1 5757 129 SOCIOECONOMIC STATUS, KNEE PAIN, AND EPIGENETIC AGING IN COMMUNITY-DWELLING MIDDLE-TO-OLDER AGE ADULTS. CHRONIC MUSCULOSKELETAL PAIN IS OFTEN ASSOCIATED WITH LOWER SOCIOECONOMIC STATUS (SES). SES CORRELATES WITH PSYCHOLOGICAL AND ENVIRONMENTAL CONDITIONS THAT COULD CONTRIBUTE TO THE DISPROPORTIONATE BURDEN OF CHRONIC STRESS. CHRONIC STRESS CAN INDUCE CHANGES IN GLOBAL DNA METHYLATION AND GENE EXPRESSION, WHICH INCREASES RISK OF CHRONIC PAIN. WE AIMED TO EXPLORE THE ASSOCIATION OF EPIGENETIC AGING AND SES IN MIDDLE-TO-OLDER AGE INDIVIDUALS WITH VARYING DEGREES OF KNEE PAIN. PARTICIPANTS COMPLETED SELF-REPORTED PAIN, A BLOOD DRAW, AND ANSWERED DEMOGRAPHIC QUESTIONS PERTAINING TO SES. WE USED AN EPIGENETIC CLOCK PREVIOUSLY ASSOCIATED WITH KNEE PAIN (DNAMGRIMAGE) AND THE SUBSEQUENT DIFFERENCE OF PREDICTED EPIGENETIC AGE (DNAMGRIMAGE-DIFF). OVERALL, THE MEAN DNAMGRIMAGE WAS 60.3 (+/-7.6), AND THE AVERAGE DNAMGRIMAGE-DIFF WAS 2.4 YEARS (+/-5.6 YEARS). THOSE EXPERIENCING HIGH-IMPACT PAIN EARNED LESS INCOME AND HAD LOWER EDUCATION LEVELS COMPARED TO BOTH LOW-IMPACT AND NO PAIN GROUPS. DIFFERENCES IN DNAMGRIMAGE-DIFF ACROSS PAIN GROUPS WERE FOUND, WHEREBY INDIVIDUALS WITH HIGH-IMPACT PAIN HAD ACCELERATED EPIGENETIC AGING ( APPROXIMATELY 5 YEARS) COMPARED TO LOW-IMPACT PAIN AND NO PAIN CONTROL GROUPS (BOTH APPROXIMATELY 1 YEAR). OUR MAIN FINDING WAS THAT EPIGENETIC AGING MEDIATED THE ASSOCIATIONS OF INCOME AND EDUCATION WITH PAIN IMPACT, AS SUCH THE RELATIONSHIP BETWEEN SES AND PAIN OUTCOMES MAY OCCUR THROUGH POTENTIAL INTERACTIONS WITH THE EPIGENOME REFLECTIVE OF ACCELERATED CELLULAR AGING. PERSPECTIVE: SOCIOECONOMIC STATUS (SES) HAS PREVIOUSLY BEEN IMPLICATED IN THE PAIN EXPERIENCE. THE PRESENT MANUSCRIPT AIMS TO PRESENT A POTENTIAL SOCIAL-BIOLOGICAL LINK BETWEEN SES AND PAIN VIA ACCELERATED EPIGENETIC AGING.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2 1964  44 EPIGENETIC AGING, KNEE PAIN AND PHYSICAL PERFORMANCE IN COMMUNITY-DWELLING MIDDLE-TO-OLDER AGE ADULTS. KNEE PAIN IS A LEADING CAUSE OF DISABILITY IN THE AGING POPULATION AND MAY INDIRECTLY ACCELERATE BIOLOGICAL AGING PROCESSES. CHRONOLOGICAL AGING INCREASES THE RISK OF DEVELOPING OF KNEE PAIN AND KNEE PAIN REDUCES PHYSICAL FUNCTION; HOWEVER, LIMITED DATA EXIST ON HOW EPIGENETIC AGING, A KNOWN HALLMARK OF BIOLOGICAL AGING SHOWN TO PREDICT HEALTH SPAN AND MORTALITY, MAY INFLUENCE THIS RELATIONSHIP. THE PURPOSE OF THIS STUDY WAS TO EXAMINE WHETHER DECREASED PHYSICAL PERFORMANCE ASSOCIATED WITH KNEE PAIN IS MEDIATED BY MARKERS OF EPIGENETIC AGING. PARTICIPANTS (57.91 +/- 8.04 YEARS) WITH LOW IMPACT KNEE PAIN (N = 95), HIGH IMPACT KNEE PAIN (N = 53) AND PAIN-FREE CONTROLS (N = 26) COMPLETED SELF-REPORTED PAIN, A BLOOD DRAW AND A SHORT PHYSICAL PERFORMANCE BATTERY (SPPB) THAT INCLUDED BALANCE, WALKING, AND SIT TO STAND TASKS. WE EMPLOYED AN EPIGENETIC CLOCK PREVIOUSLY ASSOCIATED WITH KNEE PAIN AND SHOWN TO PREDICT OVERALL MORTALITY RISK (DNAMGRIMAGE). BOOTSTRAPPED-MEDIATION ANALYSES WERE USED TO DETERMINE ASSOCIATIONS OF DNAMGRIMAGE AND SPPB BETWEEN PAIN GROUPS. THOSE WITH HIGH IMPACT AND LOW IMPACT PAIN HAD A BIOLOGICALLY OLDER EPIGENETIC AGE (5.14Y +/- 5.66 AND 1.32Y +/- 5.41, RESPECTIVELY). HOWEVER, WHILE THERE WERE DIRECT EFFECTS OF PAIN ON OVERALL PHYSICAL PERFORMANCE, THESE WERE NOT EXPLAINED BY EPIGENETIC AGING. EPIGENETIC AGING ONLY MEDIATED THE EFFECT OF PAIN ON BALANCE PERFORMANCE. FUTURE WORK IS NEEDED TO EXAMINE PAIN'S IMPACT ON BIOLOGICAL AGING PROCESSES INCLUDING EPIGENETIC AGING AND ITS ULTIMATE EFFECT ON PHYSICAL FUNCTION MEASURES KNOWN TO PREDICT HEALTH SPAN AND MORTALITY.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
3 1957  48 EPIGENETIC AGE PREDICTORS IN COMMUNITY-DWELLING ADULTS WITH HIGH IMPACT KNEE PAIN. GERONTOLOGICAL RESEARCH REVEALS CONSIDERABLE INTERINDIVIDUAL VARIABILITY IN AGING PHENOTYPES, AND EMERGING EVIDENCE SUGGESTS THAT HIGH IMPACT CHRONIC PAIN MAY BE ASSOCIATED WITH VARIOUS ACCELERATED BIOLOGICAL AGING PROCESSES. IN PARTICULAR, EPIGENETIC AGING IS A ROBUST PREDICTOR OF HEALTH-SPAN AND DISABILITY COMPARED TO CHRONOLOGICAL AGE ALONE. THE CURRENT STUDY AIMED TO DETERMINE WHETHER SEVERAL EPIGENETIC AGING BIOMARKERS WERE ASSOCIATED WITH HIGH IMPACT CHRONIC PAIN IN MIDDLE TO OLDER AGE ADULTS (44-78 YEARS OLD). PARTICIPANTS (N = 213) UNDERWENT A BLOOD DRAW, DEMOGRAPHIC, PSYCHOSOCIAL, PAIN AND FUNCTIONAL ASSESSMENTS. WE ESTIMATED FIVE EPIGENETIC CLOCKS AND CALCULATED THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, WHICH