIGENETIC, ENVIRONMENTAL, AND DEMOGRAPHIC FACTORS. THIS CHAPTER WILL PROVIDE AN OVERVIEW ON THE USE OF EPIDEMIOLOGICAL MODELS WITH PROTEOMICS DATA AS A METHOD THAT CAN BE USED TO IDENTIFY FACTORS THAT MODULATE THE AGING PROCESS IN HUMANS. THIS IS DEMONSTRATED WITH PROTEOMICS DATA FROM HUMAN PLASMA AND SKELETAL MUSCLE, WHERE THE COMBINATION WITH EPIDEMIOLOGICAL MODELS IDENTIFIED A SET OF MITOCHONDRIAL, SPLICEOSOME, AND SENESCENCE PROTEINS AS WELL AS THE ROLE OF ENERGETIC PATHWAYS SUCH AS GLYCOLYSIS, AND ELECTRON TRANSPORT PATHWAYS THAT REGULATE THE AGING PROCESS. 2022 13 4122 30 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 14 3679 25 INFLAMMATION IN AGING: CAUSE, EFFECT, OR BOTH? AGING IS A PROGRESSIVE DEGENERATIVE PROCESS TIGHTLY INTEGRATED WITH INFLAMMATION. CAUSE AND EFFECT ARE NOT CLEAR. A NUMBER OF THEORIES HAVE BEEN DEVELOPED THAT ATTEMPT TO DEFINE THE ROLE OF CHRONIC INFLAMMATION IN AGING: REDOX STRESS, MITOCHONDRIAL DAMAGE, IMMUNOSENESCENCE, ENDOCRINOSENESCENCE, EPIGENETIC MODIFICATIONS, AND AGE-RELATED DISEASES. HOWEVER, NO SINGLE THEORY EXPLAINS ALL ASPECTS OF AGING; INSTEAD, IT IS LIKELY THAT MULTIPLE PROCESSES CONTRIBUTE AND THAT ALL ARE INTERTWINED WITH INFLAMMATORY RESPONSES. HUMAN IMMUNODEFICIENCY VIRUS (HIV)-INFECTED PATIENTS UNDERGO A PREMATURE AGING PHENOMENON WHICH MAY PROVIDE CLUES TO BETTER ELUCIDATE THE NATURE OF INFLAMMATION IN AGING. ENVIRONMENTAL AND LIFESTYLE EFFECTORS OF INFLAMMATION MAY ALSO CONTRIBUTE TO MODULATION OF BOTH INFLAMMATION AND AGE-RELATED DYSFUNCTION. 2012 15 6187 30 THE IMPACT OF IMMUNOSENESCENCE ON PULMONARY DISEASE. THE GLOBAL POPULATION IS AGING WITH SIGNIFICANT GAINS IN LIFE EXPECTANCY PARTICULARLY IN THE DEVELOPED WORLD. CONSEQUENTLY, GREATER FOCUS ON UNDERSTANDING THE PROCESSES THAT UNDERLIE PHYSIOLOGICAL AGING HAS OCCURRED. KEY FACETS OF ADVANCING AGE INCLUDE GENOMIC INSTABILITY, TELOMERE SHORTENING, EPIGENETIC CHANGES, AND DECLINES IN IMMUNE FUNCTION TERMED IMMUNOSENESCENCE. IMMUNOSENESCENCE AND ITS ASSOCIATED CHRONIC LOW GRADE SYSTEMIC "INFLAMM-AGING" CONTRIBUTE TO THE DEVELOPMENT AND PROGRESSION OF PULMONARY DISEASE IN OLDER INDIVIDUALS. THESE PHYSIOLOGICAL PROCESSES PREDISPOSE TO PULMONARY INFECTION AND CONFER SPECIFIC AND UNIQUE CLINICAL PHENOTYPES OBSERVED IN CHRONIC RESPIRATORY DISEASE INCLUDING LATE-ONSET ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND PULMONARY FIBROSIS. EMERGING CONCEPTS OF THE GUT AND AIRWAY MICROBIOME FURTHER COMPLICATE THE INTERRELATIONSHIP BETWEEN HOST AND MICROORGANISM PARTICULARLY FROM AN IMMUNOLOGICAL PERSPECTIVE AND ESPECIALLY SO IN THE SETTING OF IMMUNOSENESCENCE. THIS REVIEW FOCUSES ON OUR CURRENT UNDERSTANDING OF THE AGING PROCESS, IMMUNOSENESCENCE, AND HOW IT CAN POTENTIALLY IMPACT ON VARIOUS PULMONARY DISEASES AND THE HUMAN MICROBIOME. 2015 16 3922 33 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 17 282 26 AGEING AND LOW-LEVEL CHRONIC INFLAMMATION: THE ROLE OF THE BIOLOGICAL CLOCK. AGEING IS A MULTIFACTORIAL PHYSIOLOGICAL MANIFESTATION THAT OCCURS INEXORABLY AND GRADUALLY IN ALL FORMS OF LIFE. THIS PROCESS IS LINKED TO THE DECAY OF HOMEOSTASIS DUE TO THE PROGRESSIVE DECREASE IN THE REPARATIVE AND REGENERATIVE CAPACITY OF TISSUES AND ORGANS, WITH REDUCED PHYSIOLOGICAL RESERVE IN RESPONSE TO STRESS. AGEING IS CLOSELY RELATED TO OXIDATIVE DAMAGE AND INVOLVES IMMUNOSENESCENCE AND TISSUE IMPAIRMENT OR METABOLIC IMBALANCES THAT TRIGGER INFLAMMATION AND INFLAMMASOME FORMATION. ONE OF THE MAIN AGEING-RELATED ALTERATIONS IS THE DYSREGULATION OF THE IMMUNE RESPONSE, WHICH RESULTS IN CHRONIC LOW-LEVEL, SYSTEMIC INFLAMMATION, TERMED "INFLAMMAGING". GENETIC AND EPIGENETIC CHANGES, AS WELL AS ENVIRONMENTAL FACTORS, PROMOTE AND/OR MODULATE THE MECHANISMS OF AGEING AT THE MOLECULAR, CELLULAR, ORGAN, AND SYSTEM LEVELS. MOST OF THESE MECHANISMS ARE CHARACTERIZED BY TIME-DEPENDENT PATTERNS OF VARIATION DRIVEN BY THE BIOLOGICAL CLOCK. IN THIS REVIEW, WE DESCRIBE THE INVOLVEMENT OF AGEING-RELATED PROCESSES WITH INFLAMMATION IN RELATION TO THE FUNCTIONING OF THE BIOLOGICAL CLOCK AND THE MECHANISMS OPERATING THIS INTRICATE INTERACTION. 2022 18 4145 27 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 19 6258 38 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 6034 33 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020