1 3577 133 IMPACT OF NUTRITION ON TELOMERE HEALTH: SYSTEMATIC REVIEW OF OBSERVATIONAL COHORT STUDIES AND RANDOMIZED CLINICAL TRIALS. DIET, PHYSICAL ACTIVITY, AND OTHER LIFESTYLE FACTORS HAVE BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF SEVERAL CHRONIC DISEASES, BUT ALSO IN A LOWER TOTAL MORTALITY AND LONGER LIFE EXPECTANCY. ONE OF THE MECHANISMS IN WHICH DIET CAN REDUCE THE RISK OF DISEASE IS WITH REGARD TO ITS IMPACT ON TELOMERES. TELOMERE LENGTH (TL) IS HIGHLY CORRELATED TO CHRONOLOGICAL AGE AND METABOLIC STATUS. INDIVIDUALS WITH SHORTER TELOMERES ARE AT HIGHER RISK OF CHRONIC DISEASES AND MORTALITY. DIET MAY INFLUENCE TL BY SEVERAL MECHANISMS SUCH AS REGULATING OXIDATIVE STRESS AND INFLAMMATION OR MODULATING EPIGENETIC REACTIONS. THE PRESENT SYSTEMATIC REVIEW AIMS TO EXAMINE THE RESULTS FROM EPIDEMIOLOGIC AND CLINICAL TRIALS CONDUCTED IN HUMANS EVALUATING THE ROLE OF NUTRIENTS, FOOD GROUPS, AND DIETARY PATTERNS ON TL. WE ALSO DISCUSS THE POSSIBLE MECHANISMS OF ACTION THAT INFLUENCE THIS PROCESS, WITH THE PERSPECTIVE THAT TL COULD BE A NOVEL BIOMARKER INDICATING THE RISK OF METABOLIC DISTURBANCES AND AGE-RELATED DISEASES. THE AVAILABLE EVIDENCE SUGGESTS THAT SOME ANTIOXIDANT NUTRIENTS, THE CONSUMPTION OF FRUITS AND VEGETABLES, AND MEDITERRANEAN DIET ARE MAINLY ASSOCIATED WITH LONGER TELOMERES. HOWEVER, MOST OF THE EVIDENCE IS BASED ON HIGH HETEROGENIC OBSERVATIONAL STUDIES AND VERY FEW RANDOMIZED CLINICAL TRIALS (RCTS). THEREFORE, THE ASSOCIATIONS SUMMARIZED IN THE PRESENT REVIEW NEED TO BE CONFIRMED WITH LARGER PROSPECTIVE COHORT STUDIES AND BETTER-DESIGNED RCTS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
2  625  37 BIOLOGICAL AGE AND ENVIRONMENTAL RISK FACTORS FOR DEMENTIA AND STROKE: MOLECULAR MECHANISMS. SINCE THE DEVELOPMENT OF ANTIBIOTICS AND VACCINATION, AS WELL AS MAJOR IMPROVEMENTS IN PUBLIC HYGIENE, THE MAIN RISK FACTORS FOR MORBIDITY AND MORTALITY ARE AGE AND CHRONIC EXPOSURE TO ENVIRONMENTAL FACTORS, BOTH OF WHICH CAN INTERACT WITH GENETIC PREDISPOSITIONS. AS THE AVERAGE AGE OF THE POPULATION INCREASES, THE PREVALENCE AND COSTS OF CHRONIC DISEASES, ESPECIALLY NEUROLOGICAL CONDITIONS, ARE RAPIDLY INCREASING. THE DELETERIOUS EFFECTS OF AGE AND ENVIRONMENTAL RISK FACTORS, DEVELOP CHRONICALLY OVER RELATIVELY LONG PERIODS OF TIME, IN CONTRAST TO THE RELATIVELY RAPID DELETERIOUS EFFECTS OF INFECTIOUS DISEASES OR ACCIDENTS. OF PARTICULAR INTEREST IS THE HYPOTHESIS THAT THE DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS MAY BE MEDIATED BY ACCELERATION OF BIOLOGICAL AGE. THIS HYPOTHESIS IS SUPPORTED BY EVIDENCE THAT DIETARY RESTRICTION, WHICH UNIVERSALLY DELAYS AGE-RELATED DISEASES, ALSO AMELIORATES DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS. CONVERSELY, BOTH AGE AND ENVIRONMENTAL RISK FACTORS ARE ASSOCIATED WITH THE ACCUMULATION OF SOMATIC MUTATIONS IN MITOTIC CELLS AND EPIGENETIC MODIFICATIONS THAT ARE A MEASURE OF "BIOLOGICAL AGE", A BETTER PREDICTOR OF AGE-RELATED MORBIDITY AND MORTALITY THAN CHRONOLOGICAL AGE. HERE WE REVIEW EVIDENCE THAT ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING AND AIR POLLUTION MAY ALSO DRIVE NEUROLOGICAL CONDITIONS, INCLUDING ALZHEIMER'S DISEASE, BY THE ACCELERATION OF BIOLOGICAL AGE, MEDIATED BY CUMULATIVE AND PERSISTENT EPIGENETIC EFFECTS AS WELL AS SOMATIC MUTATIONS. ELUCIDATION OF SUCH MECHANISMS COULD PLAUSIBLY ALLOW THE DEVELOPMENT OF INTERVENTIONS WHICH DELAY DELETERIOUS EFFECTS OF BOTH AGING AND ENVIRONMENTAL RISK FACTORS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
3 5959  42 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