HAS BEEN PREVIOUSLY REPORTED TO PREDICT OVERALL MORTALITY RISK, AS WELL AS INCLUDED ADDITIONAL DERIVED VARIABLES OF EPIGENETIC AGE PREVIOUSLY ASSOCIATED WITH PAIN. THERE WERE SIGNIFICANT DIFFERENCES ACROSS PAIN IMPACT GROUPS IN THREE OUT OF THE FIVE EPIGENETIC CLOCKS EXAMINED (DNAMAGE, DNAMPHENOAGE AND DNAMGRIMAGE), INDICATING THAT PAIN-RELATED DISABILITY DURING THE PAST 6 MONTHS WAS ASSOCIATED WITH MARKERS OF EPIGENETIC AGING. ONLY DNAMPHENOAGE AND DNAMGRIMAGE WERE ASSOCIATED WITH HIGHER KNEE PAIN INTENSITY DURING THE PAST 48 H. FINALLY, PAIN CATASTROPHIZING, DEPRESSIVE SYMPTOMATOLOGY AND MORE NEUROPATHIC PAIN SYMPTOMS WERE SIGNIFICANTLY ASSOCIATED WITH AN OLDER EPIGENOME IN ONLY ONE OF THE FIVE EPIGENETIC CLOCKS (I.E. DNAMGRIMAGE) AFTER CORRECTING FOR MULTIPLE COMPARISONS (CORRECTED P'S < 0.05). GIVEN THE SCANT LITERATURE IN RELATION TO EPIGENETIC AGING AND THE COMPLEX EXPERIENCE OF PAIN, ADDITIONAL RESEARCH IS NEEDED TO UNDERSTAND WHETHER EPIGENETIC AGING MAY HELP IDENTIFY PEOPLE WITH CHRONIC PAIN AT GREATER RISK OF FUNCTIONAL DECLINE AND POORER HEALTH OUTCOMES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
4 1772  40 EARLY-LIFE SOCIOECONOMIC DISADVANTAGE, NOT CURRENT, PREDICTS ACCELERATED EPIGENETIC AGING OF MONOCYTES. LOW SOCIOECONOMIC STATUS (SES) IN EARLY-LIFE AND ADULTHOOD INDEPENDENTLY CONTRIBUTE TO INCREASED RISK FOR AGING-RELATED CHRONIC DISEASES. ONE MECHANISTIC HYPOTHESIS FOR THESE ASSOCIATIONS INVOLVES FASTER CELLULAR AGING OF IMMUNE CELLS, WHICH COULD PLAUSIBLY CONTRIBUTE TO CHRONIC DISEASE PATHOGENESIS BY COMPROMISING HOST RESISTANCE AND/OR UP-REGULATING INFLAMMATION. HOWEVER, LITTLE IS KNOWN ABOUT THE ASSOCIATION BETWEEN LIFE-COURSE SES AND CELLULAR AGING. THE PRESENT STUDY EXAMINES THE ASSOCIATION OF EARLY-LIFE AND CURRENT SES WITH A NOVEL BIOMARKER OF CELLULAR AGING TERMED THE "EPIGENETIC CLOCK," IN MONOCYTES. ADDITIONALLY, WE EXAMINE HEALTH BEHAVIORS AND DEPRESSIVE SYMPTOMS AS POTENTIAL EXPLANATORY PATHWAYS. THE STUDY INVOLVED 335 PARTICIPANTS BETWEEN THE AGES OF 15 AND 55 FROM VANCOUVER, CANADA AND SURROUNDING AREAS. ENROLLED PARTICIPANTS HAD TO FIT INTO FOUR LIFE-COURSE SES TRAJECTORIES, CORRESPONDING TO LOW-LOW, LOW-HIGH, HIGH-LOW AND HIGH-HIGH COMBINATIONS OF EARLY-LIFE (AGES 0 TO 5) AND CURRENT SES RESPECTIVELY. CELLULAR AGING OF MONOCYTES WAS MEASURED USING HORVATH'S DNA METHYLATION DERIVED MEASURE OF EPIGENETIC AGE ACCELERATION. RESULTS INDICATED THAT SOCIOECONOMIC DISADVANTAGE DURING EARLY-LIFE, BUT NOT LATER IN LIFE, WAS ASSOCIATED WITH ACCELERATED EPIGENETIC AGING OF MONOCYTES. NO EARLY-LIFE SES BY CURRENT SES INTERACTION WAS DETECTED, SUGGESTING THAT SOCIOECONOMIC MOBILITY IS UNRELATED TO EPIGENETIC AGE ACCELERATION. IN PATH ANALYSES, NEITHER CURRENT HEALTH BEHAVIORS NOR CURRENT DEPRESSIVE SYMPTOMS EMERGED AS MEDIATORS OF THE EARLY-LIFE SES EFFECT. THESE FINDINGS SUGGEST SOCIOECONOMIC DISADVANTAGE IN EARLY-LIFE IS INDEPENDENTLY PREDICTIVE OF CELLULAR AGING OF IMMUNE CELLS, WITH POTENTIAL IMPLICATIONS FOR AGING-RELATED DISEASES LATER IN LIFE.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
5 5747  37 SOCIAL ADVERSITY AND EPIGENETIC AGING: A MULTI-COHORT STUDY ON SOCIOECONOMIC DIFFERENCES IN PERIPHERAL BLOOD DNA METHYLATION. LOW SOCIOECONOMIC STATUS (SES) IS ASSOCIATED WITH EARLIER ONSET OF AGE-RELATED CHRONIC CONDITIONS AND REDUCED LIFE-EXPECTANCY, BUT THE UNDERLYING BIOMOLECULAR MECHANISMS REMAIN UNCLEAR. EVIDENCE OF DNA-METHYLATION DIFFERENCES BY SES SUGGESTS A POSSIBLE ASSOCIATION OF SES WITH EPIGENETIC AGE ACCELERATION (AA). WE INVESTIGATED THE ASSOCIATION OF SES WITH AA IN MORE THAN 5,000 INDIVIDUALS BELONGING TO THREE INDEPENDENT PROSPECTIVE COHORTS FROM ITALY, AUSTRALIA, AND IRELAND. LOW SES WAS ASSOCIATED WITH GREATER AA (BETA = 0.99 YEARS; 95% CI 0.39,1.59; P = 0.002; COMPARING EXTREME CATEGORIES). THE RESULTS WERE CONSISTENT ACROSS DIFFERENT SES INDICATORS. THE ASSOCIATIONS WERE ONLY PARTIALLY MODULATED BY THE UNHEALTHY LIFESTYLE HABITS OF INDIVIDUALS WITH LOWER SES. INDIVIDUALS WHO EXPERIENCED LIFE-COURSE SES IMPROVEMENT HAD INTERMEDIATE AA COMPARED TO EXTREME SES CATEGORIES, SUGGESTING REVERSIBILITY OF THE EFFECT AND SUPPORTING THE RELATIVE IMPORTANCE OF THE EARLY CHILDHOOD SOCIAL ENVIRONMENT. SOCIOECONOMIC ADVERSITY IS ASSOCIATED WITH ACCELERATED EPIGENETIC AGING, IMPLICATING BIOMOLECULAR MECHANISMS THAT MAY LINK SES TO AGE-RELATED DISEASES AND LONGEVITY.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
