Racial discrimination during middle age predicts higher serum phosphorylated tau and neurofilament light chain levels a decade later: A study of aging black Americans.

INTRODUCTION: Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans. METHODS: The present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). We hypothesized that racial discrimination assessed during middle age would predict increases in these serum biomarkers as the participants aged into their 60s. RESULTS: Our findings indicate that exposure to various forms of racial discrimination during a person's 40s and early 50s predicts an 11-year increase in both serum p-tau181 and NfL. Racial discrimination was not associated with subsequent levels of GFAP. DISCUSSION: These findings suggest that racial discrimination in midlife may contribute to increased AD pathology and neurodegeneration later in life. HIGHLIGHTS: A 17-year longitudinal study of Black Americans. Assessments of change in serum p-tau181, neurofilament light, and glial fibrillary acidic protein. Exposure to racial discrimination during middle age predicted increases in p-tau181 and neurofilament light. Education was positively related to both p-tau181 and exposure to racial discrimination.

Childhood adversity predicts black young adults' DNA methylation-based accelerated aging: A dual pathway model.

We expand upon prior work (Gibbons et al., ) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes - deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., ), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).

Childhood adversity is linked to adult health among African Americans via adolescent weight gain and effects are genetically moderated.

Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.

Evaluating Observer Ratings: The Case of Measuring Neighborhood Disorder.

The purpose of this study is to evaluate the quality of observer ratings of neighborhood disorder using a many-facet Rasch model (MFRM). Our goal is to investigate observer severity and observer consistency. Observers trained in the use of a systematic social observation visited and rated residential neighborhoods. Data for this study are drawn from the Family and Community Health Study (FACHS). The FACHS sample consisted of 673 neighborhoods. Two observers, out of a total of 67 observers used for this study, rated each residential neighborhood. The results of this study suggested that there were statistically significant differences in observer severity, even after observer training, and that the ratings of observers are not consistent. Therefore, more or better observer training is necessary. In addition, the interaction effect between observer and item was significant, indicating significant variance in observer severity across at least one item.

MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for African American young adults.

Smoking has been shown to have a large, reliable, and rapid effect on demethylation of AHRR, particularly at cg05575921, suggesting that methylation may be used as an index of cigarette consumption. Because the availability of methyl donors may also influence the degree of demethylation in response to smoking, factors that affect the activity of methylene tetrahydrofolate reductase (MTHFR), a key regulator of methyl group availability, may be of interest. In the current investigation, we examined the extent to which individual differences in methylation of MTHFR moderated the association between smoking and demethylation at cg05575921 as well as at other loci on AHRR associated with a main effect of smoking. Using a discovery sample (AIM, N = 293), and a confirmatory sample (SHAPE, N = 368) of young adult African Americans, degree of methylation of loci in the first exon of MTHFR was associated with amplification of the association between smoking and AHRR demethylation at cg05575921. However, genetic variation at a commonly studied MTHFR variant, C677T, did not influence cg05575921 methylation. The significant interaction between MTHFR methylation and the smoking-induced response at cg05575921 suggests a role for individual differences in methyl cycle regulation in understanding the effects of cigarette consumption on genome wide DNA methylation.

Racial discrimination predicts depressive symptoms throughout adolescence among Black youth.