4 6109  42 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
5 3676  41 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6 6346  35 THE ROLE OF EPIGENETICS IN CARDIOVASCULAR HEALTH AND AGEING: A FOCUS ON PHYSICAL ACTIVITY AND NUTRITION. THE CARDIOVASCULAR SYSTEM IS RESPONSIBLE FOR TRANSPORT OF BLOOD AND NUTRIENTS TO TISSUES, AND IS PIVOTAL TO THE PHYSIOLOGICAL HEALTH AND LONGEVITY. EPIGENETIC MODIFICATION IS A NATURAL, AGE-ASSOCIATED PROCESS RESULTING IN HIGHLY CONTEXTUALISED GENE EXPRESSION WITH CLEAR IMPLICATIONS FOR CELL DIFFERENTIATION AND DISEASE ONSET. BIOLOGICAL/EPIGENETIC AGE IS INDEPENDENT OF CHRONOLOGICAL AGE, CONSTITUTING A HIGHLY REFLECTIVE SNAPSHOT OF AN INDIVIDUAL'S OVERALL HEALTH. ACCELERATED VASCULAR AGEING IS OF MAJOR CONCERN, EFFECTIVELY LOWERING DISEASE THRESHOLD. AGE-RELATED CHRONIC ILLNESS INVOLVES A COMPLEX INTERPLAY BETWEEN MANY BIOLOGICAL PROCESSES AND IS MODULATED BY NON-MODIFIABLE AND MODIFIABLE RISK FACTORS. THESE ALTER THE STATIC GENOME BY A NUMBER OF EPIGENETIC MECHANISMS, WHICH CHANGE GENE EXPRESSION IN AN AGE AND LIFESTYLE DEPENDENT MANNER. THIS 'EPIGENETIC DRIFT' IMPACTS HEALTH AND CONTRIBUTES TO THE ETIOLOGY OF CHRONIC ILLNESS. LIFESTYLE FACTORS MAY CAUSE ACCELERATION OF THIS EPIGENETIC "CLOCK", PRE-DISPOSING INDIVIDUALS TO CARDIOVASCULAR DISEASE. NUTRITION AND PHYSICAL ACTIVITY ARE MODIFIABLE LIFESTYLE CHOICES, SYNERGISTICALLY CONTRIBUTING TO CARDIOVASCULAR HEALTH. THEY REPRESENT A POWERFUL POTENTIAL EPIGENETIC INTERVENTION POINT FOR EFFECTIVE CARDIOVASCULAR PROTECTIVE AND MANAGEMENT STRATEGIES. THUS, TOGETHER WITH TRADITIONAL RISK FACTORS, MONITORING THE EPIGENETIC SIGNATURE OF AGEING MAY PROVE BENEFICIAL FOR TAILORING LIFESTYLE TO FIT BIOLOGY - SUPPORTING THE INCREASINGLY POPULAR CONCEPT OF "AGEING WELL".	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
7 5183  38 PREMATURE AGING IN CHILDHOOD CANCER SURVIVORS. PROGRESS IN MEDICINE HAS INCREASED THE SURVIVAL TIME OF CHILDREN SUFFERING FROM CANCER; >80% OF PATIENTS SURVIVE FOR AT LEAST 5 YEARS FROM THE END OF TREATMENT. HOWEVER, THERE ARE LATE EFFECTS OF ANTICANCER THERAPY, WHICH ACCOMPANY THIS SUCCESS. TWO-THIRDS OF CHILDHOOD CANCER SURVIVORS (CCSS) HAVE AT LEAST ONE LATE EFFECT (ANY SIDE EFFECTS OR COMPLICATIONS OF ANTICANCER TREATMENT THAT APPEAR MONTHS TO YEARS AFTER THE COMPLETION OF TREATMENT), E.G. ENDOCRINOPATHIES, CARDIOVASCULAR DISEASES OR SUBSEQUENT CANCERS, AND HALF OF THESE LATE EFFECTS ARE SERIOUS OR LIFE THREATENING. THESE LATE CONSEQUENCES OF CHILDHOOD CANCER TREATMENT POSE A SERIOUS HEALTH, SOCIAL AND ECONOMIC PROBLEM. A COMMON MECHANISM FOR DEVELOPING A NUMBER OF LATE EFFECTS IS THE ONSET OF PREMATURE BIOLOGICAL AGING, WHICH IS ASSOCIATED WITH THE EARLY ONSET OF CHRONIC DISEASES AND DEATH. CELLULAR SENESCENCE IN CANCER SURVIVORS IS CAUSED BY THERAPY THAT CAN INDUCE CHROMOSOMAL ABERRATIONS, MUTATIONS, TELOMERE SHORTENING, EPIGENETIC ALTERATIONS AND MITOCHONDRIAL DYSFUNCTIONS. THE MECHANISMS OF ACCELERATED AGING IN CANCER SURVIVORS HAVE NOT YET BEEN FULLY CLARIFIED. THE MEASUREMENT OF BIOLOGICAL AGE IN SURVIVORS CAN HELP IMPROVE THE UNDERSTANDING OF AGING MECHANISMS AND IDENTIFY RISK FACTORS FOR PREMATURE AGING. HOWEVER, TO THE BEST OF OUR KNOWLEDGE, NO SINGLE MARKER FOR THE EVALUATION OF BIOLOGICAL OR FUNCTIONAL AGE IS KNOWN, SO IT IS THEREFORE NECESSARY TO MEASURE THE CONSEQUENCES OF ANTICANCER TREATMENT USING COMPLEX ASSESSMENTS. THE PRESENT REVIEW PRESENTS AN OVERVIEW OF PREMATURE AGING IN CCSS AND OF THE MECHANISMS INVOLVED IN ITS DEVELOPMENT, FOCUSING ON THE ASSOCIATION OF SENESCENCE AND LATE EFFECTS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