6 2485  30 EPIGENETIC-BASED AGE ACCELERATION IN A REPRESENTATIVE SAMPLE OF OLDER AMERICANS: ASSOCIATIONS WITH AGING-RELATED MORBIDITY AND MORTALITY. BIOMARKERS DEVELOPED FROM DNA METHYLATION (DNAM) DATA ARE OF GROWING INTEREST AS PREDICTORS OF HEALTH OUTCOMES AND MORTALITY IN OLDER POPULATIONS. HOWEVER, IT IS UNKNOWN HOW EPIGENETIC AGING FITS WITHIN THE CONTEXT OF KNOWN SOCIOECONOMIC AND BEHAVIORAL ASSOCIATIONS WITH AGING-RELATED HEALTH OUTCOMES IN A LARGE, POPULATION-BASED, AND DIVERSE SAMPLE. THIS STUDY USES DATA FROM A REPRESENTATIVE, PANEL STUDY OF US OLDER ADULTS TO EXAMINE THE RELATIONSHIP BETWEEN DNAM-BASED AGE ACCELERATION MEASURES IN THE PREDICTION OF CROSS-SECTIONAL AND LONGITUDINAL HEALTH OUTCOMES AND MORTALITY. WE EXAMINE WHETHER RECENT IMPROVEMENTS TO THESE SCORES, USING PRINCIPAL COMPONENT (PC)-BASED MEASURES DESIGNED TO REMOVE SOME OF THE TECHNICAL NOISE AND UNRELIABILITY IN MEASUREMENT, IMPROVE THE PREDICTIVE CAPABILITY OF THESE MEASURES. WE ALSO EXAMINE HOW WELL DNAM-BASED MEASURES PERFORM AGAINST WELL-KNOWN PREDICTORS OF HEALTH OUTCOMES SUCH AS DEMOGRAPHICS, SES, AND HEALTH BEHAVIORS. IN OUR SAMPLE, AGE ACCELERATION CALCULATED USING "SECOND AND THIRD GENERATION CLOCKS," PHENOAGE, GRIMAGE, AND DUNEDINPACE, IS CONSISTENTLY A SIGNIFICANT PREDICTOR OF HEALTH OUTCOMES INCLUDING CROSS-SECTIONAL COGNITIVE DYSFUNCTION, FUNCTIONAL LIMITATIONS AND CHRONIC CONDITIONS ASSESSED 2 Y AFTER DNAM MEASUREMENT, AND 4-Y MORTALITY. PC-BASED EPIGENETIC AGE ACCELERATION MEASURES DO NOT SIGNIFICANTLY CHANGE THE RELATIONSHIP OF DNAM-BASED AGE ACCELERATION MEASURES TO HEALTH OUTCOMES OR MORTALITY COMPARED TO EARLIER VERSIONS OF THESE MEASURES. WHILE THE USEFULNESS OF DNAM-BASED AGE ACCELERATION AS A PREDICTOR OF LATER LIFE HEALTH OUTCOMES IS QUITE CLEAR, OTHER FACTORS SUCH AS DEMOGRAPHICS, SES, MENTAL HEALTH, AND HEALTH BEHAVIORS REMAIN EQUALLY, IF NOT MORE ROBUST, PREDICTORS OF LATER LIFE OUTCOMES.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
7 3914  38 LIFETIME STRESS ACCELERATES EPIGENETIC AGING IN AN URBAN, AFRICAN AMERICAN COHORT: RELEVANCE OF GLUCOCORTICOID SIGNALING. BACKGROUND: CHRONIC PSYCHOLOGICAL STRESS IS ASSOCIATED WITH ACCELERATED AGING AND INCREASED RISK FOR AGING-RELATED DISEASES, BUT THE UNDERLYING MOLECULAR MECHANISMS ARE UNCLEAR. RESULTS: WE EXAMINED THE EFFECT OF LIFETIME STRESSORS ON A DNA METHYLATION-BASED AGE PREDICTOR, EPIGENETIC CLOCK. AFTER CONTROLLING FOR BLOOD CELL-TYPE COMPOSITION AND LIFESTYLE PARAMETERS, CUMULATIVE LIFETIME STRESS, BUT NOT CHILDHOOD MALTREATMENT OR CURRENT STRESS ALONE, PREDICTED ACCELERATED EPIGENETIC AGING IN AN URBAN, AFRICAN AMERICAN COHORT (N = 392). THIS EFFECT WAS PRIMARILY DRIVEN BY PERSONAL LIFE STRESSORS, WAS MORE PRONOUNCED WITH ADVANCING AGE, AND WAS BLUNTED IN INDIVIDUALS WITH HIGHER CHILDHOOD ABUSE EXPOSURE. HYPOTHESIZING THAT THESE EPIGENETIC EFFECTS COULD BE MEDIATED BY GLUCOCORTICOID SIGNALING, WE FOUND THAT A HIGH NUMBER (N = 85) OF EPIGENETIC CLOCK CPG SITES WERE LOCATED WITHIN GLUCOCORTICOID RESPONSE ELEMENTS. WE FURTHER EXAMINED THE FUNCTIONAL EFFECTS OF GLUCOCORTICOIDS ON EPIGENETIC CLOCK CPGS IN AN INDEPENDENT SAMPLE WITH GENOME-WIDE DNA METHYLATION (N = 124) AND GENE EXPRESSION DATA (N = 297) BEFORE AND AFTER EXPOSURE TO THE GLUCOCORTICOID RECEPTOR AGONIST DEXAMETHASONE. DEXAMETHASONE INDUCED DYNAMIC CHANGES IN METHYLATION IN 31.2 % (110/353) OF THESE CPGS AND TRANSCRIPTION IN 81.7 % (139/170) OF GENES NEIGHBORING EPIGENETIC CLOCK CPGS. DISEASE ENRICHMENT ANALYSIS OF THESE DEXAMETHASONE-REGULATED GENES SHOWED ENRICHED ASSOCIATION FOR AGING-RELATED DISEASES, INCLUDING CORONARY ARTERY DISEASE, ARTERIOSCLEROSIS, AND LEUKEMIAS. CONCLUSIONS: CUMULATIVE LIFETIME STRESS MAY ACCELERATE EPIGENETIC AGING, AN EFFECT THAT COULD BE DRIVEN BY GLUCOCORTICOID-INDUCED EPIGENETIC CHANGES. THESE FINDINGS CONTRIBUTE TO OUR UNDERSTANDING OF MECHANISMS LINKING CHRONIC STRESS WITH ACCELERATED AGING AND HEIGHTENED DISEASE RISK.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