Experiences of racial discrimination are common among Black youth and predict worse mental health cross-sectionally and over time. Additional research is needed to address lingering questions regarding the direction of effect(s) underlying these patterns, differences in the magnitude of effects across adolescence, and gender differences. To address these gaps, the current study tested bidirectional linkages between racial discrimination and depressive symptoms at the between- (interpersonal) and within- (intrapersonal) level using 4 waves of data from 889 Black youth (54% female) from Georgia and Iowa. Participants reported experiences of racial discrimination and depressive symptoms at ages 10.6 years (Wave 1), 12.5 years (Wave 2), 15.7 years (Wave 3), and 18.8 years (Wave 4). The cross-lagged panel model (CLPM) was used to examine between-person associations over time, and the random intercept cross-lagged panel model (RI-CLPM) was used to examine within-person associations over time. Results were consistent across models, revealing significant concurrent associations between racial discrimination and depressive symptoms, significant lagged effects from racial discrimination to depressive symptoms, and no significant lagged effects from depressive symptoms to racial discrimination. Effects did not differ across adolescence, and there were few gender differences in the degree of association between racial discrimination and depressive symptoms. Findings provide rigorous evidence that experiencing greater racial discrimination is associated with increases in depressive symptoms throughout adolescence and add to a growing body of work showing that racial discrimination can undermine mental health and well-being among Black youth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Direct and Indirect Effects of Socioeconomic Status and Discrimination on Subjective Cognitive Decline: A Longitudinal Study of African American Women.

OBJECTIVES: The present study builds on recent findings suggesting that the stress of institutional and interpersonal racism may contribute to African Americans' elevated risk for dementia. We investigated the extent to which 2 consequences of racism-low socioeconomic status (SES) and discrimination-predict self-reported cognitive decline (SCD) 19 years later. Further, we examined potential mediating pathways that might link SES and discrimination to cognitive decline. Potential mediators included depression, accelerated biological aging, and onset of chronic illnesses. METHODS: Hypotheses were tested using a sample of 293 African American women. SCD was assessed using the Everyday Cognition Scale. Structural equation modeling was used to assess the effects of SES and racial discrimination, both measured in 2002, on SCD reported in 2021. Turning to the mediators, midlife depression was assessed in 2002, accelerated aging in 2019, and chronic illness in 2019. Age and prodrome depression were included as covariates. RESULTS: There were direct effects of SES and discrimination on SCD. In addition, these 2 stressors showed a significant indirect effect on SCD through depression. Finally, there was evidence for a more complex pathway where SES and discrimination accelerate biological aging, with accelerated aging, in turn leading to chronic illness, which then predicted SCD. DISCUSSION: Results of the present study add to a growing literature indicating that living in a racialized society is a central factor in explaining the high risk for dementia among Black Americans. Future research should continue to emphasize the various ways that exposure to racism over the life course effects cognition.

Changes in Loneliness, BDNF, and Biological Aging Predict Trajectories in a Blood-Based Epigenetic Measure of Cortical Aging: A Study of Older Black Americans.

A recent epigenetic measure of aging has developed based on human cortex tissue. This cortical clock (CC) dramatically outperformed extant blood-based epigenetic clocks in predicting brain age and neurological degeneration. Unfortunately, measures that require brain tissue are of limited utility to investigators striving to identify everyday risk factors for dementia. The present study investigated the utility of using the CpG sites included in the CC to formulate a peripheral blood-based cortical measure of brain age (CC-Bd). To establish the utility of CC-Bd, we used growth curves with individually varying time points and longitudinal data from a sample of 694 aging African Americans. We examined whether three risk factors that have been linked to cognitive decline-loneliness, depression, and BDNFm-predicted CC-Bd after controlling for several factors, including three new-generation epigenetic clocks. Our findings showed that two clocks-DunedinPACE and PoAm-predicted CC-BD, but that increases in loneliness and BDNFm continued to be robust predictors of accelerated CC-Bd even after taking these effects into account. This suggests that CC-Bd is assessing something more than the pan-tissue epigenetic clocks but that, at least in part, brain health is also associated with the general aging of the organism.

School Disengagement Predicts Accelerated Aging among Black American Youth: Mediation by Psychological Maladjustment and Moderation by Supportive Parenting.