8 2855  59 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
9 1385  36 DIABETES IN CHILDHOOD CANCER SURVIVORS: EMERGING CONCEPTS IN PATHOPHYSIOLOGY AND FUTURE DIRECTIONS. WITH ADVANCEMENTS IN CANCER TREATMENT AND SUPPORTIVE CARE, THERE IS A GROWING POPULATION OF CHILDHOOD CANCER SURVIVORS WHO EXPERIENCE A SUBSTANTIAL BURDEN OF COMORBIDITIES RELATED TO HAVING RECEIVED CANCER TREATMENT AT A YOUNG AGE. DESPITE AN OVERALL REDUCTION IN THE INCIDENCE OF MOST CHRONIC HEALTH CONDITIONS IN CHILDHOOD CANCER SURVIVORS OVER THE PAST SEVERAL DECADES, THE CUMULATIVE INCIDENCE OF CERTAIN LATE EFFECTS, IN PARTICULAR DIABETES MELLITUS (DM), HAS INCREASED. THE IMPLICATIONS ARE SIGNIFICANT, BECAUSE DM IS A KEY RISK FACTOR FOR CARDIOVASCULAR DISEASE, A LEADING CAUSE OF PREMATURE DEATH IN CHILDHOOD CANCER SURVIVORS. THE UNDERLYING PATHOPHYSIOLOGY OF DM IN CANCER SURVIVORS IS MULTIFACTORIAL. DM DEVELOPS AT YOUNGER AGES IN SURVIVORS COMPARED TO CONTROLS, WHICH MAY REFLECT AN "ACCELERATED AGING" PHENOTYPE IN THESE INDIVIDUALS. THE TREATMENT-RELATED EXPOSURES (I.E., CHEMOTHERAPY, RADIATION) THAT INCREASE RISK FOR DM IN CHILDHOOD CANCER SURVIVORS MAY BE MORE THAN ADDITIVE WITH ESTABLISHED DM RISK FACTORS (E.G., OLDER AGE, OBESITY, RACE, AND ETHNICITY). EMERGING RESEARCH ALSO POINTS TO PARALLELS IN CELLULAR PROCESSES IMPLICATED IN AGING- AND CANCER TREATMENT-RELATED DM. STILL, THERE REMAINS MARKED INTER-INDIVIDUAL VARIABILITY REGARDING RISK OF DM THAT IS NOT EXPLAINED BY DEMOGRAPHIC AND THERAPEUTIC RISK FACTORS ALONE. RECENT STUDIES HAVE HIGHLIGHTED THE ROLE OF GERMLINE GENETIC RISK FACTORS AND EPIGENETIC MODIFICATIONS THAT ARE ASSOCIATED WITH RISK OF DM IN BOTH THE GENERAL AND ONCOLOGY POPULATIONS. THIS REVIEW SUMMARIZES OUR CURRENT UNDERSTANDING OF RECOGNIZED RISK FACTORS FOR DM IN CHILDHOOD CANCER SURVIVORS TO HELP INFORM TARGETED APPROACHES FOR DISEASE SCREENING, PREVENTION, AND TREATMENT. FURTHERMORE, IT HIGHLIGHTS THE EXISTING SCIENTIFIC GAPS IN UNDERSTANDING THE RELATIVE CONTRIBUTIONS OF INDIVIDUAL THERAPEUTIC EXPOSURES AND THE MECHANISMS BY WHICH THEY EXERT THEIR EFFECTS THAT UNIQUELY PREDISPOSE THIS POPULATION TO DM FOLLOWING CANCER TREATMENT.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
10  637  28 BIOLOGY OF PREMATURE AGEING IN SURVIVORS OF CANCER. OVER 30 MILLION CANCER SURVIVORS EXIST WORLDWIDE. SURVIVORS HAVE AN EARLIER ONSET AND HIGHER INCIDENCE OF CHRONIC COMORBIDITIES, INCLUDING ENDOCRINOPATHIES, CARDIAC DYSFUNCTION, OSTEOPOROSIS, PULMONARY FIBROSIS, SECONDARY CANCERS AND FRAILTY THAN THE GENERAL POPULATION; HOWEVER, THE FUNDAMENTAL BASIS OF THESE CHANGES AT THE CELLULAR LEVEL IS UNKNOWN. AN ELECTRONIC SEARCH WAS PERFORMED ON EMBASE, MEDLINE IN-PROCESS & OTHER NON-INDEXED CITATIONS, AND THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS. ORIGINAL ARTICLES ADDRESSING THE CELLULAR BIOLOGY OF AGEING AND/OR THE MECHANISMS OF CANCER THERAPIES SIMILAR TO AGEING MECHANISMS WERE INCLUDED, AND REFERENCES OF THESE ARTICLES WERE REVIEWED FOR FURTHER SEARCH. WE FOUND MULTIPLE BIOLOGICAL PROCESS OF AGEING AT THE CELLULAR LEVEL AND THEIR ASSOCIATION WITH CANCER THERAPIES, AS WELL AS WITH CLINICAL EFFECTS. THE DIRECT EFFECTS OF VARIOUS CHEMOTHERAPIES AND RADIATION ON TELOMERE LENGTH, SENESCENT CELLS, EPIGENETIC MODIFICATIONS AND MICRORNA WERE FOUND. WE REVIEW THE EFFECTS OF CANCER THERAPIES ON RECOGNISED HALLMARKS OF AGEING. LONG-TERM COMORBIDITIES SEEN IN CANCER SURVIVORS MIMIC THE PHENOTYPES OF AGEING AND LIKELY RESULT FROM THE INTERACTION BETWEEN THERAPEUTIC EXPOSURES AND THE UNDERLYING BIOLOGY OF AGEING. LONG-TERM FOLLOW-UP OF CANCER SURVIVORS AND RESEARCH ON PREVENTION STRATEGIES SHOULD BE PURSUED TO INCREASE THE LENGTH AND QUALITY OF LIFE AMONG THE GROWING POPULATION OF CANCER SURVIVORS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