8 1776  37 ECONOMIC HARDSHIP AND BIOLOGICAL WEATHERING: THE EPIGENETICS OF AGING IN A U.S. SAMPLE OF BLACK WOMEN. BACKGROUND: PAST RESEARCH HAS LINKED LOW SOCIO-ECONOMIC STATUS (SES) TO INFLAMMATION, METABOLIC DYSREGULATION, AND VARIOUS CHRONIC AND AGE-RELATED DISEASES SUCH AS TYPE 2 DIABETES, CORONARY HEART DISEASE, STROKE, AND DEMENTIA. THESE STUDIES SUGGEST THAT THE CHALLENGES AND ADVERSITIES ASSOCIATED WITH LOW SES MAY RESULT IN PREMATURE AGING AND INCREASED RISK OF MORBIDITY AND MORTALITY. OBJECTIVE: BUILDING UPON THIS RESEARCH, THE PRESENT STUDY INVESTIGATES VARIOUS AVENUES WHEREBY LOW INCOME MIGHT ACCELERATE BIOLOGICAL AGING. METHODS: STRUCTURAL EQUATION MODELING AND LONGITUDINAL DATA FROM A SAMPLE OF 100 BLACK, MIDDLE-AGED WOMEN RESIDING IN THE UNITED STATES WAS USED TO INVESTIGATE THE EFFECT OF INCOME ON A RECENTLY DEVELOPED EPIGENETIC MEASURE OF BIOLOGICAL AGING. THIS MEASURE CAN BE USED AS A "BIOLOGICAL CLOCK" TO ASSESS, AT ANY POINT DURING ADULTHOOD, THE EXTENT TO WHICH AN INDIVIDUAL IS EXPERIENCING ACCELERATED OR DECELERATED BIOLOGICAL AGING. RESULTS: LOW INCOME DISPLAYED A ROBUST ASSOCIATION WITH ACCELERATED AGING THAT WAS UNAFFECTED AFTER CONTROLLING FOR OTHER SES-RELATED FACTORS SUCH AS EDUCATION, MARITAL STATUS, AND CHILDHOOD ADVERSITY. FURTHER, OUR ANALYSES INDICATED THAT THE ASSOCIATION BETWEEN INCOME AND BIOLOGICAL AGING WAS NOT EXPLAINED BY HEALTH-RELATED BEHAVIORS SUCH AS DIET, EXERCISE, SMOKING, ALCOHOL CONSUMPTION, OR HAVING HEALTH INSURANCE. RATHER, IN LARGE MEASURE, IT WAS FINANCIAL PRESSURE (DIFFICULTY PAYING BILLS, BUYING NECESSITIES, OR MEETING DAILY EXPENSES) THAT ACCOUNTED FOR THE ASSOCIATION BETWEEN LOW INCOME AND ACCELERATED AGING. CONCLUSIONS: THESE FINDINGS SUPPORT THE VIEW THAT CHRONIC FINANCIAL PRESSURES ASSOCIATED WITH LOW INCOME EXERT A WEATHERING EFFECT THAT RESULTS IN PREMATURE AGING.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
9 4912  47 PAIN INTERFERENCE MEDIATES THE ASSOCIATION BETWEEN EPIGENETIC AGING AND GRIP STRENGTH IN MIDDLE TO OLDER AGED MALES AND FEMALES WITH CHRONIC PAIN. INTRODUCTION: CHRONIC PAIN IS ONE OF THE LEADING CAUSES OF DISABILITY THAT MAY ACCELERATE BIOLOGICAL AGING AND REDUCE PHYSICAL FUNCTION. EPIGENETIC CLOCKS PROVIDE AN ESTIMATE OF HOW THE SYSTEM AGES AND CAN PREDICT HEALTH OUTCOMES SUCH AS PHYSICAL FUNCTION. PHYSICAL FUNCTION DECLINES MAY BE ATTRIBUTED TO DECREASES IN MUSCLE QUALITY DUE TO DISUSE THAT CAN BE MEASURED QUICKLY AND NONINVASIVELY USING GRIP STRENGTH. THE PURPOSE OF THIS STUDY WAS TO EXPLORE THE ASSOCIATIONS AMONG SELF-REPORTED PAIN, GRIP STRENGTH, AND EPIGENETIC AGING IN THOSE WITH CHRONIC PAIN. METHODS: PARTICIPANTS (57.91 +/- 8.04 YEARS) COMPLETED PAIN QUESTIONNAIRES, A BLOOD DRAW AND HAND GRIP STRENGTH TASK. WE USED AN EPIGENETIC CLOCK PREVIOUSLY ASSOCIATED WITH KNEE PAIN (DNAMGRIMAGE), AND USED THE SUBSEQUENT DIFFERENCE OF PREDICTED EPIGENETIC AGE FROM CHRONOLOGICAL AGE (DNAMGRIMAGE-DIFFERENCE). RESULTS: EXPLORATORY PATHWAY ANALYSES REVEALED THAT PAIN INTENSITY MEDIATED THE ASSOCIATION BETWEEN DNAMGRIMAGE-DIFFERENCE AND HANDGRIP STRENGTH IN MALES ONLY (BETA = -0.1115; CI [-0.2929, -0.0008]) AND PAIN INTERFERENCE MEDIATED THE ASSOCIATION BETWEEN DNAMGRIMAGE-DIFFERENCE AND HANDGRIP STRENGTH IN MALES BETA = -0.1401; CI [-0.3400, -0.0222]), AND FEMALES (BETA = -0.024; CI [-0.2918, -0.0020]). DISCUSSION: CHRONIC KNEE PAIN MAY ACCELERATE EPIGENETIC AGING PROCESSES THAT MAY INFLUENCE HANDGRIP STRENGTH IN OLDER AGE ADULTS. CHRONIC PAIN COULD BE A SYMPTOM OF THE AGING BODY THUS CONTRIBUTING TO DECLINES IN MUSCULOSKELETAL FUNCTION IN LATER LIFE.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10  175  28 ACCELERATED AGING WITH HIV BEGINS AT THE TIME OF INITIAL HIV INFECTION. LIVING WITH HIV INFECTION IS ASSOCIATED WITH EARLY ONSET OF AGING-RELATED CHRONIC CONDITIONS, SOMETIMES DESCRIBED AS ACCELERATED AGING. EPIGENETIC DNA METHYLATION PATTERNS CAN EVALUATE ACCELERATION OF BIOLOGICAL AGE RELATIVE TO CHRONOLOGICAL AGE. THE IMPACT OF INITIAL HIV INFECTION ON FIVE EPIGENETIC MEASURES OF AGING WAS EXAMINED BEFORE AND APPROXIMATELY 3 YEARS AFTER HIV INFECTION IN THE SAME INDIVIDUALS (N=102). SIGNIFICANT EPIGENETIC AGE ACCELERATION (MEDIAN 1.9-4.8 YEARS) AND ESTIMATED TELOMERE LENGTH SHORTENING (ALL P</= 0.001) WERE OBSERVED FROM PRE-TO POST-HIV INFECTION, AND REMAINED SIGNIFICANT IN THREE EPIGENETIC MEASURES AFTER CONTROLLING FOR T CELL CHANGES. NO ACCELERATION WAS SEEN IN AGE- AND TIME INTERVAL-MATCHED HIV-UNINFECTED CONTROLS. CHANGES IN GENOME-WIDE CO-METHYLATION CLUSTERS WERE ALSO SIGNIFICANTLY ASSOCIATED WITH INITIAL HIV INFECTION (P</= 2.0 X 10(-4)). THESE LONGITUDINAL OBSERVATIONS CLEARLY DEMONSTRATE AN EARLY AND SUBSTANTIAL IMPACT OF HIV INFECTION ON THE EPIGENETIC AGING PROCESS, AND SUGGEST A ROLE FOR HIV ITSELF IN THE EARLIER ONSET OF CLINICAL AGING.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