Early experiences of school disengagement may serve as a warning sign for later young adult adjustment difficulties and eventually contribute to accelerated aging among Black American youth. At the same time, supportive parenting may play a protective role. Using longitudinal data from the Family and Community Health Study (FACHS), we examined psychological maladjustment (comprising depression, lack of self-regulation, and low self-esteem) as a mediator of the relationship between school disengagement and accelerated aging. We also examined the effect of supportive parenting in buffering the impact of school disengagement on adulthood outcomes by controlling for covariates. Hypotheses were examined in a sample of 386 (Mean age = 28.68; Females = 62.7%; Males = 37.3%) Black American youth who were followed into young adulthood. Path modeling was used to test hypothesized relationships. We found school disengagement, i.e., problems with school attendance, performance, and engagement, reported across ages 10-18, predicted psychological maladjustment, which, in turn, predicted accelerated aging at age 29. We also found a buffering effect for supportive parenting. No significant gender difference in the indirect effect or buffering effect was found. This study highlights the potential importance of greater attention to school disengagement to identify and potentially influence long-term health trajectories and adult outcomes for Black American youth.

Unstable Childhood, Adult Adversity, and Smoking Accelerate Biological Aging Among Middle-Age African Americans: Similar Findings for GrimAge and PoAm.

Objectives: The recent biological clocks GrimAge and PoAm are robust predictors of morbidity and mortality. Little research, however, has investigated the factors that influence their ticking speed. No study has used multivariate analyses to examine whether childhood adversity, adult hardship, lifestyle practices, or some combination of these factors best explains acceleration of these indices. Methods: Using a sample of 506 middle-age African Americans, the present study investigated the extent to which childhood instability, adult adversity, and lifestyle predict accelerated GrimAge and PoAm. Results: The two clocks were highly correlated and the pattern of findings was very similar for the two measures. Childhood instability, adult financial hardship, and smoking were significant predictors of both clocks. Discussion: The findings support a life course perspective where both the long arm of childhood as well as later life conditions influence speed of aging. Similar results across the two clocks enhance confidence in the findings.

Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans.

Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.

Epigenetic and Proteomic Biomarkers of Elevated Alcohol Use Predict Epigenetic Aging and Cell-Type variation Better Than Self-Report.

Excessive alcohol consumption (EAC) has a generally accepted effect on morbidity and mortality, outcomes thought to be reflected in measures of epigenetic aging (EA). As the association of self-reported EAC with EA has not been consistent with these expectations, underscoring the need for readily employable non-self-report tools for accurately assessing and monitoring the contribution of EAC to accelerated EA, newly developed alcohol consumption DNA methylation indices, such as the Alcohol T Score (ATS) and Methyl DetectR (MDR), may be helpful. To test that hypothesis, we used these new indices along with the carbohydrate deficient transferrin (CDT), concurrent as well as past self-reports of EAC, and well-established measures of cigarette smoking to examine the relationship of EAC to both accelerated EA and immune cell counts in a cohort of 437 young Black American adults. We found that MDR, CDT, and ATS were intercorrelated, even after controlling for gender and cotinine effects. Correlations between EA and self-reported EAC were low or non-significant, replicating prior research, whereas correlations with non-self-report indices were significant and more substantial. Comparing non-self-report indices showed that the ATS predicted more than four times as much variance in EA, CDT4 cells and B-cells as for both the MDR and CDT, and better predicted indices of accelerated EA. We conclude that each of the non-self-report indices have differing predictive capacities with respect to key alcohol-related health outcomes, and that the ATS may be particularly useful for clinicians seeking to understand and prevent accelerated EA. The results also underscore the likelihood of substantial underestimates of problematic use when self-report is used and a reduction in correlations with EA and variance in cell-types.

Shifts in lifestyle and socioeconomic circumstances predict change-for better or worse-in speed of epigenetic aging: A study of middle-aged black women.