11 1958  32 EPIGENETIC AGING AND COLORECTAL CANCER: STATE OF THE ART AND PERSPECTIVES FOR FUTURE RESEARCH. ALTHOUGH TRANSLATIONAL RESEARCH HAS IDENTIFIED A LARGE NUMBER OF POTENTIAL BIOMARKERS INVOLVED IN COLORECTAL CANCER (CRC) CARCINOGENESIS, A BETTER UNDERSTANDING OF THE MOLECULAR PATHWAYS ASSOCIATED WITH BIOLOGICAL AGING IN COLORECTAL CELLS AND TISSUES IS NEEDED. HERE, WE AIM TO SUMMARIZE THE STATE OF THE ART ABOUT THE ROLE OF AGE ACCELERATION, DEFINED AS THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, IN THE DEVELOPMENT AND PROGRESSION OF CRC. SOME STUDIES HAVE SHOWN THAT ACCELERATED BIOLOGICAL AGING IS POSITIVELY ASSOCIATED WITH THE RISK OF CANCER AND DEATH IN GENERAL. IN LINE WITH THESE FINDINGS, OTHER STUDIES HAVE SHOWN HOW THE ASSESSMENT OF EPIGENETIC AGE IN PEOPLE AT RISK FOR CRC COULD BE HELPFUL FOR MONITORING THE MOLECULAR RESPONSE TO PREVENTIVE INTERVENTIONS. MOREOVER, IT WOULD BE INTERESTING TO INVESTIGATE WHETHER ABERRANT EPIGENETIC AGING COULD HELP IDENTIFY CRC PATIENTS WITH A HIGH RISK OF RECURRENCE AND A WORST PROGNOSIS, AS WELL AS THOSE WHO RESPOND POORLY TO TREATMENT. YET, THE APPLICATION OF THIS NOVEL CONCEPT IS STILL IN ITS INFANCY, AND FURTHER RESEARCH SHOULD BE ENCOURAGED IN ANTICIPATION OF FUTURE APPLICATIONS IN CLINICAL PRACTICE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
12 5076  37 PHYSIOLOGICAL AND ENVIRONMENTAL FACTORS AFFECTING CANCER RISK AND PROGNOSIS IN OBESITY. OBESITY RESULTS FROM A CHRONIC EXCESSIVE ACCUMULATION OF ADIPOSE TISSUE DUE TO A LONG-TERM IMBALANCE BETWEEN ENERGY INTAKE AND EXPENDITURE. AVAILABLE EPIDEMIOLOGICAL AND CLINICAL DATA STRONGLY SUPPORT THE LINKS BETWEEN OBESITY AND CERTAIN CANCERS. EMERGING CLINICAL AND EXPERIMENTAL FINDINGS HAVE IMPROVED OUR UNDERSTANDING OF THE ROLES OF KEY PLAYERS IN OBESITY-ASSOCIATED CARCINOGENESIS SUCH AS AGE, SEX (MENOPAUSE), GENETIC AND EPIGENETIC FACTORS, GUT MICROBIOTA AND METABOLIC FACTORS, BODY SHAPE TRAJECTORY OVER LIFE, DIETARY HABITS, AND GENERAL LIFESTYLE. IT IS NOW WIDELY ACCEPTED THAT THE CANCER-OBESITY RELATIONSHIP DEPENDS ON THE SITE OF CANCER, THE SYSTEMIC INFLAMMATORY STATUS, AND MICRO ENVIRONMENTAL PARAMETERS SUCH AS LEVELS OF INFLAMMATION AND OXIDATIVE STRESS IN TRANSFORMING TISSUES. WE HEREBY REVIEW RECENT ADVANCES IN OUR UNDERSTANDING OF CANCER RISK AND PROGNOSIS IN OBESITY WITH RESPECT TO THESE PLAYERS. WE HIGHLIGHT HOW THE LACK OF THEIR CONSIDERATION CONTRIBUTED TO THE CONTROVERSY OVER THE LINK BETWEEN OBESITY AND CANCER IN EARLY EPIDEMIOLOGICAL STUDIES. FINALLY, THE LESSONS AND CHALLENGES OF INTERVENTIONS FOR WEIGHT LOSS AND BETTER CANCER PROGNOSIS, AND THE MECHANISMS OF WEIGHT GAIN IN SURVIVORS ARE ALSO DISCUSSED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