11 3391  38 HORMETIC ASSOCIATION BETWEEN PERCEIVED STRESS AND HUMAN EPIGENETIC AGING BASED ON RESILIENCE CAPACITY. CHRONIC STRESS IS ASSOCIATED WITH DELETERIOUS HEALTH OUTCOMES AND MORTALITY RISK. A POTENTIAL MECHANISM BY WHICH STRESS AFFECTS HEALTHSPAN AND LIFESPAN IS ACCELERATION OF CELLULAR AGING. BIOLOGIC AGE PREDICTION MODELS, TERMED EPIGENETIC CLOCKS, HAVE BEEN DEVELOPED TO ESTIMATE BIOLOGIC AGE DIFFERENCES AMONG PEOPLE WITH THE SAME CHRONOLOGIC AGE. THIS STUDY EVALUATES THE SIMULTANEOUS IMPACT OF PERCEIVED CHRONIC STRESS AND RESILIENCE ON GRIM AGE ACCELERATION. THE PERCEIVED STRESS SCORE (PSS) AND CONNOR-DAVIDSON RESILIENCE SCALE (CD-RISC) WERE USED TO MEASURE CHRONIC STRESS AND RESILIENCE, RESPECTIVELY. DNA WAS EXTRACTED FROM WHOLE BLOOD AND ANALYZED USING THE METHYLATIONEPIC BEADCHIP. GRIMAGE ESTIMATES WERE CALCULATED USING THE METHYLATION AGE CALCULATOR. FORTY-SEVEN BUSINESS EXECUTIVES WERE CATEGORIZED BY LEVELS OF HIGH OR LOW STRESS AND RESILIENCE SCORES. COMPARED TO PARTICIPANTS WITH LOW STRESS AND HIGH RESILIENCE, THOSE WITH LOW STRESS AND LOW RESILIENCE DEMONSTRATED THE STRONGEST ASSOCIATION WITH GRIM AGE ACCELERATION (P = 0.044), AFTER CONTROLLING FOR AGE AND ESTIMATED CELLULAR PROPORTIONS. INTERESTINGLY, AMONG PARTICIPANTS WITH LOW RESILIENCE, THOSE WITH HIGH PERCEIVED STRESS HAD A WEAKER ASSOCIATION WITH GRIM AGE ACCELERATION THAN PARTICIPANTS WITH LOW PERCEIVED STRESS. HOWEVER, AMONG PARTICIPANTS WITH HIGH RESILIENCE, LOW PERCEIVED STRESS HAD A WEAKER ASSOCIATION WITH GRIM AGE ACCELERATION THAN HIGH PERCEIVED STRESS. OUR FINDINGS SUGGEST THAT THE IMPACT OF PERCEIVED STRESS ON EPIGENETIC AGE ACCELERATION MAY DIFFER BASED ON RESILIENCE CAPACITY, WITH A POTENTIAL PARADOXICAL BENEFICIAL EFFECT AMONG THOSE WITH LOW RESILIENCE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
12 3911  35 LIFE-COURSE SOCIOECONOMIC STATUS AND DNA METHYLATION OF GENES REGULATING INFLAMMATION. BACKGROUND: IN HUMANS, LOW SOCIOECONOMIC STATUS (SES) ACROSS THE LIFE COURSE IS ASSOCIATED WITH GREATER DIURNAL CORTISOL PRODUCTION, INCREASED INFLAMMATORY ACTIVITY AND HIGHER CIRCULATING ANTIBODIES FOR SEVERAL PATHOGENS, ALL SUGGESTING A DAMPENED IMMUNE RESPONSE. RECENT EVIDENCE SUGGESTS THAT DNA METHYLATION OF PRO-INFLAMMATORY GENES MAY BE IMPLICATED IN THE BIOLOGICAL EMBEDDING OF THE SOCIAL ENVIRONMENT. METHODS: THE PRESENT STUDY EXAMINES THE ASSOCIATION BETWEEN LIFE-COURSE SES AND DNA METHYLATION OF CANDIDATE GENES, SELECTED ON THE BASIS OF THEIR INVOLVEMENT IN SES-RELATED INFLAMMATION, IN THE CONTEXT OF A GENOME-WIDE METHYLATION STUDY. PARTICIPANTS WERE 857 HEALTHY INDIVIDUALS SAMPLED FROM THE EPIC ITALY PROSPECTIVE COHORT STUDY. RESULTS: INDICATORS OF SES WERE ASSOCIATED WITH DNA METHYLATION OF GENES INVOLVED IN INFLAMMATION. NFATC1, IN PARTICULAR, WAS CONSISTENTLY FOUND TO BE LESS METHYLATED IN INDIVIDUALS WITH LOW VS HIGH SES, IN A DOSE-DEPENDENT MANNER. IL1A, GPR132 AND GENES BELONGING TO THE MAPK FAMILY WERE ALSO LESS METHYLATED AMONG INDIVIDUALS WITH LOW SES. IN ADDITION, ASSOCIATIONS WERE FOUND BETWEEN SES AND CXCL2 AND PTGS2, BUT THESE GENES WERE CONSISTENTLY MORE METHYLATED AMONG LOW SES INDIVIDUALS. CONCLUSIONS: OUR FINDINGS SUPPORT THE HYPOTHESIS THAT THE SOCIAL ENVIRONMENT LEAVES AN EPIGENETIC SIGNATURE IN CELLS. ALTHOUGH THE FUNCTIONAL SIGNIFICANCE OF SES-RELATED DNA METHYLATION IS STILL UNCLEAR, WE HYPOTHESIZE THAT IT MAY LINK SES TO CHRONIC DISEASE RISK.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13 1962  50 EPIGENETIC AGING IS ASSOCIATED WITH CLINICAL AND EXPERIMENTAL PAIN IN COMMUNITY-DWELLING OLDER ADULTS. GERONTOLOGICAL RESEARCH REVEALS CONSIDERABLE INTERINDIVIDUAL VARIABILITY IN AGING PHENOTYPES, WHICH HAS MOTIVATED RESEARCH EFFORTS TO IDENTIFY "AGING BIOMARKERS." AGING BIOMARKERS ARE USED TO CALCULATE BIOLOGICAL AGE, WHICH ARE BETTER PREDICTORS OF DISEASE RISK AND RESIDUAL LIFESPAN WHEN COMPARED TO CHRONOLOGICAL AGE ALONE. EMERGING EVIDENCE USING THE EPIGENETIC CLOCK AS AN AGING BIOMARKER SUPPORTS HIGHLY RELIABLE INDIVIDUALIZED PREDICTIONS ABOUT FUTURE HEALTH. THIS STUDY AIMED TO DETERMINE WHETHER AN EPIGENETIC AGING BIOMARKER WAS ASSOCIATED WITH CHRONIC PAIN IN OLDER ADULTS (60-83 YEARS OLD). A SUBSET OF PARTICIPANTS (N = 29) IN THE NEUROMODULATORY EXAMINATION OF PAIN AND MOBILITY ACROSS THE LIFESPAN STUDY UNDERWENT A BLOOD DRAW, DEMOGRAPHIC, PSYCHOLOGICAL, COGNITIVE, AND PAIN ASSESSMENTS. WE ESTIMATED HORVATH'S EPIGENETIC CLOCK AND CALCULATED THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE THAT HAS BEEN PREVIOUSLY REPORTED TO PREDICT OVERALL MORTALITY RISK. OLDER INDIVIDUALS WITHOUT CHRONIC PAIN (N = 9) HAD SIGNIFICANTLY "YOUNGER" EPIGENETIC AGE COMPARED TO THOSE