BACKGROUND: While numerous studies have documented the power of new generation epigenetic clocks to predict morbidity and mortality, research regarding the causes of variation in speed of epigenetic aging is in the early stages. To the extent that these epigenetic clocks are robust measures of biological aging, they should be sensitive to various nutritional, behavioral, ecological, and social factors that have been shown to affect health. OBJECTIVE: Investigate over an 11-year period the extent to which changes in socioeconomic stress and lifestyle predict changes in speed of epigenetic aging among a sample of middle-aged African American women. METHODS: Using data from the Family and Community Health Study, we investigated whether changes in socioeconomic stress, diet, smoking, exercise, alcohol consumption, and relationship status predict changes in speed of biological aging assessed with 3 s-generation epigenetic clocks: AccelGrimAge, DunedinPoAm, and AccelPhenoAge. The study was able to avoid the challenges associated with self-reports of diet and smoking by employing recently developed epigenetic measures. RESULTS: Changes in socioeconomic stress and diet were associated with changes in speed of biological aging as assessed by all three epigenetic clocks, and changes in smoking was related to changes in AccelGrimAge and DunedinPoAm. Analyses controlling for cell-type indicated that in large measure diet exerts its effect on aging through its impact on the immune system. CONCLUSIONS: These findings suggest that adoption of a healthy diet and reduction in the use of tobacco are related to a decrease in epigenetic aging, whereas increased pressure relating to income, housing and economic independence are associated with an increase in the speed of aging. These effects were especially strong for the two epigenetic clocks AccelGrimAge and DunedinPoAm. Overall, the results indicate that stress and lifestyle changes may, for better or worse, influence the "biological weathering" often experienced by middle-aged African American women.

Do Loneliness and Per Capita Income Combine to Increase the Pace of Biological Aging for Black Adults across Late Middle Age?

In a sample of 685 late middle-aged Black adults (M age at 2019 = 57.17 years), we examined the effects of loneliness and per capita income on accelerated aging using a newly developed DNA-methylation based index: the DunedinPACE. First, using linear, mixed effects regression in a growth curve framework, we found that change in DunedinPACE was dependent on age, with a linear model best fitting the data (b = 0.004, p < 0.001), indicating that average pace of change increased among older participants. A quadratic effect was also tested, but was non-significant. Beyond the effect of age, both change in loneliness (b = 0.009, p < 0.05) and change in per capita income (b = -0.016, p < 0.001) were significantly associated with change in DunedinPACE across an 11-year period, accounting for significant between person variability observed in the unconditional model. Including non-self-report indices of smoking and alcohol use did not reduce the association of loneliness or per capita income with DunedinPACE. However, change in smoking was strongly associated with change in DunedinPACE such that those reducing their smoking aged less rapidly than those continuing to smoke. In addition, both loneliness and per capita income were associated with DunedinPACE after controlling for variation in cell-types.

The effect of early discrimination on accelerated aging among African Americans.

OBJECTIVE: This study examined the role of depressive symptoms in mediating the relationship between early life experiences of racial discrimination and accelerated aging in adulthood for African Americans (i.e., prediction over a 19-year period, from ages 10 to 29) after adjusting for gender and health behaviors. METHOD: Longitudinal self-report data over 7 waves of data collection from the Family and Community Health Study were utilized. The sample included 368 African Americans with usable gene expression data to compute accelerated aging, as well as complete data on all self-report variables including racial discrimination (Schedule of Racist Events) and depression (Diagnostic Interview Schedule for Children-Version 4). Blood was collected by antecubital blood draws from participants at age 29. The proposed model was tested by path analysis. RESULTS: Findings revealed that high discrimination at ages 10-15 was associated with depression at ages 20-29 (ß = .19, p = .001), controlling for depression at ages 10-15, which, in turn, was related to accelerated cellular-level aging (ß = .11, p = .048) after controlling for gender, alcohol consumption, and cigarette use. The indirect effect of racial discrimination on aging through depression at ages 20-29 was significant (ß = .021, 95% confidence interval [.001, .057]), accounting for 32.3% of the total variance. CONCLUSION: These findings support research conceptualizations that early life stress due to racial discrimination lead to sustained negative affective states continuing into young adulthood that confer risk for accelerated aging and possibly premature disease and mortality in African Americans. These findings advance knowledge of potential underlying mechanisms that influence racial health disparities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).