13 4787  43 NUTRITION, AGING AND CANCER: LESSONS FROM DIETARY INTERVENTION STUDIES. THERE IS CONVINCING EPIDEMIOLOGICAL AND CLINICAL EVIDENCE THAT, INDEPENDENT OF AGING, LIFESTYLE AND, NOTABLY, NUTRITION ARE ASSOCIATED WITH DEVELOPMENT OR PROGRESSION OF MAJOR HUMAN CANCERS, INCLUDING BREAST, PROSTATE, COLORECTAL TUMORS, AND AN INCREASINGLY LARGE COLLECTION OF DIET-RELATED CANCERS. MECHANISMS UNDERLYING THIS ASSOCIATION ARE MOSTLY RELATED TO THE DISTINCT EPIGENETIC EFFECTS OF DIFFERENT DIETARY PATTERNS. IN THIS CONTEXT, MEDITERRANEAN DIET HAS BEEN REPORTED TO SIGNIFICANTLY REDUCE MORTALITY RATES FOR VARIOUS CHRONIC ILLNESSES, INCLUDING CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES AND CANCER. ALTHOUGH MANY OBSERVATIONAL STUDIES HAVE SUPPORTED THIS EVIDENCE, DIETARY INTERVENTION STUDIES USING A MEDITERRANEAN DIETARY PATTERN OR ITS SELECTED FOOD COMPONENTS ARE STILL LIMITED AND AFFECTED BY A RATHER LARGE VARIABILITY IN CHARACTERISTICS OF STUDY SUBJECTS, TYPE AND LENGTH OF INTERVENTION, SELECTED END-POINTS AND STATISTICAL ANALYSIS. HERE WE REVIEW DATA OF TWO OF OUR INTERVENTION STUDIES, THE MEDIET STUDY AND THE DIMESA PROJECT, AIMED AT ASSESSING THE EFFECTS OF TRADITIONAL MEDITERRANEAN DIET AND/OR ITS COMPONENT(S) ON A LARGE PANEL OF BOTH PLASMA AND URINE BIOMARKERS. BOTH PUBLISHED AND UNPUBLISHED RESULTS ARE PRESENTED AND DISCUSSED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
14 5072  39 PHYSICAL EXERCISE POSITIVELY INFLUENCES BREAST CANCER EVOLUTION. BREAST CANCER IS ONE OF THE MOST COMMONLY DIAGNOSED TYPES OF CANCER IN WOMEN. ITS PATHOGENESIS INVOLVES GENETIC, HORMONAL, AND ENVIRONMENTAL FACTORS. A LARGE BODY OF EVIDENCE INDICATES THAT PHYSICAL ACTIVITY HAS POSITIVE EFFECTS ON EVERY ASPECT OF BREAST CANCER EVOLUTION, INCLUDING PREVENTION, MEDICAL TREATMENT, AND AFTERCARE CLINICAL SETTINGS. THUS, DIFFERENT TYPES OF EXERCISE CAN INFLUENCE THE PREVENTION AND PROGRESSION OF THE DISEASE THROUGH SEVERAL COMMON MECHANISMS, SUCH AS REDUCTION OF INSULIN RESISTANCE AND IMPROVEMENT OF IMMUNITY AND CARDIOVASCULAR FUNCTION. FURTHERMORE, ACUTE AND CHRONIC SYMPTOMS OF BREAST CANCER, SUCH AS CACHEXIA, MUSCLE MASS LOSS, FATIGUE, CARDIOTOXICITY, WEIGHT GAIN, HORMONE ALTERATIONS, BONE LOSS, AND PSYCHOLOGIC ADVERSE EFFECTS, MAY ALL BE FAVORABLY INFLUENCED BY REGULAR EXERCISE. WE REVIEW THE RELATION OF INTENSITY AND DURATION OF EXERCISE WITH POTENTIAL PATHOPHYSIOLOGIC PATHWAYS, INCLUDING OBESITY-RELATED HORMONES AND SEX STEROID HORMONE PRODUCTION, OXIDATIVE STRESS, EPIGENETIC ALTERATIONS SUCH AS DNA HYPOMETHYLATION, AND CHANGES IN TELOMERE LENGTH, WITHIN THE CONTEXT OF THE BENEFICIAL EFFECTS OF EXERCISE. THE POTENTIAL ROLE OF EXERCISE IN REDUCING THE INTENSITY OF THE ADVERSE EFFECTS THAT RESULT FROM BREAST CANCER AND ANTICANCER TREATMENT IS ALSO DISCUSSED.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
15 6823  31 [GENERAL CONCEPTS OF EPIGENETICS: PROJECTIONS IN PAEDIATRICS]. CURRENT EVIDENCE SUPPORTS THE NOTION THAT ALTERATIONS IN INTRAUTERINE GROWTH AND DURING THE FIRST YEARS OF LIFE HAVE A SUBSTANTIAL EFFECT ON THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASE, WHICH IN SOME CASES IS EVEN HIGHER THAN THOSE DUE TO GENETIC FACTORS. THE PERSISTENCE AND REPRODUCIBILITY OF THE PHENOTYPES ASSOCIATED WITH ALTERED EARLY DEVELOPMENT SUGGEST THE PARTICIPATION OF MECHANISMS THAT WOULD RECORD ENVIRONMENTAL CUES, GENERATING A CELLULAR REPROGRAMMING (I.E., EPIGENETIC MECHANISMS). THIS REVIEW IS AN INTRODUCTION TO A SERIES OF FIVE ARTICLES FOCUSED ON THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF HIGHLY PREVALENT CHRONIC DISEASES (I.E., CARDIOVASCULAR, METABOLIC, ASTHMA/ALLERGIES AND CANCER) AND THEIR ORIGINS IN THE FOETAL AND NEONATAL PERIOD. THIS SERIES OF ARTICLES AIMS TO SHOW THE STATE OF THE ART IN THIS RESEARCH AREA AND PRESENT THE UPCOMING CLUES AND CHALLENGES, IN WHICH PAEDIATRICIANS HAVE A PROMINENT ROLE, DEVELOPING STRATEGIES FOR THE PREVENTION, EARLY DETECTION AND FOLLOW-UP.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