WITH CHRONIC PAIN (N = 20, P < 0.05). OLDER EPIGENETIC AGE WAS ASSOCIATED WITH GREATER PAIN DURING DAILY ACTIVITIES (R = 0.494, P = 0.010) AND ANATOMICAL PAIN SITES (R = 0.741, P < 0.001) BUT NOT PAIN FREQUENCY/DURATION. AN OLDER EPIGENETIC AGE WAS ALSO ASSOCIATED WITH HIGHER VIBRATORY DETECTION THRESHOLDS (R = 0.490, P = 0.021), HEAT PAIN THRESHOLDS (R = -0.478, P = 0.028), AND PRESSURE PAIN THRESHOLDS AT THE TRAPEZIUS (R = -0.571, P = 0.006) BUT NOT THERMAL DETECTION, PRESSURE PAIN AT THE QUADRICEPS OR PAIN INHIBITION (P'S > 0.05). EPIGENETIC AGING WAS ASSOCIATED WITH GREATER EMOTIONAL STABILITY (R = -0.461, P = 0.027), CONSCIENTIOUSNESS (R = -0.549, P = 0.007), AND LOWER EXTRAVERSION (R = 0.414, P = 0.049) BUT NOT DEPRESSION OR AFFECT (P'S > 0.05). EPIGENETIC AGING WAS ALSO ASSOCIATED WITH LOWER EPISODIC (R = -0.698, P = 0.001) AND WORKING MEMORY (R = -0.760, P < 0.001). OUR FINDINGS SUGGEST THAT CHRONIC PAIN IS ASSOCIATED WITH ACCELERATED EPIGENETIC AGING IN HEALTHY, COMMUNITY-DWELLING OLDER INDIVIDUALS, AND FUTURE STUDIES WITH LARGER SAMPLES ARE NEEDED TO CONFIRM OUR FINDINGS. AN AGING BIOMARKER SUCH AS THE EPIGENETIC CLOCK MAY HELP IDENTIFY PEOPLE WITH CHRONIC PAIN AT GREATER RISK OF FUNCTIONAL DECLINE AND POORER HEALTH OUTCOMES.	2019	

14  177  26 ACCELERATED EPIGENETIC AGING AND INFLAMMATORY/IMMUNOLOGICAL PROFILE (IPAGE) IN PATIENTS WITH CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS DEFINED BY A REDUCED ESTIMATED GLOMERULAR FILTRATION RATE (EGFR). THIS FAILURE CAN BE RELATED TO A PHENOTYPE OF ACCELERATED AGING. IN THIS WORK, WE CONSIDERED 76 PATIENTS WITH END-STAGE RENAL DISEASE (ESRD) AND 83 HEALTHY CONTROLS. WE CONCOMITANTLY EVALUATED FOR THE FIRST TIME TWO MEASURES THAT CAN BE INFORMATIVE OF THE RATE OF AGING, I.E., WHOLE BLOOD DNA METHYLATION USING THE ILLUMINA INFINIUM EPIC ARRAY AND PLASMA LEVELS OF A SELECTION OF INFLAMMATORY/IMMUNOLOGICAL PROTEINS USING MULTIPLEX IMMUNOASSAYS. FIRST OF ALL, WE DEMONSTRATED ACCELERATED AGING IN TERMS OF THE MOST COMMON EPIGENETIC AGE ESTIMATORS IN CKD PATIENTS. MOREOVER, WE DEVELOPED A NEW CLOCK/PREDICTOR OF AGE BASED ON THE INFLAMMATORY/IMMUNOLOGICAL PROFILE (IPAGE) AND IDENTIFIED THE INFLAMMATORY/IMMUNOLOGICAL BIOMARKERS DIFFERENTIALLY EXPRESSED BETWEEN CASES AND CONTROLS. IPAGE APPEARED TO BE MORE SENSITIVE THAN EPIGENETIC CLOCKS IN QUANTIFYING THE ACCELERATED AGING PHENOTYPE OF ESRD PATIENTS. INTERESTINGLY, WE DID NOT FIND ANY CORRELATION BETWEEN THE AGE ACCELERATION EVALUATED ACCORDING TO THE EPIGENETIC CLOCKS AND IPAGE IN EITHER THE ESRD GROUP OR THE CONTROL GROUP. ON THE WHOLE, OUR DATA SHOW A CONSISTENT ACCELERATED AGING PHENOTYPE IN ESRD PATIENTS, WHICH IS BETTER APPRECIATED BY QUANTIFYING THE UNDERLYING INFLAMMATORY PROCESSES (INFLAMMAGING) BY IPAGE THAN BY USING EPIGENETIC CLOCKS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
15 6751  19 WHY ARE PEOPLE WITH HIV CONSIDERED "OLDER ADULTS" IN THEIR FIFTIES? ONE IN SIX NEW HIV DIAGNOSES IN EUROPE OCCUR AMONG PEOPLE OVER 50 YEARS OF AGE. AS IN THE GENERAL POPULATION, THE AGING PROCESS IS NOT HOMOGENEOUS AMONG OLDER ADULTS WITH HIV, AND SOME OF THEM EXHIBIT IMPAIRED PHYSICAL FUNCTION, HIGHER FRAILTY AND MORE FREQUENT GERIATRIC SYNDROMES. THESE ILLNESS REFLECT A HIGHER BIOLOGICAL AGE INDEPENDENTLY OF THEIR CHRONOLOGICAL AGE. AFTER STARTING ANTIRRETROVIRAL TREATMENT, PEOPLE LIVING WITH HIV (PLWH) OLDER THAN 50 EXHIBIT A POORER IMMUNOLOGICAL RECOVERY THAN YOUNGER PLWH. MOREOVER, OLDER ADULTS WITH HIV PRESENT EARLY ONSET OF COMORBIDITIES AND FUNCTIONAL IMPAIRMENT CAUSED BY PERSISTENT AND CHRONIC ACTIVATION OF THE IMMUNE SYSTEM, WHICH LEADS TO IMMUNE EXHAUSTION AND ACCELERATED IMMUNOSENESCENCE DESPITE OPTIMAL SUPPRESSION OF HIV REPLICATION. THE EVIDENCE OF POORER IMMUNOLOGICAL RESPONSE TO ARV, LINKED WITH EARLY IMMUNOSENESCENCE IN PLWH AND ITS PREMATURELY DELETERIOUS EFFECT IN PHYSIOLOGICAL FUNCTIONS AND ITS CLINICAL CONSEQUENCES, ARE THE BASIS TO ACCEPT THE CUT-OFF OF 50 YEARS OF AGE TO DEFINE AN "OLDER ADULT WITH HIV".	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