16 1206  40 COUNTERACTING AGED DNA METHYLATION STATES TO COMBAT AGEING AND AGE-RELATED DISEASES. DNA METHYLATION (DNAM) OVERWRITES INFORMATION ABOUT MULTIPLE EXTRINSIC FACTORS ON THE GENOME. AGE IS ONE OF THESE FACTORS. AGE CAUSES CHARACTERISTIC DNAM CHANGES THAT ARE THOUGHT TO BE NOT ONLY MAJOR DRIVERS OF NORMAL AGEING BUT ALSO PRECURSORS TO DISEASES, CANCER BEING ONE OF THESE. ALTHOUGH THERE IS STILL MUCH TO LEARN ABOUT THE RELATIONSHIP BETWEEN AGEING, AGE-RELATED DISEASES AND DNAM, WE NOW KNOW HOW TO INTERPRET SOME OF THE EFFECTS CAUSED BY AGE IN THE FORM OF CHANGES IN METHYLATION MARKS AT SPECIFIC LOCI. IN FACT, THESE CHANGES FORM THE BASIS OF THE SO CALLED "EPIGENETIC CLOCKS", WHICH TRANSLATE THE GENOMIC METHYLATION PROFILE INTO AN "EPIGENETIC AGE". EPIGENETIC AGE DOES NOT ONLY ESTIMATE CHRONOLOGICAL AGE BUT CAN ALSO PREDICT THE RISK OF CHRONIC DISEASES AND MORTALITY. EPIGENETIC AGE IS BELIEVED TO BE ONE OF THE MOST ACCURATE METRICS OF BIOLOGICAL AGE. INITIAL EVIDENCE HAS RECENTLY BEEN GATHERED POINTING TO THE POSSIBILITY THAT THE RATE OF EPIGENETIC AGEING CAN BE SLOWED DOWN OR EVEN REVERSED. IN THIS REVIEW, WE DISCUSS SOME OF THE MOST RELEVANT ADVANCES IN THIS FIELD. EXPECTED OUTCOME IS THAT THIS APPROACH CAN PROVIDE INSIGHTS INTO HOW TO PRESERVE HEALTH AND REDUCE THE IMPACT OF AGEING DISEASES IN HUMANS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
17 1360  45 DEVELOPMENTAL ASPECTS OF A LIFE COURSE APPROACH TO HEALTHY AGEING. WE EXAMINE THE MECHANISTIC BASIS AND WIDER IMPLICATIONS OF ADOPTING A DEVELOPMENTAL PERSPECTIVE ON HUMAN AGEING. PREVIOUS MODELS OF AGEING HAVE CONCENTRATED ON ITS GENETIC BASIS, OR THE DETRIMENTAL EFFECTS OF ACCUMULATED DAMAGE, BUT ALSO HAVE RAISED ISSUES ABOUT WHETHER AGEING CAN BE VIEWED AS ADAPTIVE ITSELF, OR IS A CONSEQUENCE OF OTHER ADAPTIVE PROCESSES, FOR EXAMPLE IF MAINTENANCE AND REPAIR PROCESSES IN THE PERIOD UP TO REPRODUCTION ARE TRADED OFF AGAINST LATER DECLINE IN FUNCTION. A LIFE COURSE MODEL PLACES AGEING IN THE CONTEXT OF THE ATTAINMENT OF PEAK CAPACITY FOR A BODY SYSTEM, STARTING IN EARLY DEVELOPMENT WHEN PLASTICITY PERMITS CHANGES IN STRUCTURE AND FUNCTION INDUCED BY A RANGE OF ENVIRONMENTAL STIMULI, FOLLOWED BY A PERIOD OF DECLINE, THE RATE OF WHICH DEPENDS ON THE PEAK ATTAINED AS WELL AS THE LATER LIFE CONDITIONS. SUCH PATH DEPENDENCY IN THE RATE OF AGEING MAY OFFER NEW INSIGHTS INTO ITS MODIFICATION. FOCUSING ON MUSCULOSKELETAL AND CARDIOVASCULAR FUNCTION, WE DISCUSS THIS MODEL AND THE POSSIBLE UNDERLYING MECHANISMS, INCLUDING ENDOTHELIAL FUNCTION, OXIDATIVE STRESS, STEM CELLS AND NUTRITIONAL FACTORS SUCH AS VITAMIN D STATUS. EPIGENETIC CHANGES INDUCED DURING DEVELOPMENTAL PLASTICITY, AND IMMUNE FUNCTION MAY PROVIDE A COMMON MECHANISTIC PROCESS UNDERLYING A LIFE COURSE MODEL OF AGEING. THE LIFE COURSE TRAJECTORY DIFFERS IN HIGH AND LOW RESOURCE SETTINGS. NEW INSIGHTS INTO THE DEVELOPMENTAL COMPONENTS OF THE LIFE COURSE MODEL OF AGEING MAY LEAD TO THE DESIGN OF BIOMARKERS OF LATER CHRONIC DISEASE RISK AND TO NEW INTERVENTIONS TO PROMOTE HEALTHY AGEING, WITH IMPORTANT IMPLICATIONS FOR PUBLIC HEALTH.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