16 1553  42 DNA METHYLATION LEVELS ASSOCIATED WITH RACE AND CHILDHOOD ASTHMA SEVERITY. OBJECTIVE: ASTHMA IS A COMMON CHRONIC CHILDHOOD DISEASE WORLDWIDE. SOCIOECONOMIC STATUS, GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS CONTRIBUTE TO ITS INCIDENCE AND SEVERITY. A DISPROPORTIONATE NUMBER OF CHILDREN WITH ASTHMA ARE ECONOMICALLY DISADVANTAGED AND LIVE IN SUBSTANDARD HOUSING WITH POTENTIAL INDOOR ENVIRONMENTAL EXPOSURES SUCH AS COCKROACHES, DUST MITES, RODENTS AND MOLDS. THESE EXPOSURES MAY MANIFEST THROUGH EPIGENETIC MECHANISMS THAT CAN LEAD TO CHANGES IN RELEVANT GENE EXPRESSION. WE EXAMINED THE ASSOCIATION OF GLOBAL DNA METHYLATION LEVELS WITH SOCIOECONOMIC STATUS, ASTHMA SEVERITY AND RACE/ETHNICITY. METHODS: WE MEASURED GLOBAL DNA METHYLATION IN PERIPHERAL BLOOD OF CHILDREN WITH ASTHMA ENROLLED IN THE KANSAS CITY SAFE AND HEALTHY HOMES PROGRAM. INCLUSION CRITERIA INCLUDED RESIDING IN THE SAME HOME FOR A MINIMUM OF 4 DAYS PER WEEK AND TOTAL FAMILY INCOME OF LESS THAN 80% OF THE KANSAS CITY MEDIAN FAMILY INCOME. DNA METHYLATION LEVELS WERE QUANTIFIED BY AN IMMUNOASSAY THAT ASSESSED THE PERCENTAGE OF 5-METHYLCYTOSINE. RESULTS: OUR RESULTS INDICATE THAT OVERALL, AFRICAN AMERICAN CHILDREN HAD HIGHER LEVELS OF GLOBAL DNA METHYLATION THAN CHILDREN OF OTHER RACES/ETHNICITIES (P = 0.029). THIS DIFFERENCE WAS MORE PRONOUNCED WHEN SOCIOECONOMIC STATUS AND ASTHMA SEVERITY WERE COUPLED WITH RACE/ETHNICITY (P = 0.042) WHERE LOW-INCOME, AFRICAN AMERICAN CHILDREN WITH PERSISTENT ASTHMA HAD SIGNIFICANTLY ELEVATED METHYLATION LEVELS RELATIVE TO OTHER RACES/ETHNICITIES IN THE SAME CONTEXT (P = 0.006, HEDGES G = 1.14). CONCLUSION: OUR STUDY DEMONSTRATES A SIGNIFICANT INTERACTION EFFECT AMONG GLOBAL DNA METHYLATION LEVELS, ASTHMA SEVERITY, RACE/ETHNICITY, AND SOCIOECONOMIC STATUS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
17  381  35 AN EPIGENOME-WIDE ASSOCIATION STUDY OF EARLY-ONSET MAJOR DEPRESSION IN MONOZYGOTIC TWINS. MAJOR DEPRESSION (MD) IS A DEBILITATING MENTAL HEALTH CONDITION WITH PEAK PREVALENCE OCCURRING EARLY IN LIFE. GENOME-WIDE EXAMINATION OF DNA METHYLATION (DNAM) OFFERS AN ATTRACTIVE COMPLEMENT TO STUDIES OF ALLELIC RISK GIVEN IT CAN REFLECT THE COMBINED INFLUENCE OF GENES AND ENVIRONMENT. THE CURRENT STUDY USED MONOZYGOTIC TWINS TO IDENTIFY DIFFERENTIALLY AND VARIABLY METHYLATED REGIONS OF THE GENOME THAT DISTINGUISH TWINS WITH AND WITHOUT A LIFETIME HISTORY OF EARLY-ONSET MD. THE SAMPLE INCLUDED 150 CAUCASIAN MONOZYGOTIC TWINS BETWEEN THE AGES OF 15 AND 20 (73% FEMALE; MAGE = 17.52 SD = 1.28) WHO WERE ASSESSED DURING A DEVELOPMENTAL STAGE CHARACTERIZED BY RELATIVELY DISTINCT NEUROPHYSIOLOGICAL CHANGES. ALL TWINS WERE GENERALLY HEALTHY AND CURRENTLY FREE OF MEDICATIONS WITH PSYCHOTROPIC EFFECTS. DNAM WAS MEASURED IN PERIPHERAL BLOOD CELLS USING THE INFINIUM HUMAN BEADCHIP 450 K ARRAY. MD ASSOCIATIONS WITH EARLY-ONSET MD WERE DETECTED AT 760 DIFFERENTIALLY AND VARIABLY METHYLATED PROBES/REGIONS THAT MAPPED TO 428 GENES. GENES AND GENOMIC REGIONS INVOLVED NEURAL CIRCUITRY FORMATION, PROJECTION, FUNCTIONING, AND PLASTICITY. GENE ENRICHMENT ANALYSES IMPLICATED GENES RELATED TO NEURON STRUCTURES AND NEURODEVELOPMENTAL PROCESSES INCLUDING CELL-CELL ADHESION GENES (E.G., PCDHA GENES). GENES PREVIOUSLY IMPLICATED IN MOOD AND PSYCHIATRIC DISORDERS AS WELL AS CHRONIC STRESS (E.G., NRG3) ALSO WERE IDENTIFIED. DNAM REGIONS ASSOCIATED WITH EARLY-ONSET MD WERE FOUND TO OVERLAP GENETIC LOCI IDENTIFIED IN THE LATEST PSYCHIATRIC GENOMICS CONSORTIUM META-ANALYSIS OF DEPRESSION. UNDERSTANDING THE TIME COURSE OF EPIGENETIC INFLUENCES DURING EMERGING ADULTHOOD MAY CLARIFY DEVELOPMENTAL PHASES WHERE CHANGES IN THE DNA METHYLOME MAY MODULATE INDIVIDUAL DIFFERENCES IN MD RISK.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
18 1537  27 DNA METHYLATION IN ADOLESCENTS WITH ANXIETY DISORDER: A LONGITUDINAL STUDY. ANXIETY DISORDERS (AD) TYPICALLY MANIFEST IN CHILDREN AND ADOLESCENTS AND MIGHT PERSIST INTO ADULTHOOD. HOWEVER, THERE ARE STILL FEW DATA CONCERNING EPIGENETIC MECHANISMS ASSOCIATED WITH ONSET, PERSISTENCE OR REMISSION OF AD OVER TIME. WE INVESTIGATED A COHORT OF ADOLESCENTS AND YOUNG ADULTS AT BASELINE (AGE; 13.19 +/- 2.38) AND AFTER 5 YEARS AND CLASSIFIED THEM ACCORDING TO THE AD DIAGNOSIS AND THEIR LONGITUDINAL TRAJECTORIES INTO 4 GROUPS: (1) TYPICALLY DEVELOPING COMPARISONS (TDC; CONTROL GROUP, N = 14); (2) INCIDENT (AD IN THE SECOND EVALUATION ONLY, N = 11); (3) PERSISTENT (AD IN BOTH EVALUATIONS, N = 14) AND (4) REMITTENT (AD IN THE FIRST EVALUATION ONLY, N = 8). DNA METHYLATION WAS EVALUATED WITH THE INFINIUM HUMANMETHYLATION450 BEADCHIP FROM SALIVA SAMPLES COLLECTED AT BOTH EVALUATIONS. GENE SET ENRICHMENT ANALYSIS WAS APPLIED TO CONSIDER BIOLOGICAL PATHWAYS. WE FOUND DECREASED DNA METHYLATION IN TDC GROUP WHILE THE CHRONIC CASES OF AD PRESENTED HYPERMETHYLATION IN CENTRAL NERVOUS SYSTEM DEVELOPMENT PATHWAYS. MOREOVER, WE SHOWED THAT THIS PERSISTENT GROUP ALSO PRESENTED HYPERMETHYLATION WHILE THE OTHER THREE GROUPS WERE ASSOCIATED WITH HYPOMETHYLATION IN NERVOUS SYSTEM DEVELOPMENT PATHWAY. INCIDENCE AND REMISSION GROUPS WERE ASSOCIATED WITH INCREASED AND DECREASED METHYLATION IN NEURON DEVELOPMENT PATHWAYS, RESPECTIVELY. LARGER STUDIES ARE LIKELY TO DETECT SPECIFIC GENES RELEVANT TO AD.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
19 1408  35 DIETARY INTAKE IS ASSOCIATED WITH RESPIRATORY HEALTH OUTCOMES AND DNA METHYLATION IN CHILDREN WITH ASTHMA. BACKGROUND: ASTHMA IS AN INCREASINGLY COMMON CHRONIC DISEASE AMONG CHILDREN, AND DATA POINT TOWARD A COMPLEX MECHANISM INVOLVING GENETIC, ENVIRONMENTAL AND EPIGENETIC FACTORS. EPIGENETIC MODIFICATIONS SUCH AS DNA HYPO- OR HYPER-METHYLATION HAVE BEEN SHOWN TO OCCUR IN RESPONSE TO ENVIRONMENTAL EXPOSURES INCLUDING DIETARY NUTRIENTS. METHODS: WITHIN THE CONTEXT OF THE ASTHMA RANDOMIZED TRIAL OF INDOOR WOOD SMOKE (ARTIS) STUDY, WE INVESTIGATED RELATIONSHIPS BETWEEN DIET, ASTHMA HEALTH MEASURES, AND DNA METHYLATION. ASTHMA HEALTH MEASURES INCLUDED A QUALITY OF LIFE INSTRUMENT, DIURNAL PEAK FLOW VARIABILITY (DPFV) AND FORCED EXPIRATORY VOLUME IN THE FIRST SECOND (FEV(1)). DIETARY INTAKE WAS ASSESSED WITH A FOOD FREQUENCY QUESTIONNAIRE. METHYLATION LEVELS OF LINE-1 REPETITIVE ELEMENT AND TWO PROMOTER CPG SITES FOR INTERFERON GAMMA (IFNGAMMA, -186 AND -54) FROM BUCCAL CELL DNA WERE MEASURED USING PYROSEQUENCING ASSAYS. RESULTS: DATA WERE COLLECTED ON 32 CHILDREN WITH ASTHMA LIVING IN WESTERN MONTANA WHO WERE RECRUITED TO THE ARTIS STUDY. SELENIUM AND SEVERAL METHYL DONOR DIETARY NUTRIENTS WERE POSITIVELY ASSOCIATED WITH THE ASTHMA QUALITY OF LIFE MEASURE. INTAKE OF METHYL DONATING NUTRIENTS INCLUDING FOLATE WAS POSITIVELY ASSOCIATED LINE-1 METHYLATION AND NEGATIVELY ASSOCIATED WITH IFNGAMMA CPG-186. HIGHER LEVELS OF LINE-1 METHYLATION WERE ASSOCIATED WITH GREATER DPFV. CONCLUSION: WE IDENTIFIED SEVERAL NUTRIENTS THAT WERE ASSOCIATED WITH IMPROVED QUALITY OF LIFE MEASURES AMONG CHILDREN WITH ASTHMA. THE IFNGAMMA PROMOTER CPG SITE -186 BUT NOT -54 WAS ASSOCIATED WITH THE INTAKE OF SELECTED DIETARY NUTRIENTS. HOWEVER, IN THIS SMALL POPULATION OF CHILDREN WITH ASTHMA, THE IFNGAMMA PROMOTER CPG SITES WERE NOT ASSOCIATED WITH RESPIRATORY HEALTH MEASURES SO IT REMAINS UNCLEAR THROUGH WHICH EPIGENETIC MECHANISM THESE NUTRIENTS ARE IMPACTING THE QUALITY OF LIFE MEASURE. THESE FINDINGS ADD TO THE EVIDENCE THAT DIETARY NUTRIENTS, PARTICULARLY FOODS CONTAINING METHYL DONORS, MAY BE IMPORTANT FOR EPIGENETIC REGULATION AS IT PERTAINS TO THE CONTROL OF ASTHMA. TRIAL REGISTRATION CLINCIALTRIALS.GOV NCT00807183. REGISTERED 10 DECEMBER 2008.	2017	
                                                                                                                                                                                                 
20 2047  25 EPIGENETIC CLOCKS MAY COME OUT OF RHYTHM-IMPLICATIONS FOR THE ESTIMATION OF CHRONOLOGICAL AGE IN FORENSIC CASEWORK. THERE IS A GROWING PERCEPTION THAT DNA METHYLATION MAY BE INFLUENCED BY EXOGENOUS AND ENDOGENOUS PARAMETERS. KNOWLEDGE OF THESE FACTORS IS OF GREAT RELEVANCE FOR THE INTERPRETATION OF DNA-METHYLATION DATA FOR THE ESTIMATION OF CHRONOLOGICAL AGE IN FORENSIC CASEWORK. WE PERFORMED A LITERATURE REVIEW TO IDENTIFY PARAMETERS, WHICH MIGHT BE OF RELEVANCE FOR THE PREDICTION OF CHRONOLOGICAL AGE BASED ON DNA METHYLATION. THE QUALITY OF AGE PREDICTIONS MIGHT PARTICULARLY BE INFLUENCED BY LIFETIME ADVERSITIES (CHRONIC STRESS, TRAUMA/POST-TRAUMATIC STRESS DISORDER (PTSD), VIOLENCE, LOW SOCIOECONOMIC STATUS/EDUCATION), CANCER, OBESITY AND RELATED DISEASES, INFECTIOUS DISEASES (ESPECIALLY HIV AND CYTOMEGALOVIRUS (CMV) INFECTIONS), SEX, ETHNICITY AND EXPOSURE TO TOXINS (ALCOHOL, SMOKING, AIR POLLUTION, PESTICIDES). SUCH FACTORS MAY ALTER THE DNA METHYLATION PATTERN AND MAY EXPLAIN THE PARTLY HIGH DEVIATIONS BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE IN SINGLE CASES (DESPITE OF LOW MEAN ABSOLUTE DEVIATIONS) THAT CAN ALSO BE OBSERVED WITH "EPIGENETIC CLOCKS" COMPRISING A HIGH NUMBER OF CPG SITES. SO FAR, ONLY FEW PUBLICATIONS DEALING WITH FORENSIC AGE ESTIMATION ADDRESS THESE CONFOUNDING FACTORS. FUTURE RESEARCH SHOULD FOCUS ON THE IDENTIFICATION OF FURTHER RELEVANT CONFOUNDING FACTORS AND THE DEVELOPMENT OF MODELS THAT ARE "ROBUST" AGAINST THE INFLUENCE OF SUCH BIOLOGICAL FACTORS BY SYSTEMATIC INVESTIGATIONS UNDER TARGETED INCLUSION OF DIVERSE AND DEFINED COHORTS.	2020