18 6781  54 [BREATHING: AMBIENT AIR POLLUTION AND HEALTH - PART III]. THE THIRD PART OF THE DGP STATEMENT INTRODUCES THE CURRENT BODY OF KNOWLEDGE ON LESS STUDIED HEALTH OUTCOMES ASSOCIATED WITH EXPOSURE TO AMBIENT AIR POLLUTION: THE NEGATIVE IMPACT ON METABOLISM LEADING TO IMPAIRED GLUCOSE TOLERANCE AND DIABETES AS WELL AS CONTRIBUTION TO THE DEVELOPMENT OF NEURODEGENERATIVE DISORDERS AND DELAYED COGNITIVE FUNCTION IN CHILDREN. FURTHERMORE, PRENATAL EXPOSURE AND ADVERSE EFFECTS ON MOTHER AND CHILD ARE ADDRESSED. FINALLY, THE CURRENTLY DISCUSSED BIOLOGICAL MECHANISMS UNDERLYING VARIOUS HEALTH EFFECTS ASSOCIATED WITH EXPOSURE TO AIR POLLUTION ARE DESCRIBED.DIFFERING, BUT OFTEN COMPLEMENTARY BIOLOGICAL MECHANISMS CREATE THE BASIS FOR THE DIVERSE HEALTH OUTCOMES CAUSED BY AIR POLLUTION. OXIDATIVE STRESS AND A SUBCLINICAL INFLAMMATORY RESPONSE IN THE LUNGS AND ON A SYSTEMIC LEVEL ("LOW-GRADE SYSTEMIC INFLAMMATION") ARE CONSIDERED TO BE KEY MECHANISMS. THEY PROMOTE SECONDARY ALTERATIONS IN THE BODY, SUCH AS VASCULAR OR METABOLIC PROCESSES, AND MAY ALSO RESULT IN THE CURRENTLY STUDIED EPIGENETIC PHENOMENA OR NEUROINFLAMMATION. IN THIS CONTEXT, THE HEALTH SIGNIFICANCE OF SOLUBLE PARTICULATE MATTER AND THE ROLE OF ULTRAFINE PARTICLES TRANSLOCATED ACROSS BIOLOGICAL MEMBRANES INTO BLOOD VESSEL AND TRANSPORTED VIA THE CIRCULATION TO SECONDARY TARGET ORGANS, SUCH AS LIVER, BRAIN OR THE FETUS, ARE INTENSIVELY DISCUSSED.DIABETES IS ONE OF THE LEADING CHRONIC DISEASES WORLDWIDE, WITH A PREVALENCE OF ALMOST 14 % IN GERMANY. ALTHOUGH LIFESTYLE FACTORS ARE THE MAIN CAUSES, CURRENT EVIDENCE SUGGESTS THAT LONG-TERM EXPOSURE TO AIR POLLUTION MAY ADDITIONALLY INCREASE THE RISK FOR TYPE 2 DIABETES. SUPPORTING EVIDENCE FOR A CAUSAL ROLE OF AIR POLLUTION IS PROVIDED BY STUDIES ADDRESSING THE REGULATION OF THE BLOOD GLUCOSE LEVELS IN METABOLICALLY HEALTHY PARTICIPANTS, INSULIN SENSITIVITY, OR PREGNANCY-RELATED DIABETES. EXPERIMENTAL STUDIES PROVIDE FURTHER SUPPORT FOR PLAUSIBLE BIOLOGICAL MECHANISMS. HOWEVER, PROSPECTIVE STUDIES ARE NEEDED TO GAIN MORE EVIDENCE, TAKING MULTIPLE LIFESTYLE AND ENVIRONMENTAL FACTORS, SUCH AS GREEN SPACE AND NOISE, AND AN IMPROVED INDIVIDUAL EXPOSURE ASSESSMENT INTO ACCOUNT.THE AGING POPULATION HAS AN INCREASED RISK OF NEURODEGENERATIVE DISEASES. FIRST STUDIES POINT TOWARDS A CONTRIBUTION OF CHRONIC EXPOSURE TO AIR POLLUTION, SPECIFICALLY BY PARTICULATE MATTER. SEVERAL STUDIES REPORT ITS ASSOCIATION WITH DECREASED NEUROCOGNITIVE CAPACITY OR AN INCREASED PREVALENCE OF DEMENTIA OR ALZHEIMER'S DISEASE IN ADULTS. HOWEVER, THE STUDIES ARE INHOMOGENEOUS REGARDING DESIGN, EXPOSURE AND OUTCOME, LEADING TO INCONSISTENT RESULTS. WITH RESPECT TO THE INFLUENCE ON NEUROCOGNITIVE DEVELOPMENT OF CHILDREN, FIRST STUDIES SUGGEST AN ASSOCIATION BETWEEN THE LEVEL OF AIR POLLUTION, E. G. AT SCHOOL, AND DELAYED COGNITIVE DEVELOPMENT.EVEN THOUGH THE EVIDENCE FOR THE DIFFERENT BIOLOGICAL ENDPOINTS DURING PREGNANCY IS STILL HETEROGENEOUS, THE STUDIES GENERALLY POINT TOWARDS AN ADVERSE IMPACT OF AIR POLLUTION ON THE MATERNAL AND FETAL ORGANISMS. THE STRONGEST EVIDENCE EXISTS FOR LOW BIRTH WEIGHT, WITH SMALL EFFECT SIZES OF ONLY SOME GRAMS, AND FOR A HIGHER INCIDENCE OF REDUCED BIRTH WEIGHT (< 2500 G). AN INCREASED RISK FOR GESTATIONAL HYPERTENSION AND PREECLAMPSIA UNDERSCORES THE POSSIBLE IMPACT OF EXPOSURE TO AIR POLLUTION ON THE MATERNAL ORGANISM. HOWEVER, THE CURRENT BODY OF EVIDENCE DOES NOT YET ALLOW A FINAL CONCLUSION ON THE INFLUENCE OF INTRAUTERINE EXPOSURE TO AIR POLLUTION REGARDING EARLY CHILDHOOD LUNG FUNCTION AND DEVELOPMENT OF ALLERGIES, PARTICULARLY IN LIGHT OF THE FACT THAT IT IS HARD TO DISTINGUISH IN EPIDEMIOLOGICAL STUDIES BETWEEN THE EFFECTS OF PRE- AND POSTNATAL EXPOSURE.	2019	

19  456  47 APPLYING A LIFE COURSE BIOLOGICAL AGE FRAMEWORK TO IMPROVING THE CARE OF INDIVIDUALS WITH ADULT CANCERS: REVIEW AND RESEARCH RECOMMENDATIONS. IMPORTANCE: THE PRACTICE OF ONCOLOGY WILL INCREASINGLY INVOLVE THE CARE OF A GROWING POPULATION OF INDIVIDUALS WITH MIDLIFE AND LATE-LIFE CANCERS. MANAGING CANCER IN THESE INDIVIDUALS IS COMPLEX, BASED ON DIFFERENCES IN BIOLOGICAL AGE AT DIAGNOSIS. BIOLOGICAL AGE IS A MEASURE OF ACCUMULATED LIFE COURSE DAMAGE TO BIOLOGICAL SYSTEMS, LOSS OF RESERVE, AND VULNERABILITY TO FUNCTIONAL DETERIORATION AND DEATH. BIOLOGICAL AGE IS IMPORTANT BECAUSE IT AFFECTS THE ABILITY TO MANAGE THE RIGORS OF CANCER THERAPY, SURVIVORS' FUNCTION, AND CANCER PROGRESSION. HOWEVER, BIOLOGICAL AGE IS NOT ALWAYS CLINICALLY APPARENT. THIS REVIEW PRESENTS A CONCEPTUAL FRAMEWORK OF LIFE COURSE BIOLOGICAL AGING, SUMMARIZES CANDIDATE MEASURES, AND DESCRIBES A RESEARCH AGENDA TO FACILITATE CLINICAL TRANSLATION TO ONCOLOGY PRACTICE. OBSERVATIONS: MIDLIFE AND LATE-LIFE CANCERS ARE CHRONIC DISEASES THAT MAY ARISE FROM CUMULATIVE PATTERNS OF BIOLOGICAL AGING OCCURRING OVER THE LIFE COURSE. BEFORE DIAGNOSIS, EACH NEW PATIENT WAS ON A DISTINCT COURSE OF BIOLOGICAL AGING RELATED TO PAST EXPOSURES, LIFE EXPERIENCES, GENETICS, AND NONCANCER CHRONIC DISEASE. CANCER AND ITS TREATMENTS MAY ALSO BE ASSOCIATED WITH BIOLOGICAL AGING. SEVERAL MEASURES OF BIOLOGICAL AGE, INCLUDING P16INK4A, EPIGENETIC AGE, TELOMERE LENGTH, AND INFLAMMATORY AND BODY COMPOSITION MARKERS, HAVE BEEN USED IN ONCOLOGY RESEARCH. ONE OR MORE OF THESE MEASURES MAY BE USEFUL IN CANCER CARE, EITHER ALONE OR IN COMBINATION WITH CLINICAL HISTORY AND GERIATRIC ASSESSMENTS. HOWEVER, FURTHER RESEARCH WILL BE NEEDED BEFORE BIOLOGICAL AGE ASSESSMENT CAN BE RECOMMENDED IN ROUTINE PRACTICE, INCLUDING DETERMINATION OF SITUATIONS IN WHICH KNOWLEDGE ABOUT BIOLOGICAL AGE WOULD CHANGE TREATMENT, ASCERTAINING WHETHER TREATMENT EFFECTS ON BIOLOGICAL AGING ARE SHORT-LIVED OR PERSISTENT, AND TESTING INTERVENTIONS TO MODIFY BIOLOGICAL AGE, DECREASE TREATMENT TOXIC EFFECTS, AND MAINTAIN FUNCTIONAL ABILITIES. CONCLUSIONS AND RELEVANCE: UNDERSTANDING DIFFERENCES IN BIOLOGICAL AGING COULD ULTIMATELY ALLOW CLINICIANS TO BETTER PERSONALIZE TREATMENT AND SUPPORTIVE CARE, DEVELOP TAILORED SURVIVORSHIP CARE PLANS, AND PRESCRIBE PREVENTIVE OR AMELIORATIVE THERAPIES AND BEHAVIORS INFORMED BY AGING MECHANISMS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
20 3915  39 LINE-1 IN OBESITY AND CARDIOMETABOLIC DISEASES: A SYSTEMATIC REVIEW. EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES, BY ACTIVATING OR SILENCING THE RELATED-GENES. SCIENTIFIC EVIDENCE HAS SUGGESTED THAT LINE-1 METHYLATION IS ASSOCIATED WITH BODY COMPOSITION AND OBESITY-RELATED DISEASES, INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE (CVD). IT ALSO HAS BEEN EVALUATED AS PREDICTOR OF WEIGHT LOSS. THE STUDIES' RESULTS ARE STILL CONFLICTING, AND POSITIVE AND NEGATIVE ASSOCIATIONS HAVE BEEN FOUND TO LINE-1 METHYLATION REGARDING ADIPOSITY AND CARDIOMETABOLIC MARKERS. OVERALL, THIS REVIEW PRESENTS OBSERVATIONAL (CROSS-SECTIONAL AND LONGITUDINAL) STUDIES AND INTERVENTIONS (DIET, EXERCISES, AND BARIATRIC SURGERY) THAT EVALUATED THE RELATIONSHIP OF THE LINE-1 METHYLATION WITH OBESITY, WEIGHT LOSS, DYSLIPIDEMIAS, HYPERTENSION, INSULIN RESISTANCE, CVD, AND METABOLIC SYNDROME. TEACHING POINTS EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF OBESITY AND CARDIOMETABOLIC DISEASES. MANY STUDIES HAVE RELATED METHYLATION OF LINE-1 WITH CARDIOMETABOLIC DISEASES; HOWEVER, THE RESULTS ARE STILL CONTROVERSIAL. THE RELATIONSHIP BETWEEN THE ETIOLOGY OF CHRONIC DISEASES AND THE METHYLATION OF LINE-1 IS NOT FULLY ELUCIDATED. WITH ADVANCES IN EPIGENETIC STUDIES, RELATED MECHANISMS MAY BE EARLY BIOMARKERS IN WEIGHT CHANGE AND CARDIOMETABOLIC RISK.	2019